(-)-Epigallocatechin gallate (EGCG) pharmacokinetics and molecular interactions towards amelioration of hyperglycemia, hyperlipidemia associated hepatorenal oxidative injury in alloxan induced diabetic mice.

Diabetes mellitus has become a serious problem associated with health complications, such as metabolism disorders and liver-kidney dysfunction. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study was conducted to evaluate the hypoglycemic, antilipidemic, and antioxidant effects of EGCG in surviving diabetic mice. Alloxan diabetic mice were treated with EGCG. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglycerides, urea, creatinine, and transaminases. Their livers and kidneys were isolated to assess oxidative damage and to perform histological analysis. Both EGCG and insulin treatment of diabetic mice resulted in a significant reduction in fasting blood glucose levels. EGCG supplementation also ameliorated hepatic as well as renal toxicity indices. Moreover, diabetic mice injected with EGCG exhibited significant changes in antioxidant enzyme activities in the liver and kidney. Histological analyses also showed that it exerted an ameliorative action on these organs and efficiently protected the liver-kidney functions of diabetic mice. EGCG was found to bind α-amylase, PTP1B, and α-glucosidase with good affinities ranging from -6.1 to -8.4 kcal/mol. The findings revealed that EGCG administration induced attractive curative effects on diabetic mice, particularly in terms of liver-kidney function. EGCG can, therefore, be considered as a potential strong candidate for future applications to treat and alleviate diabetic burden. Its pharmacokinetics, high affinities, and molecular interactions with the targeted receptors satisfactory explain the in vivo findings.

Protective Effects of A. sativa against Oxidative Stress-Induced Liver Damage in Ovariectomized Mice.

Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg-1 d-1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 µg kg-1 d-1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.

Potential protective effects of the edible alga Arthrospira platensis against lead-induced oxidative stress, anemia, kidney injury, and histopathological changes in adult rats.

Oxidative damage has been proposed as a possible mechanism involved in lead toxicity. This study investigated the possible protective effect of dietary Arthrospira platensis supplementation against lead acetate-induced kidney injury in adult male rats. Rats were divided into 4 groups: normal rats (control rats), rats treated with spirulina, rats treated with lead (Pb) (0.344 g/kg body weight), and rats treated with Pb and spirulina. The exposure of rats to Pb for 30 days provoked renal damage with significant increases in hematological parameters, oxidative stress-related parameters (i.e., thiobarbituric acid reactive substances, protein carbonyl content, advanced oxidation protein products, and hydrogen peroxide), creatinine and urea levels in plasma, and uric acid level in urine. Conversely, antioxidant enzyme activities (i.e., catalase, glutathione peroxidase, and superoxide dismutase) and levels of nonprotein thiols, plasma uric acid, and urinary creatinine and urea decreased. The administration of spirulina to Pb-treated rats significantly improved weight, peripheral blood parameters, oxidative stress-related parameters, renal biomarker levels, and antioxidant enzyme activities. Also, rats treated with Pb and spirulina had normal kidney histology. These healing effects are likely the result of the high phenol content and significant antioxidant capacity of A. platensis. Our data strongly suggest that spirulina supplementation improves kidney function and plays an important role in the prevention of complications of Pb intoxication.

Potential immunomodulatory and antioxidant effects of walnut Juglans regia vegetable oil against lead-mediated hepatic damage and their interaction with lipase activity in rats.

Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor-α (TNF-α), caspase-3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL-Ch, LDL-Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near-normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.

Effects of co-exposure to lead and zinc on redox status, kidney variables, and histopathology in adult albino rats.

