Astaxanthin effect on apoptotic biomarkers in methotrexate-induced liver injury

Abstract

Methotrexate is used in the treatment of cancer, psoriasis, rheumatoid arthritis and several other disorders. It has a hepatotoxic potential side effect. Patients who have no access to alternative medications face a serious challenge as a result. The current study aimed to assess the apoptotic potential of methotrexate on liver cells and evaluate the hepatoprotective activity of the potent antioxidant astaxanthin, by downregulation of apoptotic biomarkers caspase 9 and caspase 3. A model of methotrexate-induced liver toxicity was employed on male rats. Thirty-six rats were divided into six groups; a negative control group, methotrexate induction group given (20 mg/kg) on day 13, three groups pretreated with astaxanthin in ascending doses (50, 75 and 100 mg/kg) for 14 days before methotrexate, and a conventional therapy group pretreated with silymarin (200mg/kg). The use of methotrexate significantly increased liver tissue caspase 9 and caspase 3 compared to the negative control. On the other side, astaxanthin used in all three doses significantly normalized these biomarkers. This study revealed that since astaxanthin significantly decreased caspase 9 and caspase 3 that are involved in the apoptotic pathway, it could be used as pretreatment in patients treated with methotrexate to alleviate its hepatotoxicity.

Keywords

• Methotrexate, hepatotoxicity, astaxanthin, caspase 9 and caspase 3.