Repeated Humanin Treatment Attenuates Oxidative Stress, Inflammation, and Apoptosis in Diabetic Cardiac Tissue

Abstract

Diabetes mellitus (DM) markedly increases the risk of cardiovascular complications through mechanisms involving hyperglycemia-induced oxidative stress, inflammation, and apoptosis. Humanin (HN), a mitochondria-derived peptide with established cytoprotective properties, has been reported to exert antioxidant and anti-apoptotic effects in several experimental models. However, its role in diabetic cardiac injury remains insufficiently understood. The present study investigated the protective effects of repeated HN treatment against diabetes-induced cardiac injury in a streptozotocin (STZ)-induced mouse model. Mice were divided into four groups: control, HN-treated, STZ-induced diabetic, and STZ + HN-treated groups (n = 10/group). HN (4 mg/kg) was administered daily for 15 consecutive days. Biochemical analyses were performed to evaluate oxidative stress, inflammatory cytokines, and apoptotic markers. STZ-induced diabetes significantly increased oxidative stress markers, pro-inflammatory cytokines, and apoptotic activity while reducing antioxidant defenses and anti-inflammatory cytokines compared with controls. Repeated HN treatment markedly attenuated these alterations and restored redox and inflammatory balance in diabetic cardiac tissue. These findings demonstrate that repeated HN treatment attenuates oxidative stress, inflammation, and apoptosis in the hearts of diabetic mice. The results further suggest that HN may represent a promising therapeutic candidate for limiting diabetes-associated cardiac complications.