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The role of oxidants and proinflammatory cytokines in the pathogenesis of pneumonia caused by Staphylococcus aureus (S. aureus) has been demonstrated. The present study aims to investigate the protective effect of ethyl acetate extract (EtOAc) obtained from Usnea longissima (UL) against acute oxidative and inflammatory lung damage due to S. aureus infection in rats. Albino Wistar-type male rats were divided into three groups: Healthy (HG), S. aureus inoculated (SaG), and S. aureus inoculated + ULEtOAc administered (SUL). SaG (n = 6) and SUL (n = 6) group rats' left nostrils (excluding HG) were inoculated with 0.1 ml bacterial mixture. After 24 hours, ULEtOAc (50 mg/kg) was administered orally to the SUL group, and the same volume of normal saline was administered orally to the HG (n = 6) and SaG groups. This procedure was performed once a day for seven days. Levels of oxidant and antioxidant parameters such as malondialdehyde (MDA) and total glutathione (tGSH), as well as pro-inflammatory cytokine levels such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), were measured in removed lung tissues. Tissues were also examined histopathologically. Biochemical results showed that ULEtOAc significantly suppressed the increase of MDA, NF-κB, TNF-α, and IL-1β levels and the decrease of tGSH caused by S. aureus in lung tissue. S. aureus inoculation caused severe mononuclear cell infiltration in interstitial areas, severe lymphoid hyperplasia in bronchial-associated lymphoid tissue and severe alveolar edema, histopathologically. Treatment with ULEtOAc had an attenuating effect on these histopathological findings. Experimental results from this study suggest that ULEtOAc may be beneficial in treating S. aureus-induced oxidative and inflammatory lung damage.

Background: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats. Methods: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated. Results: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group. Conclusions: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.

Objectives: This study aims to evaluate the pharmacological role of indigo extract in accelerating the wound healing in a rat model. Methods: Female Sprague-Dawley rats were anesthetized with ketamine (30 mg/kg, i.p.) and the full thickness of the marked skin was then cut carefully and wounds were left undressed. Indigo extract (5%) in PBS was applied topically twice daily until healing was complete. A control group of rats was treated with povidone-iodide (Betadine®). Rats treated with phosphate buffer saline were used as a negative control group. The rate of wound healing was assessed daily. Histopathological examination of skin sections were qualitatively assessed by independent evaluators. The inflammatory and apoptotic markers were assessed in skin tissue homogenates using ELISA. Results: Histopathology data showed that applying indigo to skin wounds enhanced the healing process, resulting in a significant decrease in dermal inflammation in comparison to untreated rats. Topical application of indigo significantly increased antioxidant enzyme activities with reduced malondialdehyde (MDA) levels in wound tissues. The levels of matrix metalloproteases-2 and -9 were significantly lower with an accompanied increase in the level of TGF-β1 in skin tissues from rats treated with indigo compared to the control group treated with PBS. Conclusions: The antioxidant and anti-inflammatory properties of indigo leaf extract accelerate the healing of skin injuries.

The aim of this study was to assess 17-β-estradiol (E2) influence on sciatic nerve regeneration after injury followed by a repair with chitosan conduit in ovariectomized female rats. The study was performed in 2 groups (n = 16) of rats: OVChit - after excision of a fragment of the sciatic nerve, a chitosan conduit was implanted; OVChitE10 group - additionally to chitosan conduit, shape-memory terpolymer rods based on poly(L-lactide-co-glycolide- co-trimethylene carbonate) releasing 17-β-estradiol for 20 weeks were implanted. The mean number of regenerating axons and mean fiber area were significantly greater in 17-β-estradiol-treated animals. In this group, the infiltrate of leukocytes was diminished. The presence of 17-β-estradiol receptors alpha and beta in motoneurons in the spinal cord were discovered. This may indicate the location where 17-β-estradiol affects the regeneration of the injured nerve. Estradiol released from the terpolymer rods for 20 weeks could enhance, to some extent, sciatic nerve regeneration after injury, and diminish the inflammatory reaction. In the future, 17-β-estradiol entrapped in terpolymer rods could be used in the repair of injured peripheral nerves, but there is a need for further studies.

