Oxidative Stress In Rats Research Articles

Eel Oil Attenuates Acetaminophen-Induced Acute Liver Injury Through Inhibition of Oxidative Stress in Rats

Health practitioners all over the world have studied liver injury caused by drug side effects. Excessive production of free radicals causes cell damage, which has implications for pathological conditions in both humans and animals. Omega-3 fatty acids are a component of fish that can work as hepatoprotective agents. Eel (Anguilla bicolor) is known to contain omega-3 including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study aimed to evaluate the hepatoprotective activity of eel oil on rats via inhibiting oxidative stress. Methods: Acetaminophen-induced male Wistar rats were used as liver injury experimental models. Rats were divided into 5 groups, namely normal control, negative control, positive control (silymarin, 100 mg/kg), and two groups of eel oil dose (2000 mg/kg and 4000 mg/kg). The study was conducted for 14 days. The levels of serum glutamic pyruvic transaminase (SGPT), serum glutamic pyruvic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, albumin, Malondialdehyde (MDA), and glutathione (GSH) levels of the liver organ were measured. The data were analyzed using statistics and analysis of variance. Results: The study showed that eel fish oil can reduce SGPT and total bilirubin levels of male Wistar rats induced by acetaminophen. Eel oil at a dose of 4000 mg/kg could significantly reduce SGPT and liver bilirubin levels in male Wistar rats (p<0.05). Eel oil is effective in reducing malondialdehyde (MDA) levels and increasing glutathione (GSH) levels at a dose of 2000 mg/kg. Conclusion: Eel oil has hepatoprotective activity by inhibiting SGPT, total bilirubin, MDA, and increasing GSH levels in rats.

Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC). After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis. Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05). Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect.

English

Cisplatin is an efficacious anticancerous chemotherapeutic agent that is used to cure multiple types of malignancies. However, it has several hazardous effects on multiple organs, particularly liver. Tectochrysin is a naturally occurring flavonoid with extensive pharmacological properties. In this research, the potential anti-oxidant properties of tectochrysin against cisplatin-triggered oxidative stress in rats’ hepatic tissues were investigated. 48 male albino rats were separated into 4 groups: control cisplatin (10 mg/kg), cisplatin + tectochrysin (10 mg/kg + 5 mg/kg), and tectochrysin (5 mg/kg). The trial executed for one month. The biochemical, inflammatory, histopathological and liver markers were evaluated. The results of the research suggested that cisplatin treatment remarkably lowered the activities of glutathione (GSH), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GPx) as well as catalase (CAT) while escalated malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Cisplatin administered rats exhibited significantly higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) levels. Furthermore, cisplatin administration significantly elevated the inflammatory indicators i.e., interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) as well as nuclear factor kappa-B (NF- κB) and cyclooxygenase-2 (COX-2) activity along with histopathological impairments. Conversely, co-administration with tectochrysin effectively reversed the cisplatin-triggered impairments and abnormalities in the hepatic tissue of rats. The current investigation demonstrated that tectochrysin lowered cisplatin-induced hepatotoxicity owing to its antioxidant, reactive oxygen species scavenging activities and anti-inflammatory effects

Protective Effect of Tunisian Red Seaweed (Corallina officinalis) Against Bleomycin-Induced Pulmonary Fibrosis and Oxidative Stress in Rats.

