Objectives:
Drug-induced liver injury is a common adverse reaction that frequently occurs with chemotherapeutic agents, such as cisplatin (CIS). The present study seeks to enhance our comprehension of drug actions and their associated adverse effects by examining the toxicity of cisplatin on rat liver tissue. Basically, we aim to investigate the potential hepatoprotective effects of irbesartan (IRB), an easily accessible angiotensin II receptor blocker, in mitigating the hepatotoxicity induced by cisplatin.
Methods:
Wistar albino rats were divided into four groups. These groups included a control group (saline, peroral [p.o.] for seven days, and 1 ml saline intraperitoneal [i.p.] on the fourth day); a CIS group (1 ml saline for seven days and 7.5 mg/kg CIS i.p. on the fourth day); a CIS+IRB group (IRB: 50 mg/kg p.o. for seven days and 7.5 mg/kg CIS i.p. on the fourth day); an IRB group (50mg/kg IRB p.o. for seven days). The effect of Irbesartan on IL-1 beta (IL-1β) and Caspase 3 levels was evaluated by immunohistochemical analysis, and its effects on mRNA expression levels of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and Immunoglobulin-heavy-chain-binding protein (BiP) were tested by quantitative real-time polymerase chain reaction (qRT-PCR).
Results:
The administration of irbesartan mitigated cisplatin-induced liver toxicity by inhibiting endoplasmic reticulum (ER) stress. Specifically, this drug reduced the mRNA expression of ER stress markers, including CHOP and BiP. In addition, irbesartan treatment decreased oxidative stress, inflammatory responses, and apoptotic markers.
Conclusion:
These findings suggest that irbesartan may be a promising therapeutic option for preventing cisplatin-induced liver injury, potentially by modulating ER stress-related pathways.
Keywords: Cisplatin, ER-stress, Irbesartan, Liver toxicity.