Haematological and Metabolic Disturbances Induced by Chronic Unpredictable Stress in Albino Wistar Rats

Introduction: Chronic stress serves as a fundamental factor contributing to various health conditions, including atherosclerosis, hypertension, and cardiac dysfunction. Previous findings from our laboratory have revealed a clear link between chronic stress and increased occurrence of heart dysfunction, atherosclerosis, immune imbalance and psoriasis. Methods: However, the haematological and metabolic pathways involved remain unexplored. Therefore, our investigation focused on examining the haematological and metabolic profiles of rats subjected to chronic stress. Animals were divided into two groups: Group-I (Control) was left undisturbed for 56 days. Group-II (CUS) was exposed to a random stressor for 56 days, following which stress induction was verified by a significant increase in serum corticosterone level (p<0.0001) and depressive-like behaviours using novelty-suppressed feeding test (NSFT) (p<0.0001). Blood profile analysis of CUS animals demonstrated anaemia with decreased RBC (p=0.0001) and elevated WBC count (p<0.0001). Results: Serum electrolyte analysis of CUS rats revealed hypercalcemia, hyponatremia, and hypokalaemia. Serum lipid profile analysis showed increased triglyceride (p=0.007) and VLDL (p=0.007) levels. Serum proinflammatory cytokine levels were also increased in CUS rats. Moreover, metabolomics analysis of CUS animals revealed decreased concentrations of myo-inositol, threonine, glycine, glutamine, methionine, and formate, along with an increased fumarate-to-alanine and fumarate-to-glycine ratio. These metabolic alterations suggest reduced glycolysis and abnormal amino acid metabolism and are associated with inflammation, cell damage, endothelial dysfunction, hypertension, metabolic disorders, and diabetes, among other conditions. Conclusion: These findings reveal haematological and metabolic alterations in response to stress and may provide critical insights to lay the foundation for developing targeted therapeutic interventions to prevent stress-related diseases.