Idiopathic pulmonary fibrosis is a chronic and progressive respiratory disease whose diagnosis and physiopathogenesis are still poorly understood and for which, until recently, there were no effective treatments. Over the past few decades, many studies have demonstrated that marine macroalgae such as red seaweeds are potential alternative sources of useful bioactive compounds possessing various physiological and biological activities. The present study was aimed to investigate the effect of Corallina officinalis aqueous extract (COAE) against bleomycin (BLM)-induced lung fibrosis in rat. Thus, Wistar rats were divided into 4 groups of 10 each: control, BLM (2mg/kg), BLM/COAE-150mg/kg and BLM/COAE-300mg/kg once a day for 21 days. Obtained results showed that COAE is rich in phenolic compounds and exhibited relatively high antioxidant activity. COAE might significantly reduce the damage caused by BLM by rewarding the decline in weight and pulmonary index in rats given only BLM. Moreover, lungs, liver and kidneys lipid peroxidation, and sulfhydryl group levels were reversed significantly in a dose-dependent manner in the COAE-treated groups. BLM decreased superoxide dismutase (SOD) and catalase (CAT) activities, while COAE administration increased the antioxidant enzyme activities. Histopathologically, COAE attenuates the severity of the inflammatory lungs state caused by instillation of BLM in rats. These findings suggest that COAE can be a potential therapeutic candidate against BLM-induced lung fibrosis.

Effects of Calocybe indica Mushroom on Oxidative Stress and Hematological ‎Alterations in Rats with Testosterone-induced Experimental Benign Prostatic ‎Hyperplasia

This study was designed to evaluate the protective effect of Calocybe indica extract (CLE) on testosterone propionate (TP)-induced hematological changes and oxidative stress in rats. The rats were grouped into six equal groups of ten rats each as follows:(a) control, (b) TP 3 mg/kg only, (c) 3mg/kg TP+ 5 mg/kg finasteride, (d) 3 mg/kg TP+250 mg/kg CLE, (e) 3 mg/kg TP+ 500 mg/kg CLE and (f) 3 mg/kg TP+1000 mg/kg CLE. The rats were administered TP subcutaneously for 28 days to induce benign prostatic hyperplasia (BPH) and simultaneously administered three graded doses of CLE, and finasteride as the standard drug. Hematological parameters, lipid peroxidation, antioxidant enzyme activities and histopathological examination of the prostate were assessed. BPH induction showed higher red blood cells (RBCs) count, haemoglobin (Hb) concentration, packed cell volume (PCV), serum prostate specific antigen (PSA), malondialdehyde (MDA) and lower white blood cell (WBC) count, lymphocyte count as well as lower catalase (CAT) and superoxide dismutase (SOD) activities. The simultaneous oral administration of CLE with testosterone injection did not significantly lower RBC count, Hb concentration and PCV but significantly lowered serum PSA and MDA. There was also a significantly higher WBC count, lymphocyte count, CAT and SOD activities. The results from this study suggest that dietary consumption of Calocybe indica, a mushroom with high antioxidant activity ameliorated BPH induced oxidative tissue damage and hematological alterations.

Paraquat-induced systemic inflammation and oxidative stress in rats improved by Curcuma longa ethanolic extract, curcumin and a PPAR agonist

The effect of Curcuma longa (Cl) ethanolic extract, nano-curcumin (Cu) and a PPARγ activator, pioglitazone on inhaled paraquat (PQ)-induced systemic inflammation and oxidative stress was examined in the present study. Control rats were exposed to normal saline and PQ groups to 27 and 54 mg/m3 (PQ-L and PQ-H) aerosols. Nine other PQ-H groups were treated with Curcuma longa (Cl, 150 and 600 mg/kg/day), nano-curcumin (Cu, 2 and 8 mg/kg/day), pioglitazone (Pio, 5 and 10 mg/kg), low dose of Pio + Cl and Cu and dexamethasone (0.03 mg/kg/day) for 16 days after PQ exposure period (n = 8). Total and differential WBC counts, malondialdehyde (MDA) and TNF-α levels were increased but thiol, catalase (CAT), superoxide dismutase (SOD), IL-10 and IFN-γ levels were decreased in the blood in the both PQ groups (p < 0.05 to p < 0.001). Treatment with Dexa and both doses of Cl, Cu, and Pio improved all measured variables compared to the PQ-H group (p < 0.05 to p < 0.001). The improvements of most variables in the treated group with low dose of Pio + Cl and Cu were higher than the effects of three agents alone. Systemic inflammation and oxidative stress induced by inhaled PQ were improved by Cl, Cu and Pio. In addition, a synergic effect between Pio with those of Cl and Cu was shown, suggesting PPARγ mediated effects of the plant and its derivative Cu.

