A high-fat diet (HFD) induces oxidative stress and reduces hippocampal neurotrophic factors, contributing to cognitive impairment. Hydrogen sulfide (H₂S) is an endogenous gaseous signaling molecule wi Show more
A high-fat diet (HFD) induces oxidative stress and reduces hippocampal neurotrophic factors, contributing to cognitive impairment. Hydrogen sulfide (H₂S) is an endogenous gaseous signaling molecule with recognized neuroprotective and antioxidant properties. This study investigated the effects of sodium hydrosulfide (NaHS), an H₂S donor, on hippocampal brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and oxidative stress in rats fed an HFD. Forty-two adult male Wistar rats were assigned to control or HFD groups, with or without daily NaHS administration (3 or 5 mg/kg) for 11 weeks. HFD feeding significantly decreased hippocampal BDNF and IGF-1 protein levels and reduced the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSR). NaHS treatment, particularly at 5 mg/kg, restored neurotrophic protein levels and normalized antioxidant enzyme activities. These effects occurred without consistent changes in mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings demonstrate that H₂S mitigates HFD-induced neurotrophic and oxidative deficits, supporting its potential as a therapeutic strategy for obesity-related hippocampal dysfunction. Show less