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This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF- α , and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells' infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver., Competing Interests: The authors declare that no conflict of interest exists in the submission of this manuscript., (Copyright © 2021 Rasha A. Hassan et al.)

The effect of gamma-irradiation and ionizing radiation (high-energy electrons beam) on the physicochemical properties of metoprolol tartrate at the solid phase and aqueous solution, has been investigated in the present study to model some properties affected by absorbed doses and to reveal some interesting mutual causal correlation. The proposed some interesting models can be adapted to other experimental conditions, and the newly obtained values of the adjustable parameters could be an excellent criterion of the state quality of the metoprolol tartrate or for other additional interpretations. The peculiar behaviour of variation of physicochemical properties against dose leads us to confirm the suggested optimized doses mentioned in previous work, for sterilization and safe medical uses.

Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers.

Background: The pyrethroid class of insecticides, including deltamethrin, is being used as substitutes for organochlorines and organophosphates in pest-control programs because of their low environmental persistence and toxicity. This study was aimed to investigate the impact of commonly used pesticides (deltamethrin) on the blood and tissue oxidative stress level in catfish (Clarias gariepinus); in addition to the protective effect of α-tocopherol on deltamethrin induced oxidative stress. Catfish were divided into three groups, 1st control group include 20 fish divided into two tanks each one contain 10 fish, 2nd deltamethrin group, where Fish exposed to deltamethrin in a concentration (0.75 μg/l) and 3rd Vitamin E group, Fish exposed to deltamethrin and vitamin E at a dose of 12 μg/l for successive 4 days.Serum, liver, kidney and Gills were collected for biochemical assays. Tissue oxidative stress biomarkers malondialdhyde (MDA) and catalase activity in liver, kidney and gills tissues, serum liver enzymes (ALT and AST), serum albumin, total protein, urea and creatinine were analysed., Results: Our results showed that 48 h. exposure to 0.75 μg/l deltamethrin significantly (p < 0.05) increased lipid peroxidation (MDA) in the liver, kidney and gills while catalase activity was significantly decreased in the same tissues. This accompanied by significant increase in serum ALT, AST activity, urea and creatinine and a marked decrease in serum albumin and total proteins., Conclusions: It could be concluded that deltamethrin is highly toxic to catfish even in very low concentration (0.75 μg/l). Moreover the effect of deltamethrin was pronounced in the liver of catfish in comparison with kidneys and gills. Moreover fish antioxidants and oxidative stress could be used as biomarkers for aquatic pollution, thus helping in the diagnosis of pollution. Administration of 12 μg/l α-tocopherol restored the quantified tissue and serum parameters, so supplementation of α-tocopherol consider an effective way to counter the toxicity of deltamethrin in the catfish.

Aims: This study aimed to examine the effect of high fat diet (HFD) to modulate brain dysfunction, and understand the linkages between obesity, metabolic disturbances and the brain oxidative stress (BOS) dysfunction and modulation with hydroxyl citric acid of G. Cambogia., Methods: Rats were divided into 3 groups; 1st control, maintained on standard normal rat chow diet, 2nd HFD, maintained on high fat diet along 12 week and 3rd HFD+G, administered G. Cambogia for 4 weeks and each group include 8 rats. Blood, brain and abdominal fat were collected for biochemical measurements., Results: HFD group showed significant increase in energy intake, final BW and BW gain. Also significant increase in weight of abdominal fat in HFD group. HFD induce metabolic disturbance through increasing the lipid profile (LDL, TG, TC), γGT and α-amylase activity, uric acid level and hyperglycemia, while decreasing creatine kinase (CK) activity.These changes associated with lowering in brain nitric oxide (NO) level and rising in serum butyrylcholinesterase (BChE), brain catalase activity and MDA levels as oxidative stress markers. These alterations improved by G. Cambogia that decrease BOS and increased NO level., Conclusions: Rats fed HFD showed, metabolic disturbances produce hyperglycemia, hypertriglyceridemia, hypercholesterolemia and increased LDL associated with increased BOS. Involvement of BuChE, NO and oxidative stress associated with metabolic disturbances in the pathophysiological progression in brain, suggesting association between obesity, metabolic disorders and brain alteration while, using G. Cambogia, ameliorate the damaging effects of the HFD via lowering feed intake and BOS.

Objective: The objective of the present study was to determine the ability of cerium oxide (CeO(2)) nanoparticles to protect against monocrotaline (MCT)-induced hepatotoxicity in a rat model., Method: Twenty male Sprague Dawley rats were arbitrarily assigned to four groups: control (received saline), CeO(2) (given 0.0001 nmol/kg intraperitoneally [IP]), MCT (given 10 mg/kg body weight IP as a single dose), and MCT + CeO(2) (received CeO(2) both before and after MCT). Electron microscopic imaging of the rat livers was carried out, and hepatic total glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) enzymatic activities were quantified., Results: Results showed a significant MCT-induced decrease in total hepatic GSH, GPX, GR, and GST normalized to control values with concurrent CeO(2) administration. In addition, MCT produced significant increases in hepatic CAT and SOD activities, which also ameliorated with CeO(2)., Conclusions: These results indicate that CeO(2) acts as a putative novel and effective hepatoprotective agent against MCT-induced hepatotoxicity.