Effect of allyl isothiocyanate on oxidative stress in COPD via the AhR / CYP1A1 and Nrf2 / NQO1 pathways and the underlying mechanism

BackgroundChronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally. Oxidative stress affects various molecular mechanisms and is the main driving factor of COPD. Ally isothiocyanate (AITC) is an effective component of Semen Sinapis Albae, which has favorable effects for the treatment of COPD, but its mechanism has not been fully elucidated. PurposeThis study aimed to elucidate the antioxidant effect of AITC on COPD and its molecular mechanism, and preliminarily determine the role of AhR in the progression of COPD. Study DesignThe COPD rat model was established by smoking combined with intratracheal instillation of lipopolysaccharide. Different doses of AITC, positive control drug acetylcysteine, AhR inhibitor alpha-naphthoflavone, and agonist beta-naphthoflavone were administered by gavage. Human bronchial epithelial cells induced by cigarette smoke extract (CSE) were used in an in vitro model to explore the molecular mechanisms of AITC. MethodsThe effects of AITC on lung function and oxidative stress in rats were evaluated in vivo using the respiratory function test, white blood cell count, enzyme-linked immunosorbent assay, and histological staining. The changes in protein expression in the lung tissue were detected by immunohistochemistry and Western blotting. RT-PCR, western blotting, and immunofluorescence were used to explore the molecular mechanisms of AITC. Enzyme-linked immunosorbent assay, reactive oxygen species probing, and flow cytometry were used to determine the antioxidant effect of AITC. ResultsAITC can improve the lung function of rats with COPD, restore lung tissue structure, improve oxidative stress, reduce inflammation, and inhibit lung cell apoptosis. AITC reversed the upregulation of AhR and CYP1A1 and the down-regulation of Nrf2 and NQO1 in the lung tissues of rats with COPD. CSE stimulation can increase the expressions of AhR and CYP1A1 and decrease the expressions of Nrf2 and NQO1 in 16HBE cells, leading to severe oxidative stress and inflammatory response and, ultimately, apoptosis. AITC inhibited AhR and CYP1A1 expressions, induced Nrf2 and NQO1 expressions, promoted Nrf2 nuclear translocation, and improved CSE-induced toxicological effects. ConclusionAITC may improve lung oxidative stress by inhibiting the AhR / CYP1A1 and activating the Nrf2 / NQO1 pathways, thereby delaying the pathological progression of COPD.

Effects of photobiomodulation on oxidative stress in rats with type 2 diabetes mellitus.

The present study aimed to evaluate photobiomodulation effects on oxidative stress in type 2 diabetes mellitus (DM2). Thirty-one male Wistar rats were used and divided into 4 groups: group 1 - animals without diabetes mellitus 2 without laser 21 J/cm2 (C-SHAM), group 2 - animals with diabetes mellitus 2 without laser 21 J/cm2 (C-DM2), group 3 - animals without diabetes mellitus 2 with laser 21 J/cm2 (L-SHAM), group 4 - animals with diabetes mellitus 2 with laser 21 J/cm2 (L-DM2). The protocol was performed 5 days/week, for 6 weeks. The animals that received photobiomodulation had one dose irradiated at two spots in the right gastrocnemius muscle. Twenty-four hours after the last intervention, the animals were euthanized. Heart, diaphragm, liver, right gastrocnemius, plasma, kidneys, weighed, and stored for further analysis. In rats with DM2, photobiomodulation promoted a decrease in thiobarbituric acid reactive substance assay (TBARS) in plasma levels. On the other hand, photobiomodulation demonstrated an increase in non-protein thiol levels (NPSH) in the heart, diaphragm and gastrocnemius. Moreover, photobiomodulation produced in the heart, diaphragm and plasma levels led to an increase in superoxide dismutase (SOD). Interestingly, photobiomodulation was able to increase superoxide dismutase in rats without DM2 in the heart, diaphragm, gastrocnemius and kidneys. These findings suggested that 6weeks of photobiomodulation in rats with DM2 promoted beneficial adaptations in oxidative stress, with a decrease in parameters of oxidant activity and an increase in antioxidant activity.

Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats

To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP). Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks, after which the rats with normal feeding were randomized into control group and acute pancreatitis (AP) group (n=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (n=6). In AP, HTGP, and honokiol groups, AP models were established by intraperitoneal injection of cerulean; in honokiol group, the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection. Serum TG, IL-6, and TNF-α levels were measured 24 h after the treatments, and pathological changes in the pancreas were observed with HE staining; The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH) were measured, and SIRT3 and manganese superoxide dismutase (MnSOD2) expressions were detected using Western blotting and immunohistochemistry. Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria. Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level (P < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-α, and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2, with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria. In rats with HTGP, honokiol treatment significantly decreased serum levels of IL-6, TNF-α, and MDA, increased GSH level and SIRT3 and MnSOD2 expressions, reduced ROS production, and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas. Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.

N-Acetylcysteine Decreases Myocardial Content of Inflammatory Mediators Preventing the Development of Inflammation State and Oxidative Stress in Rats Subjected to a High-Fat Diet.

Arachidonic acid (AA) is a key precursor for proinflammatory and anti-inflammatory derivatives that regulate the inflammatory response. The modulation of AA metabolism is a target for searching a therapeutic agent with potent anti-inflammatory action in cardiovascular disorders. Therefore, our study aims to determine the potential preventive impact of N-acetylcysteine (NAC) supplementation on myocardial inflammation and the occurrence of oxidative stress in obesity induced by high-fat feeding. The experiment was conducted for eight weeks on male Wistar rats fed a standard chow or a high-fat diet (HFD) with intragastric NAC supplementation. The Gas-Liquid Chromatography (GLC) method was used to quantify the plasma and myocardial AA levels in the selected lipid fraction. The expression of proteins included in the inflammation pathway was measured by the Western blot technique. The concentrations of arachidonic acid derivatives, cytokines and chemokines, and oxidative stress parameters were determined by the ELISA, colorimetric, and multiplex immunoassay kits. We established that in the left ventricle tissue NAC reduced AA concentration, especially in the phospholipid fraction. NAC administration ameliorated the COX-2 and 5-LOX expression, leading to a decrease in the PGE2 and LTC4 contents, respectively, and augmented the 12/15-LOX expression, increasing the LXA4 content. In obese rats, NAC ameliorated NF-κB expression, inhibiting the secretion of proinflammatory cytokines. NAC also affected the antioxidant levels in HFD rats through an increase in GSH and CAT contents with a simultaneous decrease in the levels of 4-HNE and MDA. We concluded that NAC treatment weakens the NF-κB signaling pathway, limiting the development of myocardial low-grade inflammation, and increasing the antioxidant content that may protect against the development of oxidative stress in rats with obesity induced by an HFD.

Origanum majorana L. extract alleviates dexamethasone-induced hepatotoxicity, oxidative stress and pathological alterations in vivo

