“Protective effects of Vincamine against Methotrexate- induced renal injury in rats”

Abstract

Abstract

Methotrexate (MTX) is a cytotoxic chemotherapeutic agent widely used in the treatment of cancer and autoimmune diseases like rheumatoid arthritis. However, its use has been limited by its nephrotoxicity. MTX-induced renal injury results in uremia which may influence both the peripheral and central nervous systems causing cognitive and memory problems. The nephroprotective and neuroprotective activities of vincamine (10, 20 & 40 mg/kg), a natural alkaloid with known antioxidant, anti-apoptotic and neuroprotective properties, were investigated against MTX-induced toxicity in rats. MTX treatment increased the markers of kidney injury and relative kidney weight, lipid peroxidation, nuclear factor-κB (NF-κB), inflammatory markers, tumor necrosis factor-α, interleukin-1β, myeloperoxidase and cyclooxygenase-2 and caspase-3 expressions, decreased catalase and superoxide dismutase activities, interleukin-10 and ATP levels and antioxidant proteins, nuclear factor erythroid 2–related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Moreover, it altered rats‘ behavior in the locomotor activity test, Y-maze and passive avoidance task. Treatment with vincamine (40 mg/kg) effectively ameliorated MTX-induced renal injury via increasing the expression of Nrf2 and HO-1 suppressing oxidative stress, decreasing the expression of inflammatory markers, NF-κB and caspase-3 pathways and enhancing ATP levels. Additionally, it restored locomotor activity in the locomotor test and the memory functions in passive avoidance and Y-maze tests. Conclusion: This study indicates that vincamine has a nephroprotective effect against MTX-induced nephrotoxicity with possible mechanisms of anti- inflammatory, anti-apoptotic and attenuating oxidative stress through up-regulating the Nrf2/HO-1 signaling pathway as well as attenuating the possible neurotoxicity effects induced by MTX