Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic aqueous extract in rat

Abstract

Background/aim: Methotrexate (MTX) has been widely used for treatment of cancer and rheumatoid arthritis, but its use has been limited by its nephrotoxicity. This study was carried out to determine whether garlic exerts a protective effect against MTX-induced nephrotoxicity.

Materials and methods: Nephrotoxicity was induced in rats after a single i.p. injection of MTX (20 mg/kg). Garlic extract (1 mL/100 g b.w.) was given orally for 7 days before and after MTX administration. Serum samples were collected to evaluate urea, creatinine, sodium, phosphorous, potassium, and calcium. Reduced glutathione, catalase, adenosine deaminase, nitric oxide, and malondialdehyde were measured in renal tissue. Tubular injury was evaluated by histopathological examination.

Results: MTX increased urea and creatinine levels and led to imbalances in some electrolytes. It also depleted renal antioxidant enzyme levels and increased malondialdehyde, adenosine deaminase, and nitric oxide levels. Histopathological examination showed glomerular and tubular alterations. Pretreatment with garlic significantly improved renal function and increased renal antioxidant enzyme activities. Furthermore, garlic reduced renal oxidative stress and prevented alterations in renal morphology.

Conclusion: Garlic treatment has a reversible biochemical and histological effect upon MTX-induced nephrotoxicity.