The first two objectives were to establish which stimulation parameters of kilohertz frequency alternating current (KHFAC) neuromodulation influence the effectiveness of pudendal nerve block and its safety. The third aim was to determine whether KHFAC neuromodulation of the pudendal nerve can relax the pelvic musculature, including the anal sphincter. Simulation experiments were conducted to establish which parameters can be adjusted to improve the effectiveness and safety of the nerve block. The outcome measures were block threshold (measure of effectiveness) and block threshold charge per phase (measure of safety). In vivo, the pudendal nerves in 11 male and 2 female anesthetized Sprague Dawley rats were stimulated in the range of 10 Hz to 40 kHz, and the effect on anal pressure was measured. The simulations showed that block threshold and block threshold charge per phase depend on waveform, interphase delay, electrode-to-axon distance, interpolar distance, and electrode array orientation. In vivo, the average anal pressure during unilateral KHFAC stimulation was significantly lower than the average peak anal pressure during low-frequency stimulation (p < 0.001). Stimulation with 20 kHz and 40 kHz (square wave, 10 V amplitude, 50% duty cycle, no interphase delay) induced the largest anal pressure decrease during both unilateral and bilateral stimulation. However, no statistically significant differences were detected between the different frequencies. This study showed that waveform, interphase delay and the alignment of the electrode along the nerve affect the effectiveness and safety of KHFAC stimulation. Additionally, we showed that KHFAC neuromodulation of the pudendal nerves with an electrode array effectively reduces anal pressure in rats.

The reactivating and therapeutic efficacy of two newly developed oximes (K305, K307) was compared with the oxime K203 and trimedoxime using in vivo methods The study determining percentage of reactivation of tabun-inhibited acetylcholinesterase in the peripheral as well as central nervous system (diaphragm, brain) in tabun-poisoned rats showed that the reactivating efficacy of both newly developed oximes is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime. The therapeutic efficacy of all oximes studied roughly corresponds to their reactivating efficacy. While the ability of the oxime K305 to reduce acute toxicity of tabun in mice is approaching to the therapeutic efficacy of trimedoxime, the ability of another novel bispyridinium oxime K307 to reduce acute toxicity of tabun is significantly lower compared to trimedoxime and the oxime K203. Thus, the reactivating and therapeutic efficacy of both examined newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

The numerous challenges and detrimental effects connected with the treatment of peptic ulcers in the world today calls for alternative attention. Ethnomedicinally, Dialium guineense pulp (DAGP) has numerous pharmacological activities. This study investigated the anti-ulcer activities of Dialium guineense pulp on gastric mucosa injury induced with aspirin in albino Wistar rats. DAGP extract was orally administered at doses of 250, 500 and 1000 mg/kg bw (mg per kg of the body weight) per day for 3 or 7 days followed by 400 mg/kg bw oral aspirin administration. Ulcer indices were determined, followed by a biochemical estimation of antioxidant enzymes using gastric mucosal tissue from the stomach. Student's t-test was used to compare significant differences among groups of animals at P ≤ 0.05. The results showed that Dialium guineense pulp caused a significant decrease (P ≤ 0.05) in the ulcer index in aspirin induced rats. This decrease in ulcer index is dose dependent and 1000 mg/kg bw per day caused the highest decrease in 7 days. The results showed a significant increase (P ≤ 0.05) in lipid peroxidation and a decrease (P ≤ 0.05) in antioxidant enzymes activities in the aspirin-induced ulcerated rats. Oral administration of DAGP increased antioxidant enzymes activities and decreased injury in the gastric mucosa in ulcer induced rats. Therefore, this study showed that DAGP exhibited anti-ulcer potential and that the gastrointestinal protection may be through the scavenging action of free radicals by its constituent antioxidants. Thus, Dialium guineense pulp has ameliorative medicinal potential for the curing of gastric disorders.

