The College of Pharmacy discussed the Ph.D. thesis tagged (Effects of Pyridoxine and Cyanocobalamin each alone and in Combination on Methotrexate-induced Nephrotoxicity in Rats) for the student Noor Mohammed Mohammed Zakri in the Pharmacology and Toxicology Department. This thesis was designed to evaluate the effects of two doses of each of pyridoxine and cyanocobalamin intraperitoneally injected alone, and both in combination on methotrexate-induced nephrotoxicity in rats. Eighty rats were randomly divided into eight groups (10 rats in each group) as follows: Group- I: For 7 days, rats were injected with normal saline. Group- II: Rats injected with a single dose (20mg/kg of methotrexate) on day 2. Groups III and IV received pyridoxine injections (33mg/kg/day and 100mg/kg/day) once daily for 7 days, with methotrexate injections on day 2.Groups V and VI: Rats were given cyanocobalamin injections (0.5mg/kg/day and 2mg/kg/day) once daily for seven days, with methotrexate injections on day two. Group VII: Rats injected the combination of 33mg/kg/day pyridoxine and 0.5mg/kg/day cyanocobalamin for 7 days, and methotrexate injection at day 2. Group VIII: Rats were given 100mg/kg/day pyridoxine and 2mg/kg/day cyanocobalamin for 7 days, followed by a methotrexate injection on day 2. The normal saline, methotrexate, and the 2 doses of each of pyridoxine and cyanocobalamin were intraperitoneally-injected. Twenty-four (24) hours after the end of the treatment duration, rats in each group were euthanized by diethyl ether, and serum was utilized for the estimation of neutrophil gelatinase-associated lipocalin and creatinine levels. Kidney tissue homogenate was utilized for the estimation of reduced glutathione level, MDA content, and SOD activity, gene expression of renal KEAP-1, Nrf2, and HO-1 by quantitative reverse transcription polymerase chain reaction and histological study. The thesis concluded that pyridoxine at a dose (33mg/kg/day) [on some parameters], and (100mg/kg/day), cyanocobalamin (0.5mg/kg and 2mg/kg/day, each), and their combination have nephroprotective effects against methotrexate in rats, as evident by -lowering serum levels of neutrophil gelatinase-associated lipocalin and creatinine, -ameliorating oxidative markers, and regulating the “keap-1/Nrf-2/HO-1” signaling pathway; furthermore, there were improvements in histopathological lesions in all treated rats’ Groups (III-VII), and the histological structural appearance of renal epithelial tubules were looked-like normal in Group VIII rats (100mg/kg/day pyridoxine and cyanocobalamin 2mg/kg/day with MTX), thus better protection is achieved against MTX nephrotoxicity.
