Background: D-galactose (D-gal) is commonly used to induce aging-related changes, including oxidative stress and impaired redox homeostasis. Indole-3-propionic acid (IPA) is a gut microbiota-derived tryptophan metabolite with antioxidant properties. However, its effects on hippocampal oxidative and redox changes following D-gal exposure are not fully understood. This study evaluated the effect of IPA on oxidative markers, antioxidant defense, and glutathione status in the hippocampus of D-gal-treated rats.
Methods: Forty male Wistar rats were divided into five groups (n=8): Control, D-gal, Control+IPA, D-gal+IPA10, and D-gal+IPA20. D-gal (500 mg/kg/day) was administered intraperitoneally for 8 weeks, followed by oral administration of IPA for 8 weeks. Levels of advanced glycation end products (AGEs), malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), GSSG/GSH ratio, and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured in the hippocampus.
Findings: D-gal exposure increased AGEs, MDA, GSSG levels, and the GSSG/GSH ratio, while decreasing GSH levels and the activity of SOD, CAT, and GPx. IPA treatment at both doses decreased AGEs, MDA, and GSSG, while increasing GSH, SOD, and GPx. CAT activity increased only with the IPA20 dose. The GSSG/GSH ratio showed a significant decrease in the IPA-treated groups.
Conclusion: Chronic D-gal administration was associated with increased oxidative damage and impaired glutathione homeostasis. IPA reduced lipid peroxidation and improved antioxidant enzyme activity, suggesting it may play a role in modulating oxidative and redox disturbances associated with D-gal-induced aging.