Dyslipidemias are lipid metabolism alterations that cause increased levels of serum lipoprotein, cholesterol, and triglycerides. These alterations are associated with a higher incidence of cardiovascular diseases and are a risk factor for atherosclerosis development. This study aimed to evaluate the effect of Rosmarinus officinalis essential oil (EORO, 100 mg/kg) and its nanoemulsion (NEORO, 500 µg/kg) on Triton and coconut saturated-fat-induced (CSF) dyslipidemias using Wistar rats. The phytochemical evaluation of EORO performed by gas chromatography-mass spectroscopy (GC-MS) revealed 1,8-cineole (33.70%), camphor (27.68%), limonene (21.99%), and α-pinene (8.13%) as its major compounds. Triton-induced dyslipidemia significantly increased total cholesterol, LDL, and triglycerides levels. On the other hand, the groups treated with EORO and NEORO had significantly reduced total cholesterol, LDL, and triglycerides compared to the group treated only with Triton. Similar results were observed on the positive control treated with simvastatin. Dyslipidemia induced with coconut saturated-fat (CSF) caused abdominal fat gain, hypercholesterolemia, hypertriglyceridemia, increased LDL levels, and atherogenesis in the aorta. In contrast, the groups treated with EORO, NEORO, and simvastatin had significantly reduced hypercholesterolemia and hypertriglyceridemia, reduced abdominal fat gain, and absence of atherogenesis in the vascular endothelium. Overall, in the Triton-induced dyslipidemia model, EORO treatment had superior values than NEORO's (and simvastatin), although the differences were not too high, while in the CSF model, the values were mixed. In this manner, our results show an anti-dyslipidemic and anti-atherogenic activity effect by EORO and NEORO.

Bromobenzene is a compound which has contributed much in understanding the mechanisms involved in xenobiotic hepatotoxicity induced by drugs and environment pollutants. In the present study, the protective and ameliorative effect of beta-carotene was investigated against bromobenzene-induced hepatotoxicity and compared with silymarin, a standard hepatoprotective reference drug. Beta-carotene (10 mg/kg b.w. p.o.) was administered to the rats for 9 days before intragastric intubation of bromobenzene (10 mmol/kg b.w.). Liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), total protein content, bilirubin, total cholesterol, high-density lipoproteins, triglycerides, antioxidant status (reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase) were assessed along with histopathological analysis. ELISA was performed for analysing the levels of cytokines such as TNF-α, IL-1β and IL-6 in serum and in the liver. Caspase-3, COX-2 and NF-κB were evaluated by Western blotting. Administration of bromobenzene resulted in elevated levels of liver marker enzymes, bilirubin, lipid peroxidation and cytokines but deterioration in total protein content, antioxidant levels and histopathological conditions. Pre-treatment with beta-carotene not only significantly decreased the levels of liver markers, lipid peroxidation and cytokines but also improved histo-architecture and increased antioxidant levels minimising oxidative stress, and reduced factors contributing to apoptosis. This significant reversal of the biochemical changes on pre-treatment with beta-carotene in comparison with rats administered with bromobenzene clearly demonstrates that beta-carotene possesses promising hepatoprotective effect through its antioxidant, anti-inflammatory and antiapoptotic activity and hence is suggested as a potential therapeutic agent for protection from bromobenzene.

Background: The liver is the main metabolic organ involved in disposal and detoxification of various molecules. Plantago psyllium L. seed has been reported to exert positive effects in some pathological conditions. The current study aims to assess the hepatoprotective effect of Plantago psyllium L. seed extract against carbon tetrachloride-induced hepatotoxicity. Methods: Male albino Wistar rats were randomly divided into five groups of 10 rats each. Hepatotoxicity was induced by orally administered carbon tetrachloride (CCl4) for nine weeks with or without the different treatments which were utilized daily for the whole nine weeks. Serum and tissue samples were then withdrawn and different liver biomarkers were investigated. Results: Treatment of rats with Psyllium seed ethanolic extract significantly alleviated the toxic effects of CCl4. This was evidenced by its ability to restore liver biomarkers levels. Moreover, treatment with Psyllium seed extract normalized levels of oxidative biomarkers such as lipid peroxidation, hepatic content of reduced glutathione and catalase activity, as well as the expression level of the inflammatory marker TNF-α. Histopathological examination reflected the protective effect of the extract on liver architecture and confirmed the observed biochemical data. Conclusions: The presented data demonstrates a potential hepatoprotective effect of Psyllium seed extract compared to the standard hepatoprotective drug silymarin. This effect can be attributed to the antioxidant and anti-inflammatory effects of Psyllium extract.

