Hepatoprotective effect of celecoxib against tamoxifen-induced liver injury via inhibiting ASK-1/JNK pathway in female rats

Abstract

Hepatotoxicity is a common side effect encountered with tamoxifen (TAM) administration. Due to the great value of TAM in breast cancer treatment, hepato-protection is seriously recommended. AimsThe present study investigated the hepato-protective effect of celecoxib (CX) against TAM-induced hepatotoxicity in rats. Main methodsFemale rats were injected with TAM (45 mg/kg, i.p.) for 7 days and given CX (15 mg/kg, orally) 7 days before TAM injection, then continued for the following 7 days. Key findingsAdministration of CX for 14 days conferred significant hepatoprotection against TAM-induced hepatotoxicity indexed by decreased liver/body weight ratio, boosted cytoprotection and substantial reduction in serum LDH activity besides functional hepatic improvement; marked decrease in ALT, AST and ALP with significant elevation in serum albumin. Oxidant/antioxidants hemostasis was improved upon CX treatment with profound decrease in hepatic MDA content and elevation of GSH and SOD levels. Furthermore, hepatic content of NO decreased along with significant decrease in ASK-1, JNK and Bax levels as well as TNFα and caspase3 expression. Finally, CX administration resulted in obvious diminution of TAM-induced necrotic and apoptotic alterations. SignificanceCelecoxib might be used in combination with TAM in treatment protocol of breast to prevent liver injury induced by TAM and further clinical studies might be needed to approve this notion.