BackgroundOriganum majorana (O. majorana) is one of the most widely used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, antimutagenic, anticoagulant and beneficial properties. Our study's main goal is to determine how well O. majorana leaf extract can reduce hepatotoxicity and oxidative stress produced by dexamethasone (DXM). Thirty female rats were divided into three groups of ten. Animals in group1 received distilled water daily for eight weeks and served as control. Those in group 2 exposed subcutaneously to 0.1 mg/kg body weight of DXM three times per week for eight weeks and served as the toxic group, while those in group 3 were treated daily and orally with 100 mg/kg of O. majorana aqueous extract + 0.1 mg/kg of DXM three times per week for eight weeks and served as treated group.ResultsDue to DXM treatment, the activities of liver function markers were significantly elevated (P < 0.0001), whereas O. majorana pretreated animals improved or reduced the elevated liver function enzyme activities. Dexamethasone administration considerably enhancing oxidative stress which rose (P < 0.0001) MDA concentration and attenuated the antioxidant defense system by decreasing the activities of GST, GSP, GSR, and CAT significantly in liver homogenate when compared to control animals. The results further demonstrated that pretreatment with O. majorana boosted the antioxidant defenses against the damaging effects of DXM.ConclusionIt can be said that dexamethasone exposure induced- hepatotoxicity and oxidative stress in rats that repaired by O. majorana aqueous extract which had the ability to reduce the impact of hepatic damage. To evaluate the health benefits and safety of O. majorana in individuals, more clinical research is needed.Graphical abstract

Stimulation of angiotensin II type 2 receptor attenuates organ injury in rats with polymicrobial sepsis.

Both inflammation and oxidative stress contribute to the pathogenesis of sepsis and its associated organ damage. Angiotensin-(1-7), acting through the Mas receptor and angiotensin II-type 2 receptors (AT2R), could attenuate organ dysfunction and improve survival in rats with sepsis. However, the role of AT2R in inflammation and oxidative stress in rats with sepsis is unclear. Therefore, this study examined the modulatory effects and molecular mechanism of AT2R stimulation in rats with polymicrobial sepsis. Male Wistar rats underwent cecal ligation and puncture (CLP) or sham surgery followed by the administration of saline or CGP42112 (a selective, high-affinity agonist of AT2R, 50 μg/kg intravenously) at 3 h after sham surgery or CLP. The changes in hemodynamics, biochemical variables, and plasma levels of chemokines and nitric oxide were detected during the 24-h observation. Organ injury was evaluated by histological examination. We found that CLP evoked delayed hypotension, hypoglycemia, and multiple organ injuries, characterized by elevated plasma biochemical parameters and histopathological changes. These effects were attenuated by treatment with CGP42112. CGP42112 significantly attenuated plasma chemokines and nitric oxide production and reduced liver inducible nitric oxide synthase and nuclear factor kappa-B expression. More importantly, CGP42112 significantly improved the survival of rats with sepsis (50% vs. 20% at 24 h after CLP, p < 0.05). The protective effects of CGP42112 may be related to anti-inflammatory responses, suggesting that the stimulation of AT2R is a promising therapeutic candidate for the treatment of sepsis.

Changes in the parameters of pro-oxidant–antioxidant balance in the brain of rats with stepwise incomplete cerebral ischemia

Objective: to evaluate the activity of oxidative stress in rats with stepwise incomplete cerebral ischemia (SICI). Material and methods. Experiments were performed on 24 male outbred rats weighing 260±20 g, allocated into 3 subgroups (6 animals in each) based on time of ligation of both common carotid arteries (CCA). The control group comprised of sham-operated rats of the same sex and similar weights (n=6). To identify the pro-oxidant–antioxidant state of the brain based on its homogenates, the activity of lipid peroxidation processes, the content of thiobarbituric acid reactive substances (TBARS), the concentration of reduced glutathione (GSH), total thiol groups (TSH), and the activity of glutathione peroxidase were determined. Results. SICI with ligation interval of both CCAs of 1 day and 3 days led to a significant decrease in the total SH groups of proteins and glutathione by 30% (p=0.038) and 46% (p=0.044), respectively, TBARS concentration by 29% (p=0.038) and 31% (p=0.043), respectively. SICI with the maximum interval between CCA ligations was manifested by less pronounced changes in the pro-oxidant–antioxidant state of the brain. Conclusion. In SICI with ligation of both CCAs 7 days apart, at which histological changes were the least pronounced, changes in the pro-oxidant–antioxidant balance were insignificant. The most pronounced disorders of the pro-oxidant–antioxidant balance in the brain were observed in the subgroup with the minimum interval between CCA ligations, which implied the highest activity of oxidative stress.