The potency of two novel oximes (K920, K923) to reactivate tabun-inhibited acetylcholinesterase and to reduce acute toxicity of tabun was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited peripheral acetylcholinesterase (diaphragm) and central acetylcholinesterase (brain) in tabun-poisoned rats showed that the reactivating efficacy of both newly developed oximes is lower than the reactivating potency of the oxime K203 and trimedoxime. The therapeutic efficacy of both newly developed oximes roughly corresponds to their weak reactivating efficacy. Their potency to reduce acute toxicity of tabun in mice was lower compared to the oxime K203 and trimedoxime. All differences in reactivating efficacy of oximes and different protective ratios were found for selected doses of oximes used in this study. Based on the results obtained, we can conclude that the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning. The conclusion is only relevant for the experimental animals used in this study because of remarkable species differences in reactivating properties of oximes.

The ability of two newly developed oximes (K361, K378) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the oxime K203 and trimedoxime using a functional observational battery. The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (310 μg/kg i.m.; 90% of LD₅₀ value) were evaluated. Tabun-induced neurotoxicity was monitored by functional observational battery at 2 h following tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K361, K378) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime and the oxime K203. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime and obidoxime) in the treatment of acute tabun poisonings.

Aim: This study aimed to investigate the phenolic composition, antioxidant capacity, and toxicity of aqueous extracts of Calamintha nepeta L. leaves and their potential vasorelaxant effects. Methods: Aqueous extracts of Calamintha nepeta L. were prepared by three extraction methods: decoction, infusion, and maceration. The total phenolic contents of the extracts and their antioxidant properties were investigated. The toxicity was evaluated by Artemia salina lethality bioassay. The decoction extract was analyzed by HPLC for its chemical profile and was also used to evaluate the vasorelaxant effect on thoracic aortic rings isolated from healthy Sprague Dawley rats. Pre-contraction was induced by phenylephrine, followed by cumulative doses of the extract (0.001 up to 250 µg/ml). Results: Aqueous extracts of Calamintha nepeta L. showed noticeable radical scavenging and chelating activities. However, the decoction extract exhibited the most powerful antioxidant capacity. No toxicity was recorded for the extracts obtained by decoction and infusion. Caffeic acid, quercetin, and rosmarinic acid were the main identified compounds. Notably, the aqueous extract obtained by decoction induced significant relaxation in endothelium-intact aortic rings at lower concentrations, and at higher concentrations in denuded aortic rings. Conclusion: This study reveals that Calamintha nepeta L. extracted with a decoction method possesses potent antioxidant capacity and has an endothelium-dependent vasorelaxant effect.

The advanced glycated end products (AGEs) are formed in the diabetic patients; it is a major cause of macrovascular and microvascular complications in diabetes. Clinically there is no treatment available for the AGEs. Stveoside (Stv), a sweetener has potent anti-diabetic and anti-oxidant activity. Hence, we investigated its use in prevention of AGEs formation using in vitro and in vivo models. Diabetes was induced by streptozotocin (STZ). These rats were kept without treatment till blood HbA1c was markedly increased. They were then divided into 5 groups and treated orally with vehicle or Metformin (MET) or Stv respectively for 28 days. Every 7th day, animals were tested for body weight and blood glucose (BG). On the last day of treatment, all the groups were evaluated for physiological and biochemical parameters, histopathology and AGEs; N-carboxymethyl-lysine (CML) estimation. Stv showed inhibition of AGEs in in vitro as well as in in vivo respectively. Positive effects were seen on the BG, lipid profile and urine parameters as well it showed reduced formation of CML. It also showed antihyperglycaemic, antihyperlipedemic and nephroprotective activities. The present study provides scientific rationale for the use of Stv as a sweetener with additional benefits in diabetes.

