Ameliorative role of curcumin on copper oxide nanoparticles-mediated renal toxicity in rats: An investigation of molecular mechanisms.

The increasing role of copper oxide nanoparticles (CuO NPs) in many industries and their broad range of applications increase its potential toxic effects. Curcumin possesses a wide range of health benefits. This study aimed to evaluate the role of curcumin in attenuating CuO NPs toxicity in rat kidney. Thirty six animals were divided into five groups; control groups (I, II), curcumin group orally received curcumin 200 mg/kg bw, CuO NPs group orally gavaged 250 mg/kg bw CuO NPs and combined group orally gavaged curcumin and CuO NPs. Treatment was given for 3 months. Administration of CuO NPs revealed elevation in serum creatinine and blood urea nitrogen levels, elevated kidney and urine levels of kidney injury molecule-1, decreased catalase, superoxide dismutase activities, total sulfhydryl, reduced glutathione content, increased serum reactive oxygen species, tissue total oxidant status, lipid hydroperoxides, protein carbonyl, malondialdehyde, nitric oxide levels, increased interleukin-1ß, tumor necrosis factor-α, nuclear factor (NF-κB), and decreased heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) genes expression. Moreover, histopathological alteration in kidney structure was detected. Immunohistochemical-stained sections by caspase-3 reaction revealed apoptosis. Pretreatment with curcumin improved most of the adverse effects in rats treated with CuO NPs regarding oxidative stress and inflammatory indices in kidney, and kept histopathological- and immunohistochemical-stained sections near to normal. This study shows that curcumin administration attenuates the toxicity in the kidney of CuO NPs-treated rats through its antioxidant, anti-inflammatory, and antiapoptotic effects.

The molecular mechanisms of lithium-induced cardiotoxicity in male rats and its amelioration by N-acetyl cysteine.

Lithium is one of the most powerful and commonly used medications for the treatment of various psychiatric diseases, especially bipolar disorder. However, it has a narrow therapeutic index with toxic effects on various organs. There are several case reports of lithium-induced arrhythmia and ischemia. The current work aimed to study the toxic effects of lithium on the heart of adult albino rats and its molecular mechanisms and the ameliorating effect of N-acetyl cysteine (NAC). Sixty adult male Wistar albino rats were classified into four groups; control, NAC-treated received NAC 500 mg/kg/week dissolved in 1 ml 0.9% sodium chloride intraperitoneal, lithium-treated received 52.5 mg/kg/day of lithium carbonate dissolved in 1 ml 0.9% sodium chloride orally by gavage, and lithium-and-NAC-treated (group IV) received lithium and NAC in the previous doses. After 12 weeks, the rats of group III showed a significant accumulation of ascites and a decrease in the mean arterial blood pressure and electrocardiographic (ECG) findings of ischemia and arrhythmia. In addition, there was an elevation in cardiac biomarkers creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and several histological lesions with a significant increase in the area % of Van Gieson, endothelial nitric oxide synthase (eNOS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreaction. There was significant upregulation of microRNA-1, microRNA-21 (miRNA-21), and microRNA-29 (miRNA-29). MiRNA-21 was strongly positively correlated to the area % of 8-OHdG, while miRNA-29 was strongly positively correlated to the area % of Van Gieson staining. NAC significantly improved the cardiotoxic effects of lithium. Being a nontoxic and safe antioxidant, NAC can be used to ameliorate lithium-induced cardiac injury.