Introduction: Obesity is a chronic condition that impairs hippocampal function by inducing oxidative stress, neuroinflammation, and reductions in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). Hydrogen sulfide (H₂S), a gaseous signaling molecule, exhibits antioxidant and neuroprotective properties. This study evaluated the effects of sodium hydrosulfide (NaHS), an H₂S donor, on hippocampal BDNF and IGF-1 expression and oxidative stress in rats fed a high-fat diet (HFD).
Methods: Forty-two adult male Wistar rats were randomly divided into six groups (n = 7 per group): control, control+NaHS (3 or 5 mg/kg), HFD, and HFD+NaHS (3 or 5 mg/kg). Rats received their assigned diets and daily intraperitoneal injections of NaHS or saline for 11 weeks. Hippocampal tissues were collected to assess BDNF and IGF-1 expression at mRNA (qPCR) and protein (ELISA) levels. Oxidative stress markers, including total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and total thiol groups (TTG), were also measured. Statistical analysis was performed using Kruskal–Wallis with Dunn’s post hoc test.
Results: Results: HFD feeding significantly reduced hippocampal BDNF and IGF-1 protein levels and TAC, while increasing TOS and MDA compared to controls (p < 0.05). NaHS administration, particularly at 5 mg/kg, restored BDNF and IGF-1 protein expression and improved oxidative balance by elevating TAC and reducing TOS and MDA (p < 0.05). No significant changes in TTG were observed. mRNA expression of BDNF and IGF-1 was less consistently altered, suggesting post-transcriptional regulation.
Conclusion: NaHS supplementation mitigates HFD-induced neurotrophic deficits and oxidative stress in the hippocampus. These findings support the neuroprotective role of H₂S and suggest its therapeutic potential in counteracting obesity-related cognitive decline.