Abstract

This study aims to investigate the effect of aspirin in methotrexate toxicity (increase or decrease) relating to oxidative stress and histopathological changes of the liver and kidney in male rats. Twenty rats were divided into equal 4 groups, the first is considered control group, the second was treated with methotrexate in a dose of 10 mg/kg, the third was treated with methotrexate and aspirin in doses of 10 and 30 mg/kg respectively, the fourth was treated with aspirin alone with a dose of 30 mg/kg. All doses were given by daily oral dosage for 4 constitutive days. The result revealed a significant decrease in the concentration of both glutathione and albumin and a significant increase in the concentration of both malondialdehyde and ALT enzyme in the two groups treated with methotrexate alone or in combination with aspirin as compared to the control group. The histopathology revealed that the severity of lesions was in the group of methotrexate with aspirin, group of methotrexate only and a group of aspirin respectively, which are representing by coagulative necrosis and hypertrophy of hepatocytes in the liver while the lesions of kidney were atrophy of some glomeruli and renal cystic formation. The study concludes that aspirin increases the toxic effect of methotrexate at the level of oxidative stress concomitant with the occurrence of hepatic and renal toxicity.

Highlights

  • Methotrexate is used in the treatment of cancer and psoriatic rheumatoid arthritis Methotrexatebegan and extended to be used for chemotherapy [1]

  • This study aims to investigate the effect of aspirin in methotrexate toxicity relating to oxidative stress and histopathological changes of the liver and kidney in male rats

  • The present study aims to investigate the effect of aspirin in methotrexate toxicity relating with oxidative stress and histopathological changes in liver and kidney in male rats

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Summary

Introduction

Methotrexate is used in the treatment of cancer and psoriatic rheumatoid arthritis Methotrexatebegan and extended to be used for chemotherapy [1]. It is efficient for the therapy of breast, lung and bladder cancer, as well as other blood cell cancer [2]. Mechanism of action of Methotrexate is competitive inhibition of dihydrofolate reductase enzyme (DHFR) cause inhibiting of folic acid, some proteins and nucleic acid synthesis [3]. Methotrexate has a toxic effect on the liver, kidney and other organs. The most common adverse effects of methotrexate to the kidney because of its excretion and it metabolite in the liver leading to hepatotoxicity

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