TY  - JOUR
T1  - Amlodipine protects against methotrexate nephrotoxicity by modulating inflammation, oxidative stress, and apoptosis through NF-κB/PPAR-β/caspase 3 pathways
A1  - Shahid Karim
A1  - Dina Kutbi
A1  - Huda Alkreathy
A1  - Basma Alharthy
A1  - Mohammed Alsieni
A1  - Hussam Daghistani
A1  - Ohoud Hassan Shakroun
A1  - Mohammed Bazuhair
A1  - Mohammed Omar Barasheed
A1  - Ahmed Shaker Ali
JF  - Journal of Advanced Pharmacy Education and Research
JO  - J Adv Pharm Educ Res
SN  - 2249-3379
Y1  - 2024
VL  - 14
IS  - 4
DO  - 10.51847/niC6BprrEv
SP  - 7
EP  - 17
N2  - Methotrexate (MTX), a folic acid antagonist used for treating malignancies and autoimmune disorders, has limited use due to its toxicity, including bone marrow suppression and hepatic and renal damage. High doses of MTX (>500 mg/m²) are particularly harmful. Calcium channel blockers, such as amlodipine, may alleviate MTX-induced toxicity. This study investigated amlodipine’s potential to protect against MTX-induced acute kidney injury in rats. Thirty-two male Wistar rats were divided into four groups: a control group receiving saline, a group treated with MTX alone, and two groups receiving MTX followed by oral amlodipine at doses of 5 mg/kg or 10 mg/kg. Serum levels of kidney function biomarkers (urea, creatinine, uric acid, albumin, KIM-1, NGAL), inflammatory markers (ICAM-1, VCAM-1, IL-6, TNF-α), and oxidative stress markers (SOD, GSH, TBARS) were measured. Histopathological and immunohistochemical analyses were also performed. MTX increased serum levels of kidney function biomarkers and decreased glomerular filtration rate (GFR), which were significantly improved by amlodipine treatment. Amlodipine also reversed increases in inflammatory markers and the expression of NFκB and Caspase-3, while normalizing PPARβ levels. Histopathological findings supported these results. Thus, amlodipine demonstrates nephroprotective effects and may be a viable intervention for MTX-induced acute kidney injury‎.
UR  - https://japer.in/article/amlodipine-protects-against-methotrexate-nephrotoxicity-by-modulating-inflammation-oxidative-stress-yemfdnkig10hqgx
ER  -