Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats

Abstract

Although Doxorubicin (DOX) is a widespread drug used in the treatment of cancer, its clinical use is restricted due to its common side effects. In addition, administrating DOX with an antioxidant has recently become a new strategy in preventing the side effects of DOX. The protective effects of morin, a natural flavonoid, against DOX-induced liver and kidney damage in rats were investigated biochemically, immunohistochemically and histopathologically in this study. The experimental procedure was planned as 10 days, and 5 groups consisting of seven rats were formed. Morin was given orally to rats at a dose of 50 and 100 mg/kg for 10 days and DOX was given a single dose of 40 mg/kg intraperitoneally on day 8. In order to determine the protective effect of morin against oxidative stress caused by DOX, reduced glutathione (GSH) and malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activities were measured in liver and kidney tissues. Liver and kidney tissue damage were determined both histopathologically and by serum alanine transaminase (ALT), aspartate transaminase (AST), urea and creatinine analysis. In order to determine the effect of DOX-induced inflammation and against the effect of morin, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor kappa B (NF-κB) levels were determined in both tissues. Liver and kidney B-cell lymphoma-2 (Bcl-2) levels were determined biochemically. In addition, Bax expression in liver tissue and aquaporin-2 (AQP-2) and nephrin expression in renal tissue were determined immunohistochemically. It was determined that oxidative damage caused by DOX decreased and improvement of liver and kidney function markers were observed in the groups that were treated with morin. In addition, pre-treatment of morin showed a regulatory effect on TNF-α, IL-1β and NF-κB levels. It prevented the increase in DOX-induced Bax expression and decrease in Bcl-2 level, AQP-2 and nephrin expression. Histopathological examination revealed that it prevented tissue damage in liver and kidney tissues. © 2019 Elsevier B.V.