Background and objectives: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. Methods: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. Results: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). Conclusion: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

The neuroprotective effects of a novel oxime KR-22934, the oxime K203 and obidoxime in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg i.m.; 80% LD₅₀) were studied. The tabun-induced neurotoxicity was monitored at 24 h following tabun challenge using a functional observational battery and an automatic measurement of motor activity. The results indicate that all tabun-poisoned rats treated with oximes in combination with atropine were able to survive within 24 h following tabun poisoning. One tabun-poisoned rat without antidotal treatment died within 24 h. The oximes KR-22934 and K203 combined with atropine showed a similar potency to decrease tabun-induced neurotoxicity at 24 h after tabun administration while the neuroprotective efficacy of obidoxime was slightly higher. However, no oxime was able to eliminate tabun-induced neurotoxicity completely. When atropine was administered alone, negligible neuroprotective efficacy was observed. Based on the results, a novel oxime KR-22934 did not bring any improvement of the neuroprotective efficacy of antidotal treatment of acute tabun poisonings.

Taurine (2-aminoethanesulfonic acid) is an organic acid widely distributed in animal tissues. It is involved in many physiological processes. Thus, it is widely discussed especially due to its antioxidant properties. In this study, we focused on the effect of taurine supplementation on the concentration of antioxidants in blood plasma and erythrocytes of Wistar rats. Taurine was applied in feed mixture in the dosage of 0, 1, 250, 500, 750, 1000, 1500, 2000, 2500, 3000, 3500 and 4000 mg/kg. We monitored both enzymatic and non-enzymatic antioxidants - glutathione peroxidase, glutathione reductase, and superoxide dismutase and reduced/oxidized glutathione and metallothionein. Using three different methods 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Ferric Reducing Antioxidant Power (FRAP) and free radicals, we determined antioxidant capacity. In addition, we monitored levels of uric acid and glucose. Our results revealed significant changes in both enzymatic and non-enzymatic parameters with the increasing taurine supplementation.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Background: Ginsenoside Rb2 is beneficial in cardiovascular disease treatment, yet its role in heart failure (HF) is obscure. This study aimed to investigate the effect and mechanism of ginsenoside Rb2 on HF. Methods: The left anterior descending branch-ligated HF rat model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9c2 cell model were constructed. Ginsenoside Rb2 were applied for intervention. Heart function indexes, miR-216a-5p expression, autophagy, oxidative stress, apoptosis, cell morphology, and proliferation were detected to explore the effect of ginsenoside Rb2 on HF. Overexpression of miR-216a-5p was employed to explore the specific mechanism of ginsenoside Rb2 on HF. Results: Ginsenoside Rb2 improved the heart function of HF rats, including the reduction of heart rate, LVEDP, and heart weight/body weight ratio, and the increase of LVSP, +dP/dtmax, -dP/dtmax, LVEF, and LVFS. It also down-regulated miR-216a-5p expression and enhanced OGD/R-induced cardiomyocyte viability. Ginsenoside Rb2 up-regulated Bcl2, LC3B II/I, and Beclin1, and down-regulated Bax, Caspase-3, and p62 in the myocardium of HF rats and OGD/R-induced H9c2 cells. Moreover, ginsenoside Rb2 increased the levels of SOD and CAT, but decreased the levels of MDA and ROS in the myocardium of HF rats and OGD/R-induced H9c2 cells. However, overexpression of miR-216a-5p promoted the apoptosis and oxidative stress of cardiomyocytes and inhibited autophagy, thus reversing the therapeutic effect of ginsenoside Rb2 on HF in vivo and in vitro. Conclusion: Ginsenoside Rb2 demonstrated potential as a therapeutic intervention for HF by enhancing autophagy and reducing apoptosis and oxidative stress through miR-216a-5p downregulation. Further research could explore its application in clinical trials and investigate the complex mechanism networks underlying its effects.

