The protective effect of low dose methotrexate on renal ischemia- reperfusion injury

Document Type : Original Article

Authors

1 Department of Pharmacology and Toxicology-Faculty of Pharmacy-Zagazig University- Zagazig Egypt.

2 Department of Pharmacology and Toxicology-Faculty of Pharmacy-Zagazig University- Zagazig Egypt

Abstract

Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. This study was designed to investigate the effects of low-dose methotrexate in I/R-induced renal injury in rats.
Forty male albino rats were divided equally into five groups: (I) control; (II) sham operated (only unilateral nephrectomy); (III) I/R; (IV) methotrexate (0.5 mg/kg prior to experiment) plus I/R; and (V) levamisole (12.5 mg/kg prior to experiment) plus group IV. In groups III, IV and V after unilateral nephrectomy, the rats were subjected to 45 min of left renal pedicle occlusion, followed by 6 h of reperfusion. At the end of the reperfusion period, rats were killed and kidneys and blood were removed. Myeloperoxidase and superoxide dismutase activities, and interleukin 10, malondialdehyde, monocyte chemoattractant protein 1, reduced glutathione and tumor necrosis factor alpha contents were determined in renal tissue. Serum creatinine and blood urea nitrogen were measured for the evaluation of renal function.
After I/R, increases were found in serum levels of creatinine and urea, MPO activity, tissue contents of MDA, MCP-1 and TNF-α. In contrast, SOD activity, GSH and IL-10 contents were decreased. After the administration of a low-dose of methotrexate, decreases were observed in serum levels of creatinine and urea, MPO activity, tissue contents of MDA, MCP-1 and TNF-α. In contrast, SOD activity, GSH and IL-10 contents were increased. These effects diminished in presence of levamisole. Low-dose methotrexate exhibits meaningful renoprotective activity following ischemia–reperfusion injury of the kidney.

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