The effects of swimming exercise and detraining on hemorheological parameters and oxidative stress in rats with metabolic syndrome

BackgroundModerate-intensity aerobic exercise training with high frequency is recommended in metabolic syndrome (MetS). We aimed to investigate the effects of swimming and subsequent detraining on hemorheology and oxidative stress in MetS. Material and methodsA total of 80 rats were used. MetS was induced by a 4mg/g monosodium glutamate (MSG) injection to rats on days 0–10, every other day. Swimming exercise training was applied 30minutes, 3 days/week, with a 5% body weight load, for 18 weeks. Detraining was applied for 8 weeks. Erythrocyte deformability was measured with an ektacytometer, whole blood viscosity (WBV) by a cone-plate viscometer, total oxidant-antioxidant capacity (TOS-TAS) were measured by commercial kits. ResultsExercise resulted in an increment of HDL in rats with MetS, which was not reversed by detraining. Swimming decreased HOMA-IR score in MetS. Detraining caused an increase in WBV in healthy rats. The exercise applied resulted in an increase in TAS in both healthy and MetS rats. ConclusionWe suggest that swimming may be beneficial in MetS and may contribute positively to the prevention of the development of possible complications by increasing TAS. Since some of the gains of exercise training are reversed by detraining, lifetime exercise training may be recommended.

Effect of leaf extract and fractions of Solanum anomalum on oxidative stress markers, kidney function indices and histology of alloxan-induced diabetic rats

In ethnomedicine, the leaf of S. anomalum is used to treat a variety of illnesses, including diabetes. The goal of this study was to assess the effects of S. anomalum leaf extract and fractions on the kidney function indices, renal histology, and indicators of oxidative stress in rats with diabetes caused by alloxan. Antioxidative stress and renoprotective potentials of leaf extract (70-210 mg/kg) and fractions (140 mg/kg) were assessed by determining oxidative stress markers levels, kidney function parameters and histopathology of alloxan-induced diabetic rats. The levels of oxidative stress indicators (Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and glutathione (GSH) in the kidney were significantly increased by the leaf extract and fractions (p&lt;0.05–0.001), while the level of MDA was lowered in the treated diabetic rats. The high serum levels of urea and creatinine in diabetic rats were significantly (p&lt;0.05–0.001) reduced by the leaf fractions, whereas the levels of electrolytes were not significantly decreased . The kidney histology of the treated diabetic rats either showed no pathological abnormalities or a considerable reduction in pathological features. The findings suggest the antioxidative stress and nephroprotective capabilities of Solanum anomalum leaf extract and fractions, which may be a result of the antioxidant activities of their phytochemical constituents

Hypobaric hypoxia induced renal injury in rats: Prophylactic amelioration by quercetin supplementation.

The present study aims at assessing the effect of hypobaric hypoxia induced renal damage and associated renal functions in male SD rats. Further, this study was extended to explore the protective efficacy of quercetin in ameliorating the functional impairment in kidneys of rats under hypobaric hypoxia. Rats were exposed to 7620m (25000 ft.) at 25°C ±2 in a simulated hypobaric hypoxia chamber for different time durations (0h,1h, 3h, 6h, 12h, 24h and 48h) in order to optimize the time at which maximum renal damage would occur. The rats were exposed to hypoxia for 12h duration was considered as the optimum time, due to significant increase in oxidative stress (ROS, MDA) and renal metabolites (creatinine, BUN and uric acid) with remarkable reduction (p<0.001) in antioxidants (GSH) in plasma, as compared to other tested durations. Moreover, these findings were in support with the histopathology analysis of renal tissues. For optimum quercetin dose selection, the rats were administered with different doses of quercetin (25mg, 50mg, 100mg and 200mg/Kg BW) for 12h at 7620 m, 25°C ±2, 1h prior to hypoxia exposure. Quercetin 50mg/kg BW was considered as the optimum dose at which significant (p<0.001) reduction in oxidative stress levels followed by reduction in creatinine and BUN levels were obtained in plasma of the rats compared to hypoxia control rats. Quercetin prophylaxis (50mg/kg BW) stabilized the HIF-1α protein expression followed by reduced VEGF protein expression along with reduced levels of LDH (p<0.001) in the kidneys of rats compared to hypoxia control. Histopathological observations further substantiated these findings in reducing the renal tissue injury. The study findings revealed that, quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced renal injury by reducing the oxidative stress in rats.

