stilbenes and ferric-nitrilotriacetate

The influence of melatonin, curcumin, quercetin, and resveratrol pretreatment on ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage was studied. Male Wistar rats were treated orally once daily for 3 days with melatonin (10 mg/kg), curcumin (50 mg/kg), quercetin (15 mg/kg), and resveratrol (10 mg/kg). One hour after the last dose of antioxidants, a single dose of Fe-NTA was administered (8 mg of Fe/kg body weight, i.p.) to pre-treated animals. Twenty-four hours after Fe-NTA administration, the lipid peroxidation (LP), reduced glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in kidney homogenates. Iron, zinc, and copper concentrations were estimated in kidney tissue. Administration of Fe-NTA to rats induced renal LP (170%, P < 0.001) and inhibited catalase (78%, P < 0.05) in the kidney. The oral pretreatment with melatonin, curcumin, quercetin, and resveratrol each one was effective in decreasing the Fe-NTA-induced LP (P < 0.001); however, it did not influence the FeNTA-induced inhibition of renal CAT activity. No changes were found in renal GSH level and GSH-Px activity compared to control animals. The pretreatment with antioxidants did not affect the increase in renal iron content, blood urea nitrogen/creatinine ratio, and relative kidney weight of FeNTA-intoxicated rats. The results indicate that the pretreatment with natural antioxidants, curcumin, melatonin, quercetin, and resveratrol, significantly and equally suppressed lipid peroxidation induced by Fe-NTA but had no effect on other markers of FeNTA nephrotoxicity and iron deposition in kidneys.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Catalase; Curcumin; Disease Models, Animal; Ferric Compounds; Glutathione; Glutathione Peroxidase; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Melatonin; Metals, Heavy; Nitrilotriacetic Acid; Organ Size; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Resveratrol; Stilbenes

Oxidative stress is associated with liver fibrosis in vivo and with hepatic stellate cell (HSC) activation in vitro, but the intracellular mechanisms mediating these effects are mostly unknown. The Na+/H+ exchanger plays a key role in regulating the cell cycle, and is involved in HSC proliferation. Its role in different HSC features, such as collagen accumulation, is still unknown. We thus evaluated if the Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat HSC.. HSC were incubated with 0.1 mM ferric nitrilotriacetate complex (FeNTA). Intracellular hydroperoxides and malonildialdehyde (MDA) levels in the culture media were measured by the dichlorofluorescein and TBARS method, respectively. Intracellular pH and Na+/H+ exchanger activity were measured using the fluorescent dye BCECF. Cell proliferation was measured by immunohistochemistry for bromodeoxyuridine incorporation. Collagen type I accumulation in the culture media was measured by ELISA.. HSC incubation with FeNTA resulted in a significant production of intracellular hydroperoxides and MDA, associated with increased Na+/H+ exchange activity and baseline intracellular pH (pHi). Exposure of HSC to FeNTA significantly enhanced the number of proliferating HSC and collagen type I levels in the culture medium. All these effects were reversed by the antioxidant resveratrol and by the Na+/H+ exchanger inhibitor amiloride.. This study indicates that the Na+/H+ exchanger might represent a common mediator of the different effects induced by oxidative stress on HSC. The reduction in cell proliferation and collagen synthesis induced by amiloride could represent a new therapeutic challenge in liver fibrosis.

Topics: Animals; Antioxidants; Carcinogens; Cell Cycle; Cell Division; Cells, Cultured; Collagen; Culture Media; Ferric Compounds; Fluoresceins; Fluorescent Dyes; Kinetics; Liver; Liver Cirrhosis, Experimental; Malondialdehyde; Nitrilotriacetic Acid; Oxidative Stress; Rats; Resveratrol; Sodium-Hydrogen Exchangers; Stilbenes; Thiobarbituric Acid Reactive Substances