Oxidative stress (OS) is a major cause of hepatic and renal disorders, so present investigation was designed to evaluate the antioxidative efficacy of aqueous broccoli extract (BE) via three different doses - 10, 20 and 30 mmol - of glucosinolates against toxic effects of triazophos (TZ), an organophosphorous pesticide, in female rats during 30 days experiment. Six groups of rats were made and were orally intubated with TZ and BE as per experimental design. TZ and BE induced OS biomarkers of hepatic and renal toxicity - ALT, AST, urea and creatinine - were noticed in plasma, while catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), lipid peroxidation (LPO) were estimated in liver and kidney along with histological and apoptotic observation. Plasma ALT, AST, urea and creatinine levels along with organ OS parameters as CAT, SOD, GST and GPx were subtly improved in all BE + TZ treated rats. Decreased LPO and reduced apoptosis along with improved histoarchitecture was observed in all BE + TZ treated rats. Present study suggest that the administration of broccoli extract and TZ combination in rats can prevent severe alterations of hepatic and renal biochemical markers and disruptions of histological structure by antioxidative potential of BE from sprouts.

Aim
The current study was designed to investigate the effect of berbamine (BBM) on isoproterenol (ISO) induced changes in cardiac marker enzymes, myocardial oxidative stress, lipid profile and expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in male Wistar rats. Rats were pretreated with BBM (25 mg/kg) through intraperitoneal injection for 7 days followed by induction of myocardial infarction (MI) by subcutaneous injection of ISO (85 mg/kg) for last two days. Key findings: In the present study, the histopathological findings of the heart tissue showed that BBM treatment significantly minimized the damage induced by ISO. BBM pretreatment showed a significant decrease in heart weight, serum marker enzymes, lipid peroxidation and significant increase in cardiac endogenous enzymatic and non-enzymatic antioxidants compared to the ISO-treated group. In addition, we observed significantly upregulated eNOS expression and downregulated iNOS expression in BBM pretreated group. Thus, BBM protected the rat's heart from ISO-induced myocardial infarction by its antioxidant, and antilipidemic properties. Significance: The results of the present investigation suggested that BBM efficiently ameliorated the ISO-induced myocardial infarction in rats.

Purpose
Cadmium (Cd) is a classic cumulative nephrotoxicant and literature suggests that its toxicity is associated with oxidative stress and inflammation which contribute to pathologies in various tissues. We sought to investigate whether polyphenols isolated from virgin coconut oil (VCO) would modulate nephrotoxicity and inflammation induced by Cd in rats.
Methods
Rats were administered polyphenols prior to and along with Cd (5 mg/kg, orally) for 7 weeks. Serum markers of renal damage, interleukin-6 (IL-6), C-reactive protein (CRP) and nitric oxide (NO) were evaluated; renal activities of antioxidant enzymes, as well as malondialdehyde (MDA) and reduced glutathione (GSH) content were determined. Histopathologic alterations were evaluated to define kidney damage.
Results
Cadmium exposure induced nephrotoxicity and oxidative stress evident by significantly increased serum levels of creatinine, urea, and uric acid along with remarkable depression in renal activities of antioxidant enzymes and GSH with prominent increase in MDA. Inflammatory markers - IL-6, CRP and NO were significantly increased and confirmed by histopathology. Sub-chronic administration of VCO polyphenols attenuated the Cd-induced biochemical alterations compared to Cd control with remarkably improved histopathological observations.
Conclusion
The findings showed that VCO polyphenol supplementation protects against Cd-induced nephrotoxicity via its antioxidant and anti-inflammatory mechanisms in rats.

