Comparative study between effect of niclosamide and vitamin c on methotrexate-induced liver injury in mice

Abstract

Background: Niclosamide is an old drug used before in the treatment of tapeworms, its main mechanism of action is through the amelioration of mitochondrial-free radical generation. It has been thought that free radical generation has an important role in methotrexate-induced liver injury. Vitamin C, an antioxidant agent, has an essential role in the methotrexate-induced oxidative stress (OS) pathways in mice hepatocytes. Aim: The aim of the study was to evaluate the effect of pretreatment with Vitamin C in different doses and niclosamide in different doses on liver injury, when we induced liver injury with methotrexate. Materials and Methods: Forty-two albino mice were divided equally into six groups, the first group was considered as “the control group,” which received a normal saline solution, the second group was considered as “Methotrexate group,” third and fourth groups were orally pretreated with “niclosamide at a dose (70 mg/kg/day) and (140 mg/kg/day)” respectively, fifth and sixth groups were orally pretreated with “Vitamin C at a dose (100 mg/kg/day) and (200 mg/kg/day),” respectively, all groups, except the control group, were injected with “Methotrexate (20 mg/kg)” intraperitoneally on the 10th day, to induced hepatotoxicity and assessed the effect of the pretreatment with these medications on OS biomarker and histopathological alteration that induced by methotrexate-induced hepatotoxicity. Results: It was found that pretreatment with niclosamide 70 mg/kg/day and 140 mg/kg/day and Vitamin C 100 mg/kg/day and 200 mg/kg/day, in mice injected with methotrexate, led to a decrease in “liver function tests, OS parameters, as well as improvement in liver tissue.” There was an improvement in “serum alanine aminotransferase, alkaline phosphatase, malondialdehyde” in addition to an improvement in “histological appearance,” but it was noted that pretreatment with niclosamide gives a better improvement in “liver function, OS, and liver tissue.” Conclusion: Niclosamide is better than Vitamin C in protecting the hepatocytes against methotrexate-induced liver injury, also niclosamide and Vitamin C have a dose-dependent protecting effect against methotrexate-induced liver injury.