Medicago sativa ameliorated cyclophosphamide-induced thrombocytopenia and oxidative stress in rats

Effect of Medicago sativa (MS) hydro-ethanolic extract against the cyclophosphamide (CP)-induced toxicity was evaluated in rats grouped as: Control; CP (100 mg/kg subcutaneous, day 1–3); and CP+ MS100, 200, and 400 mg/kg/day, orally for 14 days. Hematologic, lipid, hepatic and oxidative stress markers were analyzed. Platelet, WBC, RBC, Hb and Hct in the CP group were lower than the control. The MS200 and MS400 groups had lower lipids, liver enzymes, nitrite and malondialdehyde levels but higher platelet, WBC, thiol, superoxide dismutase and catalase levels than the CP group. MS ameliorated CP-induced thrombocytopenia, oxidative stress, and increases in serum lipids and hepatic enzymes.

Nano-hesperetin ameliorates 6-hydroxydopamine-induced behavioral deficits and oxidative damage by up-regulating gene expression of antioxidant enzymes.

Hesperetin (Hst) has shown several pharmacological effects. The efficacy of Hst is highly restricted in vivo due mainly to poor bioavailability. This investigation was intended to compare the influence of Hst and nano-Hst treatment on 6-hydroxydopamine (6-OHDA)-induced behavioral deficits and oxidative stress in rats. Forty-two Wistar male rats were equally assigned to 6 groups: control, 6-OHDA, Hst5, Hst10, nano-Hst5, and nano-Hst10. Treatment with Hst and nano-Hst was initiated 1 day after the intrastriatal injection of 6-OHDA and continued for 28 days. Behavioral deficits were evaluated using apomorphine-induced rotation test (AIRT), narrow beam test (NBT) and novel object recognition test (NORT), and the hippocampus and striatum were used to evaluate oxidative stress-related parameters. The rats injected only with 6-OHDA showed learning and memory deficits but Hst and nano-Hst treatments improved it (p<0.001). Compared to the control group, a marked promotion in Malondialdehyde (MDA) levels along with a marked reduction in activities and gene expression of antioxidant enzymes and reduced glutathione (GSH) levels in the hippocampus and striatum were observed in the 6-OHDA group (p<0.01). However, administration of Hst and nano-Hst remarkably diminished MDA levels (p<0.01), and significantly increased the activities (p<0.01) and gene expression of antioxidant enzymes (p<0.05) and GSH levels (p<0.01) compared to the 6-OHDA group. In most parameters, nano-Hst has shown better therapeutic effects than Hst. Our findings reveal that Hst can be considered as a potential candidate for the treatment of neurodegenerative diseases and that nano-Hst may have better bioavailability.

Melatonin Supplement Plus Exercise Effectively Counteracts the Challenges of Isoproterenol-Induced Cardiac Injury in Rats.

