Alpha-Pinene Attenuates Methotrexate-Induced Kidney Damage

ÖZTÜRK et al.: Methotrexate nephrotoxicity and alpha-pinene

Abstract

This investigation assessed the potential of alpha-pinene, a natural compound that can counteract inflammation, oxidative stress, cell death and tumorigenesis, could prevent methotrexate-induced renal injury, a clinically significant complication of this frequently used chemotherapeutic agent. Sprague-Dawley rats were divided into five groups: control (CTR, no treatment), vehicle (VEH; dimethyl sulfoxide (DMSO) injected for fourteen days), alpha-pinene (AP, 50 mg/kg, daily for fourteen days), methotrexate (MTX, 20 mg/kg on 12th day of DMSO administration), and combined alpha-pinene and methotrexate treatment (APM). In the MTX group, considerable increases in blood urea nitrogen (BUN), serum creatinine, cystatin C, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1), as well as tissue levels of malondialdehyde (MDA) and Kim-1, were observed, along with a marked decrease in glomerular filtration rate (GFR). In the APM group, BUN, creatinine, cystatin C, NGAL, and GFR values showed partial improvement, while the reductions in Kim-1 and MDA levels were more pronounced. Histopathological inspection demonstrated that alpha-pinene pretreatment considerably minimized methotrexate-induced tubular and glomerular deterioration. Our findings indicate that, although alpha-pinene does not completely prevent methotrexate-induced renal injury, it shows strong potential as a protective and supportive therapeutic agent against nephrotoxicity. More research is needed to reveal its molecular mechanisms of action and determine the optimal dosage for maximizing its renoprotective efficacy.