Background: Obesity became major health problem in the world, the objective of this work was to examine the effect of high sucrose and high fat diet to induce obesity on antioxidant defense system, biochemical changes in blood and tissue of control, non treated and treated groups by administration of Garcinia cambogia, and explore the mechanisms that link obesity with altered renal function., Methods: Rats were fed a standard control diet for 12 week (wk) or a diet containing 65% high sucrose (HSD) or 35% fat (HFD) for 8 wk and then HFD group divided into two groups for the following 4 wks. One group was given Garcinia+HFD, the second only high fat, Also the HSD divided into two groups, 1st HSD+Garcinia and 2nd HSD. Blood and renal, mesenteric, Perirenal and epididymal adipose tissues were collected for biochemical assays., Results: HFD and HSD groups of rats showed a significant increase in feed intake, Body weight (BW) and body mass index (BMI). Also there were significant increases in weights of mesenteric, Perirenal and epididymal adipose tissues in HFD and HSD groups.HFD and HSD affect the kidney by increasing serum urea and creatinine levels and decreased level of nitric oxide (NO) and increased blood glucose, low density lipoproteins (LDL), triacylglycerol (TG), total cholesterol (TC) and malondialdehyde (MDA). Glucose 6-phosphate dehydrogenase (G6PD) activities were significantly decreased in HFD while there were significant increases in HSD and HSD+G groups p ≤ 0.05 compared with control. Moreover, renal catalase activities and MDA levels were significantly increased while NO level was lowered. These changes improved by Garcinia that decreased the oxidative stress biomarkers and increased NO level.There were significant positive correlations among BMI, kidney functions (Creatinine and urea), TG and Oxidative markers (renal MDA and catalase)., Conclusions: Rats fed a diet with HFD or HSD showed, hypertriglyceridemia, increased LDL production, increased oxidative stress and renal alteration. Moreover, suggesting association between lipid peroxidation, obesity and nephropathy, while Garcinia ameliorated the damaging effects of the HFD or HSD and decreased feed intake, MDA level and decreased oxidative stress in renal tissues.

Objective: We aimed to examine the changes in serum insulin and leptin levels in induced type 1 diabetes mellitus in relationship to glycemic state and lipid profiles and to clarify the role of lipoic acid (LA)., Methods: Ninety-six male rats were equally divided into the following: a control group (normal, nondiabetic), a diabetic group induced by subcutaneous injection of alloxan (non-LA-treated), and an LA-treated diabetic group (for 4 weeks). Body weight, serum lipid profile, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and leptin were measured., Results: This study showed a significant increase in serum triacylglycerol (TG), total cholesterol, glucose levels, and HOMA-IR and a significant decrease in body weight gain, insulin, and leptin levels in the diabetic group compared to the control group. LA treatment induced a significant decrease in glucose, TG, and total cholesterol levels and significantly increased serum insulin and leptin levels in comparison with the diabetic group., Conclusion: Induced diabetes resulted in insulin resistance, hyperlipidemia, and hypoleptinemia, while LA ameliorates these changes and improves insulin sensitivity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity., Aim: To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats., Method: White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks.Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed., Results: Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR) significantly increased in HFD in comparison with the control group. The treatment with L-carnitine or HMF improved the condition. HFD elevated hepatic MDA and lipid peroxidation associated with reduction in hepatic GSH and catalase activity; whereas administration of L-carnitine or herbal extract significantly ameliorated these hepatic alterations., Conclusion: HFD induced obesity associated with a disturbed lipid profile, defective antioxidant stability, and high values of IR parameters; this may have implications for the progress of obesity related problems. Treatment with L-carnitine, or HMF extract improved obesity and its associated metabolic problems in different degrees. Also HMF has antioxidant, hypolipidaemic insulin sensitizing effects. Moreover HMF might be a safe combination on the organs whose functions were examined, as a way to surmount the obesity state; and it has a distinct anti-obesity effect.

To investigate the effects of atorvastatin and cinnamon on serum lipid profile, oxidative stress, antioxidant capacity, hepatic enzymes activities, nitric oxide (NO) as well as homocysteine (Hcy) in hypercholesterolemic rats, 48 male albino rats, weighing 130-190 gm were divided into 2 groups, normal group fed on basal rat chow diet (n=12) and high cholesterol group (HCD) were fed on 1% cholesterol-enriched diet for 15 day (n=36). Hypercholesterolemic rats were divided into 3 subgroups (n=12 for each) fed the same diet and treated with atorvastatine (HCD+Atorvastatin) or cinnamon extract (HCD+cinnamon) or none treated (HCD) for 3&6 weeks. Serum triglycerides (TG), Total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), ALT, AST, NO, Hcy, hepatic reduced glutathione (GSH), Malondialdehyde (MDA) and antioxidant enzymes, Superoxide dismutase (SOD) and catalase activity were measured. Results showed that HCD increased significantly TG, TC, LDL-C, ALT, AST, Hcy and hepatic MDA, while lowered significantly antioxidant enzyme activities and NO levels. Atorvastatin therapy significantly increased HDL-C, NO and antioxidant activity while decreased LDL-C, MDA and Hcy concentrations. Serum TG, TC, LDL-C, ALT, AST and hepatic MDA levels were significantly lowered meanwhile, serum HDL, NO values and hepatic antioxidant activities were significantly, higher in cinnamon-treated than untreated group. These results indicate that lipid abnormalities, oxidative injury and hyperhomocystienemia were induced by HCD and this study recommend that administration of atorvastatine or cinnamon provided protection against the lipemic-oxidative disorder and act as hypocholesterolemic, hepatoprotective agent and improve cardiovascular function through modulation of oxidative stress, NO and Hcy.