Pseuduvaria macrophylla (Family: Annonaceae) is commonly used as medicinal plant in Malaysia. A recent study with the Pseuduvaria species showed antioxidant and antidiabetic effects. This study aimed to ascertain antidiabetic potential of methanolic extract of Pseuduvaria macrophylla bark (PM) using streptozotocin-nicotinamide induced diabetic rat models. Various phytochemical and biochemical properties of the plant have been evaluated. The results showed that the extract has potentially normalized the elevated blood glucose levels by upregulating the insulin and C-peptide levels and alleviated oxidative stress by improving glutathione (GSH) and reducing lipid peroxidation (LPO) in the diabetic rats. In addition, PM has drastically downregulated the levels of pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathological examination of the pancreas in PM treated diabetic rats showed significant recovery of the pancreatic structural degeneration and thus reflected the protective role of PM against peroxidation damage by a rise in insulin level as evidenced by the immunohistochemistry study. The improved expressions of GLUT-1, GLUT-2 and GLUT-4 further confirmed the restoration of β-cell mass by PM. Interestingly, the findings demonstrated the antioxidant, anti-inflammatory and antihyperglycemic potential of PM which may provide future lead for the management of type-2 diabetes.

The potency of a novel oxime K203 in reactivating soman-inhibited acetylcholinesterase and reducing acute toxicity of soman was compared with commonly used oximes (HI-6, obidoxime, trimedoxime, methoxime) using in vivo methods. The study determining percentage of reactivation of soman-inhibited blood and tissue acetylcholinesterase in rats showed that the potency of the oxime K203 to reactivate soman-inhibited acetycholinesterase in the peripheral compartment is slightly higher than obidoxime and trimedoxime, especially in the diaphragm, slightly lower than methoxime and markedly lower compared to the oxime HI-6. The reactivating efficacy of the oximes studied in the peripheral compartment roughly corresponds to their potency to reduce acute toxicity of soman in mice. Based on the obtained data, we can conclude that the oxime K203 is not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute soman poisoning due to its relatively low potency to counteract acute toxicity of soman.

This study was designed to investigate effects of insulin on fracture healing and expression of vascular endothelial growth factor (VEGF) in diabetic rats. Wister rats were randomly divided into diabetic control (n=66), diabetic insulin (=66) and non-diabetic control group (n=66). Diabetes was established by peritoneal injection of alloxan. Tibia fracture was surgically created and was allowed to heal. Radiological and biomechanical examinations were performed on the healing tibia. Immuohistochemistry was used to assess VEGF expression in the healing fracture tissues. Cortical reconstruction of the fracture sites in non-diabetic control and diabetic insulin groups was more rapid than in diabetic control group within 6 weeks of the fracture. Mechanical strength of the affected tibia in the diabetic insulin and non-diabetic control group was superior to diabetic control group. Histological examination of the fracture sites revealed a delay in chondrocyte maturation and hypertrophy in diabetic control group. VEGF expression was widely distributed in fracture sites within the first 4 weeks in control and diabetic insulin treatment group. However VEGF expression in the callus and periosteum in diabetic control group was much less than in diabetic insulin or non-diabetic control group. In conclusion, diabetes delays fracture healing and adversely affects callus formation with a reduced VEGF expression at the fracture sites. Insulin therapy improves fracture healing in diabetes rats, possibly through enhancing VEGF expression in the fractured bones.

Objective
The aim of this study was to determine the effects of Shen-Fu injection treatment on skin flap survival in an experimental random pattern skin flap model in rats.
Materials and methods
Ninety male Sprague-Dawley (SD) rats were randomly assigned to the SFI-treated groups and normal saline-treated (control) group. SFI (10 or 20 ml/kg) or normal saline (10 ml/kg) were administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor α (TNF-α) and IL-6 were evaluated. Besides, flap survival rate, tissue edema, mean vessel densities, number of neutrophil, flap angiography and vascular endothelial growth factor (VEGF) expression were examined on day 7.
Results
Compared with the control group, the mean survival area in SFI groups were significantly larger showing a possible dose-dependent effect of SFI. SOD activity was increased significantly, as well as the VEGF expression. MDA level, in the test group, however, was decreased. The hematoxylin and eosin (H&E) stained slices revealed that SFI had the angiogenesis promotion effect, meantime inflammation was clearly inhibited in the SFI groups.
Conclusion
This study showed that intraperitoneally administered SFI significantly improved random skin flap survival in rats.

