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TITLE:

PROTECTIVE EFFECT OF N-ACETYL CYSTINE AGAINST METHOTREXATE INDUCED HEPATOTOXICITY IN MICE

AUTHORS:

Dr Muhammad Adnan Sadiq, Dr Ahsan Shahzad, Dr. Haroon Ashraf

ABSTRACT:

Background and objective: The liver is the largest internal organ by percent weight in the human body and has crucial functions. N-acetylcysteine (NAC) is a well-established cytoprotective drug that has proven efficacy against drug (acetaminophen overdose)-induced hepatotoxicity. Therefore, the basic aim of this study is to analyses the protective effect of N-Acetyl Cystine against Methotrexate induced hepatotoxicity in mice. Material and methods: This experimental study was conducted in Shahida Islam medical and dental college Lodhran during March 2019 to December 2019. In this study we used the 55 male albino mice. The 55 rats were randomly assigned to one of five groups, with an equal number of rats contained within each group. Forty-four rats were administered a single dose of 20 mg/kg methotrexate without or with daily treatments of 50 mg/kg oral NAC (MTX + NAC group), 50 mg/kg per day (single dose). The dose and duration of MTX and antioxidant agents were selected according to results from previous studies. Results: This experimental study consist of 55 male albino mice. As compared to the control group, the experimental group showed significantly higher levels of serum ALT (P = 0.001) and significantly lower levels of AST (P = 0.001). None of the antioxidant treatments affected the MTX-induced ALT levels (all, P > 0.05), but the NAC treatment produced a significant decrease in the MTX-induced serum AST level (P < 0.05). MTX exposure appeared to have no effect on either ALP or TBil levels in serum (P > 0.05 vs control group). Conclusion: It is concluded that the mechanism of MTX-induced hepatic injury likely involves oxidative stress pathways; development or progression of this life-threatening condition may be prevented by prophylactic or therapeutic delivery of antioxidant agents, such as NAC.

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