Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat.
Biochem Pharmacol. 2020 Jun 6 ;178:114083. Epub 2020 Jun 6. PMID: 32522593
Jariya Umka Welbat
Methotrexate (MTX) induces the formation of reactive oxygen species (ROS) and leads to neurotoxicity. The drug also negatively impacts neurogenesis and memory. Hesperidin (Hsd) is a major flavanoid with multiple beneficial pharmacological effects such as anti-oxidation, anti-inflammation, and neuroprotective effects. The aim of our study was to investigate the neuroprotective effects of Hsd against MTX-induced alterations in oxidative stress and neurogenesis. Sprague Dawley rats were divided into four groups: 1) a vehicle group, which received saline and propylene glycol, 2) an Hsd group, which was orally administered with Hsd (100 mg/kg) for 21 days, 3) an MTX group, which received MTX (75 mg/kg) by intravenous injection on days 8 and 15, and 4) an MTX + Hsd group, which received both MTX and Hsd. After treatment with MTX, p21-positive cells had increased significantly and doublecortin (DCX) expression in the hippocampus had decreased significantly. Treatment with MTX also increased malondialdehyde (MDA) in both the hippocampus and prefrontal cortex and decreased levels of brain-derived neurotropic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and prefrontal cortex. Additionally, there were significant decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus and prefrontal cortex in the MTX group. However, co-treatment with Hsd ameliorated the negative effects of MTX on neurogenesis, oxidative stress, and antioxidant enzymes. These findings suggest that Hsd may be able to prevent neurotoxic effects of MTX by reducing oxidative stress and enhancing hippocampal neurogenesis.