To explore the combined effects of exercise and melatonin supplement against the challenges of isoproterenol-induced cardiac oxidative stress and injury in rats., the expression of peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α), mitochondrial biogenesis, and adenosine triphosphate (ATP) was up-regulated in cardiac muscle in normal rats and in a melatonin and exercise regimented group. Cardiac injury was induced by two subcutaneous injections of isoproterenol in the rats. The combination of exercise and melatonin supplement successfully counteracted the isoproterenol-induced cardiac injury, which is reflected by the improved hemodynamic parameters, reduction in oxidative stress markers, and cardiac injury serum markers (cardiac troponin-I and creatine kinase-MB). The cardiac tissue level of ATP, expression of PGC-1α and mitochondrial biogenesis-related genes, mitochondrial membrane potential, and the activities of typical antioxidants (glutathione, superoxide dismutase) were preserved, whereas the levels of reactive oxygen species, lipid peroxidation, and inflammatory cytokines were suppressed in the melatonin and exercise regimented (MEI) group compared to the group treated with isoproterenol alone. Furthermore, the expression of endoplasmic reticular stress- and apoptosis-related proteins (Bax, Bcl2, and caspase-3) was also effectively suppressed in the MEI group. Therefore, the present study suggests that melatonin supplement in combination with exercise prevents cardiac injury, possibly through the preservation of mitochondrial function and inhibition of oxidative stress in rats.

Nephroprotective Effect of Fennel (Foeniculum vulgare) Seeds and Their Sprouts on CCl4-Induced Nephrotoxicity and Oxidative Stress in Rats

Functional and nutritional characteristics of seed sprouts and their association with oxidative stress-related disorders have recently become a focus of scientific investigations. The biological activities of fennel seeds (FS) and fennel seed sprouts (FSS) were investigated in vitro and in vivo. The total phenolic content (TPC), total flavonoids (TF), total flavonols (TFF), and antioxidant activity (AOA) of FS and FSS were examined. HPLC and GC-MS analyses for FS and FSS were carried out. Consequently, the nephroprotective and antioxidative stress potential of FS and FSS extracts at 300 and 600 mg kg-1 on CCl4-induced nephrotoxicity and oxidative stress in rats was investigated. In this context, kidney relative weight, blood glucose level (BGL), lipid profile, kidney function (T. protein, albumin, globulin, creatinine, urea, and blood urea nitrogen (BUN)), and oxidative stress biomarkers (GSH, CAT, MDA, and SOD) in the rat's blood as well as the histopathological alteration in kidney tissues were examined. Results indicated that the sprouting process of FS significantly improved TPC, TF, TFL, and AOA in vitro. HPLC identified nineteen compounds of phenolic acids and their derivatives in FS. Thirteen phenolic compounds in FS and FSS were identified, the highest of which was vanillic acid. Six flavonoids were also identified with a predominance of kaempferol. GC-MS indicated that the trans-anethole (1-methoxy-4-[(E)-prop-1-enyl]benzene) component was predominant in FS and FSS, significantly increasing after sprouting. In in vivo examination, administering FS and FSS extracts ameliorated the BGL, triglycerides (TG), total cholesterol (CHO), and their derivative levels compared to CCl4-intoxicated rats. A notable improvement in FS and FSS with 600 mg kg-1 compared to 300 mg kg-1 was observed. A dose of 600 mg FSS kg-1 reduced the TG, CHO, and LDL-C and increased HDL-C levels by 32.04, 24.62, 63.00, and 67.17% compared to G2, respectively. The atherogenic index (AI) was significantly improved with 600 mg kg-1 of FSS extracts. FS and FSS improved kidney function, reduced malondialdehyde (MDA), and restored the activity of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Both FS and FSS extracts attenuated the histopathological alteration in CCl4-treated rats. Interestingly, FSS extract presented better efficiency as a nephroprotection agent than FS extract. In conclusion, FSS can potentially restore oxidative stability and improve kidney function after acute CCl4 kidney injury better than FS. Therefore, FS and FSS extracts might be used for their promising nephroprotective potential and to help prevent diseases related to oxidative stress. Further research on their application in humans is highly recommended.