Simvastatin attenuates chromium-induced nephrotoxicity in rats

Abstract

BackgroundHexavalent Chromium (Cr (VI)) compounds are extremely toxic and have been demonstrated to induce nephrotoxicity associated with oxidative stress in humans and animals. The wide environmental distribution of these agents lead to an increase interest of preventive effects of its adverse effects. ObjectivesThe propose of the present study was to determine the potential protective effects of simvastatin (SIMV) on Cr (VI)-induced nephrotoxicity in rat. Materials and MethodsForty-eight adult male Wistar rats (180-220 g BW) were randomly assigned to eight groups (n = 6). Group one received SIMV 20 mg/kg/day. Group two was given vehicle only. Groups three, five and seven received intraperitoneally (i.p) sodium dichromate (Cr (VI)) at doses of 8, 12 and 16 mg/kg body weight. Groups four, six and eight pretreated with the 20 mg/kg SIMV 30 minutes to prior administration of Cr (VI) at doses of 8, 12 and 16 mg/kg, respectively. The experiment repeated for eight consecutive days. Twenty-four hours after the last administration, animals were killed with overdose of sodium pentobarbital. Kidney tissues were excised for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological examination. ResultsChromium induced a dose dependent elevation of MDA and reduction of GSH levels. Histopathological manifestations were observed in Cr (VI)-treated rats. SIMV administration restored Cr (VI) produced biochemical and morphological changes in rat kidney. SIMV decreased MDA values and increased GSH levels in Cr (VI)-treated rats. SIMV clearly reversed the microscopic damage, demonstrating its protective effects against Cr (VI)-induced kidney injury. ConclusionsThis observation suggests that SIMV may have a protective effect against Cr (VI)-induced oxidative stress in rat kidney.

An Evaluation of Hepatotoxicity, Nephrotoxicity, and Genotoxicity Induced by Acute Toxicity of Hexavalent Chromium and Comparison of the Possible Protective Role of Selenium and Vitamin E on These Effects

“…Acute Cr(VI) toxic group revealed a significant increase in the level of liver malondialdehyde (MDA) as compared to the control group .Similar finding was reported by Goodarzi et al, (2016)and Hegazy et al, (2016) while Cengiz et al, (2016) observed that the level of MDA had not changed in K2Cr2O7 treated rats as compared to the control group.…”

“…In the present study, there were significant increase in superoxide dismutase (SOD) activity and significant decrease in the serum level of reduced glutathione (GSH) and catalase activity in acute Cr(VI) toxic group as compared to the control group similar to Goodarzi et al, (2016).However, Cengiz et al, (2016) observed that SOD, catalase and reduced GSH levels had not changed in K2Cr2O7 treated rats .…”

Atorvastatin prevents cadmium-induced renal toxicity in a rat model

“…Atorvastatin belongs to a class of statins with indicated antioxidant (10 mg/kg, for 10 days) (Pal et al, 2015), antithrombotic (10 mg/kg/day) (Ozbek et al, 2009), immune-modulatory (40 mg for 4 weeks) (Fuentes-Orozco et al, 2018), and antitumor effects in experimental animal models (Garjani et al, 2012). Atorvastatin at 20 mg/day decreased inflammation through HMG-CoA reductase inhibitors, lowered low-density lipoprotein (LDL) cholesterol in plasma, and promotion of antioxidant effects by suppressing oxidation pathways (Goodarzi et al, 2016; Wang et al, 2017). Atorvastatin is a reductase inhibitor and effective in altering lipid profiles, lipid peroxidation, and antioxidant systems (Yan et al, 2020).…”

Screening models of nephrotoxicity and their molecular mechanism

“…[76]Because heavy metals are excreted mostly through the kidneys, excess levels of hexavalent chromium [Cr (VI)] are accumulated there which causes nephrotoxicity. [77]Chromium has the ability to influence cellular functioning by blocking antioxidant enzymes and binding to antioxidant components such as Glutathione (GSH), contributing to oxidative stress. In, proximal convoluted tubules, chromium compounds are selectively deposited where they produce acute tubular necrosis in large dosages after parenteral administration.…”