Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity

Abstract

Methotrexate (MTX) is a generally applied chemotherapeutic medicine in most cancers treatment. Morin hydrate, a robust antioxidant, is a secondary metabolite observed in numerous plants, along with figs, white mulberries, and others. The hypothesis of this study is that morin hydrate can effectively reduce MTX-induced kidney injury in rats by increasing antioxidant enzyme activity and inhibiting apoptotic processes. This study, 35 male Wistar albino rats were used, and five different experimental groups, each consisting of 7 rats were established. Group 1 served as the control group while Group 2 received morin exclusively via oral administration (at a dose of 100 mg/kg). Group 3, however, was administered MTX exclusively (at a dose of 20 mg/kg). Group 4 received a combination of MTX (20 mg/kg) and morin (50 mg/kg), and Group 5 received a combination of MTX (20 mg/kg) and morin (100 mg/kg). The MTX group showed a significant increase in kidney biomarkers, including serum urea, creatinine, and the lipid peroxidation biomarker MDA, compared to the control group, along with a notable decrease in antioxidant enzyme activity (SOD, CAT, GPx) and GSH levels. Furthermore, MTX notably decreased the expression of procas-3, Bcl-2, procas-9, and procas-8 while concurrently increasing the expression of apoptotic genes such as CYT-C and Bax. Co-administration of morin hydrate with MTX at doses of 50 and 100 mg/kg effectively managed oxidative damage levels and apoptotic markers, demonstrating antioxidant and anti-apoptotic properties. Notably, the 100 mg/kg dose provided more robust protection than the 50 mg/kg dose, indicating a dose-dependent efficacy. This investigation thus supports the conclusion that morin hydrate, at both dosage levels, effectively mitigates MTX-induced renal damage.