The aim of this study was to investigate the occurrence of toxic effects in liver tissue of rats treated with α-terpinene. All treatments were intraperitoneally administered at doses of 0.5, 0.75 and 1.0 ml kg^-1 during 10 days. Liver samples were collected and assessed by histopathological analysis, caspases -1, -3, -8 assay, biomarkers of hepatic damage and determination of oxidant/antioxidant status (thiobarbituric acid-reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione S-transferase (GST) and glutathione peroxidase (GPx)). Additionally, the cytotoxic and genotoxic effects were evaluated by comet assay. An increase was observed on TBARS levels and GPx activity on the hepatic tissue. Instead, CAT and SOD activities decreased in rats treated with a dose of 1.0 ml kg^-1 of α-terpinene. Concomitantly, ROS levels increased and GST levels decreased in rats treated with α-terpinene at doses of 0.5, 0.75 and 1.0 ml kg^-1. Also, there was an increase in frequency of damage, damage index and caspases, while cell viability decreased in rats treated with α-terpinene. Alanine aminotransferase and aspartate aminotransferase increased in rats treated with 1.0 ml kg^-1 of α-terpinene. Therefore, α-terpinene induces oxidative stress, cytotoxic and genotoxic effects in liver tissue involving the caspases activation.

Bacillary dysentery (shigellosis) continues to cause havoc worldwide, with a high infectivity rate. It causes bloody diarrhea, and around 99% of bacillary dysentery cases occur in developing countries. The objective of this study is to develop a polyherbal formulation with the scientific rationale in treating infectious bacillary dysentery disease. The anti-bacterial activity, the minimum inhibitory concentration of the formulation against bacillary dysentery, causing microbes like Shigella flexneri (MTCC 1457), Escherichia coli (MTCC 1687), and Salmonella enterica (MTCC 98), was analysed by well-diffusion method and broth dilution method, respectively. The biofilm inhibition activity was determined on 96 well polystyrene plates and anti-quorum sensing activity by Chromobacterium violaceum CV026. The cytotoxicity was examined by acute oral toxicity. Excreta and organ bacterial load were analyzed by serial dilution method. The formulation efficacy was determined by analyzing the blood sample of rats. The antimicrobial efficacy of the developed formulation was calculated by measuring the zone of inhibition which was found to be 24 mm, 25 mm, and 25 mm, and the MIC values of 1.5 mg/ml, 1.5 mg/ml, and 2.0 mg/ml against S. flexneri, S. enterica, E. coli, respectively. The results show that the polyherbal formulation significantly reduced biofilm formation and has anti-quorum sensing activity. The formulation also effectively decreases the bacterial load and increases the K+, Na+, and Ca++ ions in animals treated with the formulation. The developed formulation was found to be non-toxic and effective against bacillary dysentery; thus, it can be used for treating bacillary dysentery and related complications.

Purpose
Investigation of the effect of exercise and zinc (Zn) supplementation on trace element status in rats.
Methods
24 male Wistar were divided into four groups: control, exercised, Zn-supplemented (15 mg/kg weight Zn asparaginate), exercised Zn-supplemented. Zn was supplemented as Zn asparaginate. Serum lactate and creatinine levels, and creatine kinase activity were assessed. Tissue trace elements were estimated using inductively coupled plasma mass spectrometry.
Results
Exercise significantly increased lactate, and creatinine levels. Exercise significantly decreased muscle, kidney, and hair Zn; liver, muscle and serum Co; serum Fe; myocardial and hair Cu; liver, heart, skeletal muscle and kidney Se levels. Oppositely, exercise results in elevation of liver Zn; heart and skeletal muscle, kidney and hair Fe; kidney Cu; liver and hair Mn; serum and hair Se content. Zn supplementation reduced exercise-induced increase in lactate and creatinine levels, and elevated liver, kidney, heart, and hair Zn content in exercised rats. Supplementation with Zn reversed exercise-induced decrease in Co levels and increased Fe and Se stores in animals with high physical activity.
Conclusions
Beneficial effect of zinc supplementation in exercised organism may be associated not only with modulation of zinc status but regulation of other essential trace elements status and their biological effects.