Effects of erdosteine on cyclosporine-A–induced hepatotoxicity in rats

Abstract

Cyclosporine A (CsA) is a potent immunosuppressive agent used for organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains one of the major side effects. The use of antioxidants reduces the adverse effects of CsA. The aim of this study was to determine the protective effects of erdosteine on CsA-induced liver injury through tissue oxidant/antioxidant parameters and to evaluate light microscopic alterations in rat-liver tissues. Rats were randomly divided into four experimental groups: The control group received sunflower oil (2 mL/kg/day, per orally; p.o.), while the other groups were treated with CsA (25 mg/kg/day, p.o.) or erdosteine (10 mg/kg/day, p.o.) or CsA+erdosteine, respectively. Serum aspartate aminotransferase and alanine aminotransferase levels, tissue malondialdehyde and nitric oxide levels, and superoxide dismutase, glutathione peroxidase and catalase enzyme activities were measured. Histological examination was performed. CsA caused a significant deterioration in the hepatic function tests, morphology, and gave rise to severe oxidative stress in the liver. Erdostein significantly improved the functional and histological parameters and attenuated the oxidative stresss induced by CsA. Erdostein protects liver tissue against oxygen free radicals and prevents hepatic dysfunction and morphological abnormalities associated with chronic CsA administration.

In-depth Identification of Pathways Related to Cisplatin-induced Hepatotoxicity through an Integrative Method Based on an Informatics-assisted Label-free Protein Quantitation and Microarray Gene Expression Approach

“…A single oral dose of cyclosporine A in rats has been reported to induce marked hepatotoxicity, as well as antioxidant enzymes, including CAT and SOD2 (43). In addition, many studies have reported that drug toxicity is modulated by antioxidant enzymes (41,42).…”

Non-alcoholic fatty liver disease and psoriasis: So far, so near

“…Thus, in MTX users, FibroTest can accurately predict the presence of liver fibrosis and the Fibroscan significantly predict the absence of significant liver fibrosis [106] . CsA is a potent immunosuppressor used for organ transplantations and various autoimmune disorders; one of the most detectable side effects is hepatotoxicity [107] . Acitretin is a synthetic retinoid which could induce liver toxicity by impairing mitochondrial phosphorylation efficiency without affecting the membrane potential [108] .…”

Erdosteine ameliorates the harmful effects of ischemia-reperfusion injury on the liver of rats

“…Erdosteine also has an antiinflammatory effect which is mediated through the inhibition of LPS-induced NF-kB activation 4 . The hepatoprotective effects of erdosteine against acetaminophen-induced liver damage, cyclosporine-A-induced hepatotoxicity, experimental biliary obstruction, cisplatininduced hepatic oxidant injury, doxorubicininduced hepatotoxicity, and vancomycininduced oxidative stress in the rat liver have been shown in previous studies [5][6][7][8][9][10][11] . Erdosteine has beneficial effects on ischemia-reperfusion injury in various organs including lung, brain, kidney, intestines, ovaries, and spinal cord [12][13][14][15][16][17] .…”

“…The final result is a protective effect on tissues that reduces lipid peroxidation, neutrophil infiltration and cell apoptosis mediated by noxious agents 3,28 . The hepatoprotective effect of erdosteine has also been presented in many studies [5][6][7][8][9][10][11] . Saritas et al 5 investigated the efficacy of erdosteine usage in acetaminophen-induced liver damage and compared it with N-acetyl cysteine (NAC) in the treatment and prevention of liver toxicity due to acetaminophen overdose.…”

“…Erarslan et al 6 determined the protective effects of erdosteine on cyclosporine A-induced liver injury. Erdosteine was found to significantly improve the functional and histological parameters and attenuate the oxidative stress induced by cyclosporine A.…”