Mercuric Chloride Aggravates Hyperglycemia-Induced Anxiety and Depressive-Like Behaviors in Type 2 Diabetic Rats: Breakdown of the Antioxidant Defense System.

Introduction Type 2 diabetes mellitus (T2DM) is a global health problem frequently associated with biochemical disturbance and also, with a range of mental health disorders including such as anxiety and depression. Whereas, mercury chloride (HgCl₂) is a common environmental pollutant, which is neurotoxic and induces oxidative stress, especially in metabolic disorders like diabetes. The purpose of this investigation is to evaluate the interaction between hyperglycemia-induced oxidative stress and HgCl₂ toxicity and to assess their far-reaching effect spotlighted on biochemical and behavioral disturbances. By analyzing key oxidative stress markers and anxiety- and depression-like behaviors. Experimental design was carried out as follow: control group, HgCl₂-treated group, diabetic group and diabetic HgCl₂-treated group. Type 2 diabetes was induced in a diabetic model via streptozotocin (STZ) and nicotinamide (NA) injections. For the HgCl₂-exposed groups, rats were administered 0.375 mg/kg/day of HgCl₂ orally for 45 consecutive days. Additionally, behavioral tests were performed to examine anxiety- and depression-like behaviors, and hematological, biochemical, oxidative stress markers were assessed to evaluate systemic and neurotoxic effects. The results showed significant increases in fasting blood glucose levels in diabetic and HgCl₂-treated diabetic groups compared to controls (p < 0.001). Body weight significantly decreased in all treated groups (p < 0.05), with the greatest reduction observed in the HgCl₂-treated diabetic group. Behavioral analysis revealed heightened anxiety and depression-like behaviors, particularly in the HgCl₂-treated diabetic group (p < 0.05). Biochemical assessments indicated significant disruptions in lipid profiles and hepatic and renal markers, with pronounced effects in HgCl₂-treated diabetic rats (p < 0.05). Oxidative stress markers demonstrated elevated malondialdehyde and nitric oxide levels in the liver, hippocampus, and prefrontal cortex, paired with diminished antioxidant defences, including catalase and superoxide dismutase activities (p < 0.05). These findings underscore the synergistic role of hyperglycemia and HgCl₂ exposure in amplifying oxidative damage and emotional disturbances, suggesting a critical interplay between metabolic and neurotoxic pathways.