Alogliptin Mitigates Methotrexate-Induced Nephrotoxicity in a Rat Model: Antagonizing Oxidative Stress, Inflammation...

Although methotrexate (MTX) is a magnificent cure for cancerous neoplasms and inflammatory disorders, its usage is bound due to associated hazards, especially nephrotoxicity. The present study investigated the possible therapeutic impact of alogliptin (ALO), prescribed for managing type 2 diabetes, on renal injury caused by MTX and explored the mechanisms that could illustrate this suggested protective effect. Four rat groups were involved: control, ALO (20 mg/kg/d, intragastrically (I.G.)) for ten days, MTX, and MTX + ALO groups. The latter two groups were given MTX (20 mg/kg, I.P.) on the 7th day, while the MTX + ALO group was administered ten days of 20 mg/kg of ALO. A significant impairment in renal function, catalase activity, reduced glutathione content, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expressions, coupled with an increase in kidney injury molecule-1 (KIM-1), malondialdehyde, tumor necrosis factor-alpha (TNF-α), and cleaved caspase-3 (c-caspase-3) expressions, was observed in MTX-intoxicated rats, evidenced by remarkable deterioration in renal construction. Conversely, ALO improved renal function and architecture. Moreover, ALO retrieved the oxidative balance, the attenuated Nrf2/HO-1 expression, and the elevated KIM-1, TNF-α, and c-caspase-3 expression. In conclusion, ALO might abrogate MTX-elicited kidney damage by rectifying the deviation in oxidative status, apoptotic and inflammatory pathways, paving the way for managing MTX-induced nephrotoxicity.