Involvement of Nrf2/HO-1 antioxidant signaling and NF- κB inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: cross talk between nephrotoxicity and neurotoxicity.

Involvement of Nrf2/HO-1 antioxidant signaling and NF-κB inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: cross talk between nephrotoxicity and neurotoxicity.
Arch Toxicol. 2019 Apr 24;:
Authors: Shalaby YM, Menze ET, Azab SS, Awad AS
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 and 40 mg/kg), a natural alkaloid with known anti-oxidant, anti-apoptotic and neuroprotective properties, were investigated against MTX-induced toxicity. 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 disturbed rats' behavior in the locomotor activity test, Y-maze and passive avoidance task. ...

Source: Archives of Toxicology - April 23, 2019 Category: Toxicology Authors: Shalaby YM, Menze ET, Azab SS, Awad AS Tags: Arch Toxicol Source Type: research