Chia Seeds Oil Inhibits Hepatic Resistance to Doxorubicin Via Suppressing Cyp3-A4 and Mrp-1 in Male Albino Rats

Abstract

Background:The oil-seed of chia (Salvia hispanica L.), CSO, had been reported for many biological activities. Doxorubicin (DOX) is one of the active chemotherapies for hepatocellular carcinoma. DOX-resistance is the cause of its limited use. Objectives: This study aimed to explore the influence of CSO on DOX-induced resistance and antioxidant status. Methods: 40 male albino rats weighing 150-200g were divided equally into four groups 10/ each. CSO (5% w/w) were administrated oral daily for 30 consecutive days. DOX treated groups were injected IP at a dose of 2.5 mg/kg trice weekly to be totally 15 mg/kg for two weeks. G1 Control, G2 CSO, G3 Doxorubicin, G4 CSO/DOX. Antioxidant activity, histopathological examination, immunohistochemical analysis of CYP3A4, MRP-1, and c-MYC proteins and expression of miRNAs were assayed. Results: Findings indicated that CSO treatment led to a suppression in hepatotoxicity, nephrotoxicity and cardiotoxicity induced by DOX in male albino rats evidenced by a significant enhancement in the activity of ALT, GGT, LDH, AST, also creatinine and uric acid. CSO induced antioxidant activity GSH, CAT and inhibited MDA. Histopathological examination in sections of liver, kidney and heart tissues were confirmed these findings. In liver tissues, DOX resulted in an observable induction in CYP3A4 and MRP-1, while CSO/DOX showed an inhibition in both proteins. c-MYC was dramatically decreased in DOX group, while CSO/DOX group restored cellular c-MYC. CSO/DOX group resulted in a remarkable inhibition in the tumor suppressor miRNA (let-7a) compared to DOX-induced expression. Moreover, miR-122, as negative regulator of DOX resistance, showed a dramatic induction in CSO/DOX group compared to DOX group. Conclusion, CSO is capable of effectively inhibit DOX resistance, induced hepatic, nephro and cardiac antioxidant status, inhibit lipid peroxidation, and restore hepatic function.