Protective role of carvacrol and carnosine against cadmium-induced liver injury via reducing oxidative stress, inflammation, and apoptosis

Abstract

This study investigated the protective effects of carnosine and carvacrol against cadmium-induced hepatotoxicity and elucidated the associated cellular mechanisms in a rat model. Rats were allocated into five equal groups: control, Cd, Cd + CAR10, Cd + CRV50, and Cd + CAR10 + CRV50. While the control group remained untreated, the remaining four groups received intraperitoneal (IP) cadmium (2 mg/kg) three times weekly for a duration of four weeks, after that the 3rd, 4th, and 5th groups were treated with carnosine, carvacrol, or a combination of them (10 and 50 mg/kg, IP) once daily for 2 consecutive weeks. At the end, hepatic function was evaluated by measuring serum ALT, AST, and ALP levels, as well as the lipid profile, to determine the hepatoprotective efficacy of carnosine and carvacrol. Both agents significantly improved liver biochemical parameters and attenuated histopathological alterations. Moreover, they alleviated cadmium (Cd)-induced hepatic oxidative stress and endoplasmic reticulum (ER) stress, as evidenced by the upregulation of key antioxidant defenses and the downregulation of ER stress–associated markers. Carnosine and carvacrol suppressed the expression of pro-inflammatory cytokines while enhancing the expression of the anti-inflammatory cytokine IL-10, thereby contributing to the restoration of hepatic homeostasis. Carnosine and carvacrol induced apoptotic cascades by deregulating the pro-apoptotic Bax marker, concomitant with increased anti-apoptotic Bcl-2 mRNA expression. Furthermore, histopathological examination indicated severe hepatic tissue damage in Cd-treated rats, which was improved in the treated groups. This study demonstrated that carnosine and carvacrol exhibit significant antiapoptotic effects and hepatoprotective effects against Cd-induced hepatic toxicity.