Lead (Pb) is a toxic metal that induces a wide range of biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in Pb toxicity. The current study was carried out to evaluate the antioxidant activities of zinc (Zn) supplement against lead acetate-induced kidney injury in rats. In this study, adults male rats were treated for 15 days with Pb (0.344 g/kg body weight (bw)) associated or not with Zn (10 mg/kg bw). Our study showed that supplementation with Zn prevented renal dysfunction as indicated by plasma biomarkers (urea, uric acid, creatinine, lactate dehydrogenase, and alkaline phosphatase levels) and oxidative stress-related parameters (thiobarbituric acid reactive substances, protein carbonyl, advanced oxidation protein product, superoxide dismutase, catalase, glutathione peroxidase, and vitamins (A, E)) in kidney tissue. The corrective effect of Zn on Pb-induced kidney nephrotoxicity recovered normal kidney histology. Overall, this study indicates that Zn alleviated the toxic effects of this heavy metal on renal tissue, suggesting its role as a potential antioxidant and nephroprotective agent.

Ameliorated Effects of (-)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats.

The aim of the study was to assess the protective effect of (-)-epigallocatechin gallate (EGCG), a flavonoid abundant in green tea, against ammonium metavanadate (AMV)-induced oxidative stress in male Wistar rats. Four groups of animals have been used, a control group and three test groups. In the first test group, AMV was intra-peritoneally (i.p) injected daily (5 mg/kg body weight for five consecutive days). The second test group of animals was also injected daily with EGCG (5 mg/kg body weight) during the same period. However, the third test group was i.p. injected with both AMV and EGCG (5 mg/kg body weight for five consecutive days). When given alone, AMV induced an oxidative stress evidenced by an increase of lipid peroxidation levels (expressed as TBARS concentration) in kidney. In these animals, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were significantly decreased, suggesting significant reduction of the antioxidant defense system at the cell level. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In AMV-treated animals receiving EGCG, the oxidative stress was much less pronounced and activities of antioxidant enzymes were kept close to control values. Histopathological changes were less prominent. Our results confirm that green tea and other sources of flavonoids might confer a strong protection against ammonium metavanadate-induced oxidative stress.

The protective effect of Malva sylvestris on rat kidney damaged by vanadium.

BACKGROUND: The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay. RESULTS: In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats. CONCLUSION: Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds.

[Impact of green tea on oxidative stress induced by ammonium metavanadate exposure in male rats]. / Impact du thé vert sur l'effet oxydatif du métavanadate d'ammonium chez le rat male pubère.

Transitional metals, as vanadium, are known to exert noxious effects by generating oxidative stress. Addition of antioxidants in the diet could decrease the cytotoxic effect related to the oxidative stress. The present study, carried out in Wistar rats, is a contribution to the evaluation of protective effects of green tea Camellia sinensis, which is known to be rich in antioxidant compounds (polyphenols...). Rats were divided into four groups: (C) was control, (V) was given ammonium metavanadate (AMV), (TH) was given herbal tea as drink (66 g/l) and TH + V was given tea and metavanadate. Group (TH) was given herbal tea one month before vanadium treatment. Metavanadate was daily i.p. injected (5 mg NH4VO3/kg body weight) for 10 days. (C) and (TH) groups received i.p. injections of 0.9% NaCl during the same period. Changes in lipid peroxidation levels (TBARS) in kidney, liver and testes, serum concentrations of vitamins E and A and superoxidismutase (SOD) and catalase (CAT) activities in blood cells were determined. One month pre-treatment with green tea, followed by 10 days of treatment (TH) did not change TBARS in liver and testes as compared to controls, but induced a clear decrease of TBARS in kidneys. Intraperitoneal administration of AMV to rats (V) induced a time-dependant increase of TBARS in kidney, liver and testes that was lowered in rats (V + TH) drinking tea. Vitamin E concentrations were found to be drastically decreased from day 1 to 10 in rats (V). Vitamin A concentration was decreased at day 10 only. Drinking tea lowered AMV inhibitory effects in rats (V + TH), and conversely an increase of vitamins A and E concentrations were found at day 10. SOD and catalase activities were found increased in the blood cells from day 1 to day 5 and conversely decreased at day 10. In contrast, associated to green tea, AMV did not affect SOD and catalase activities compared to controls.