L-Carnitine Attenuates Testicular Dysfunction in Type 1 Diabetes Mellitus Via Modulation of Oxidative Stress, Inflammation, and miRNA Expression

Type 1 diabetes mellitus (T1DM) is a significant global health concern, adversely affecting various metabolic pathways and organ systems, including male reproductive health. This study aimed to investigate the protective effects of L-carnitine on T1DM-induced testicular dysfunction through its antioxidant and anti-inflammatory mechanisms. Male rats were divided into control, T1DM, L-carnitine, and T1DM + L-carnitine groups. After 8 weeks of treatment, serum glucose, blood HbA1c, testicular oxidative stress markers (TAC, TOS, MDA, and protein peroxidation), Pro-Inflammatory cytokines (IL-1β, IL-6, and TNF-α) and testosterone levels were measured. Additionally, the histological changes, sperm count, and miRNA expression (miR-155, miR-155-5p, and miR-132) were also studied. Results showed that T1DM significantly elevated oxidative stress markers, pro-inflammatory cytokines, and miRNA expression while reducing TAC, testosterone, sperm count, and Johnson’s score. Severe histological alterations, including germinal cell dissociation and atrophied seminiferous tubules, were observed in T1DM rats. L-carnitine treatment reduced oxidative stress and pro-inflammatory cytokines level, decreased lipid and protein peroxidation (> 3-fold), downregulated the miR-155, miR-155-5p, and miR-132 expression in diabetic rats (> 3-fold). Moreover, TAC (> 3-fold), testosterone levels (1-fold), sperm count, and testicular histological changes were restored by L-carnitine in diabetic rats. These findings suggest that L-carnitine ameliorates T1DM-induced testicular dysfunction through its dual antioxidant and anti-inflammatory properties. In line, L-carnitine significantly restored antioxidant capacity by directly scavenging reactive oxygen species, thereby reducing oxidative damage to lipids and proteins. These findings suggest that L-carnitine ameliorates T1DM-induced testicular dysfunction by enhancing antioxidant capacity and downregulating pro-inflammatory miRNAs (miR-155, miR-155-5p, miR-132).