Methylseleninic Acid and Grape Seed Extract Alleviate Tamoxifen Induce Hepatotoxicity in Rats
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The current study aimed to evaluate the hepatoprotective potential of methylseleninic acid (MSA) and grape seed extract on tamoxifen-induce hepatotoxicity in female rats.
Adult female Sprague-Dawely rats were randomly allocated into: control, dimethylsulfoxide (DMSO), Tam (30 mg/kg, for 10 days), GSE (600 mg/ kg), MSA (0.2 mg/kg) and GSE+MSA groups. Alanine aminotransferase (ALT) activity, malondialdehyde (MDA), reduced glutathione (GSH), catalase activity, nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected. Histopathological examination of the liver and immunohistochemical staining of caspase-3 were performed.
Tamoxifen-induced liver injury in rats was successfully established. Tamoxifen significantly elevated hepatic catalase activity, MDA, nitric oxide contents, serum IL-6 and TNF-α levels. It significantly reduced serum ALT activity and hepatic protein content and significantly increased caspase-3 expression in the hepatic tissue. In addition, fatty changes, inflammatory cells infiltration and apoptosis were detected.
Administration of GSE or MSA as single protective treatment resulted in restoring serum ALT and hepatic catalase activities to their normal values. Single MSA restored hepatic MDA, NO and total protein contents to their normal values while GSE restored serum IL-6. Combined pre-treatment induced hepatoprotective effect, reversed all variables significantly to the normal levels. While rats’ liver pretreated with single GSE or MSA showed weak positive caspase-3 expression, combined pre-treatment rats showed absence of caspase- 3 expression as normal rats and exhibited normal liver architecture.
The results indicate significant modulatory effects of GSE and MSA combined treatment in overcoming and preventing the observed hepatotoxic adverse effects of tamoxifen.
KeywordsTamoxifen Hepatic injury Methylseleninic acid Grape seed extract
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