Therapeutic Efficacy of Chrysoeriol on Doxorubicin-induced Liver Damage by Improving Biochemical and Histological Profile in Rats

Abstract

Doxorubicin (DOX) is a commonly prescribed, potent anti-cancer drug, however, its clinical administration is restricted due to its serious organotoxic potential especially hepatotoxicity. Chrysoeriol (CSR) is a natural flavonoid, which exhibits putative antioxidant and free-radical scavenging activities. This research was planned to assess the hepatoprotective potential of CSR against DOX-prompted hepatic damage in male albino rats. 48 rats were segregated into four group viz. Control, DOX-treated group (3 mgkg -1 ), DOX + CSR-treated group (3 mgkg -1 + 20 mgkg -1 ) and CSR-treated group (20 mgkg -1 ). DOX treatment induced liver toxicity as indicated by the significant elevation in the serum levels of alanine aminotransferase (ALT) alkaline phosphatase (ALP), and aspartate aminotransferase (AST). Additionally, DOX exposure disrupted the biochemical profile by decreasing the activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), glutathione reductase (GSR) and glutathione S-transferase (GST), while raised the levels of ROS and MDA. Furthermore, inflammatory markers level such as nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) as well as Cyclooxygenase-2 (COX-2) activity were also increased. Besides the level of pro-apoptotic markers i.e., Bax, Caspase-3 and Caspase-9 were raised, while the level of anti-apoptotic protein, Bcl-2 was reduced following the DOX intoxication. In DOX-treated rats, Histopathological observation indicated substantial hepatic tissue damage. However co-treatment with chrysoeriol remarkably reversed all the aforementioned hepatic damages. CSR demonstrated promising hepatoprotective potential through exerting antioxidant, anti-inflammatory and anti-apoptotic properties.