Comparative Biochemical Profiling of Aluminum Chloride and Sodium Azide Induced Neuroinflammation and Cardiometabolic Disturbance

[Image: see text] Comorbidities in human beings signify the numerous risk factors that increase the incidences of neuro- and cardio-metabolic disorders. Experimental models depicting comorbidities are important to explore the molecular pathophysiology that can help suggest appropriate treatment strategies. Tissue-accumulating potential and pathological effects of aluminium chloride (AlCl(3))and sodium azide (NaN(3)) are well recognized. Hence, in the current work, we have for the first time aimed to investigate the unexplored potential of graded dose effects of AlCl(3) and NaN(3) in inducing early inflammation and cardiometabolic toxicity via comparative biochemical analysis of AlCl(3) and/or NaN(3). Rats were allocated into seven groups (n = 6). Group 1 was normal control. Remaining groups were given graded doses of AlCl(3) and/or NaN(3), as LD-AlCl(3) (AlCl(3) 40 mg), MD-AlCl(3) (AlCl(3) 45 mg), and HD-AlCl(3) (AlCl(3) 50 mg) representing low dose, medium dose, and high dose of AlCl(3), respectively, and the remaining as LD-NaN(3) (NaN(3) 13 mg), MD-NaN(3) (NaN(3) 15 mg), and HD-NaN(3) (NaN(3) 17 mg) representing low dose, medium dose, and high dose of NaN(3), respectively. Serum levels of glucose, insulin, lipid profile, inflammatory mediators like IL-6 and oxidative stress marker, and malondialdehyde (MDA) were analyzed. Likewise, subacute toxicity parameters were analyzed. Immunohistochemistry (IHC) and histopathology (H&E/Masson’s trichrome staining) of brain, heart, and pancreatic tissues were done. ECG pattern of all groups was observed. HD-AlCl(3) was associated with elevated levels of inflammatory biomarkers, MDA, and glycemic and lipid profiles, whereas it decreased the insulin levels. HD-NaN(3) also showed the similar effects of aggravated inflammatory biomarkers, impaired glycemic and lipid profiles, but depicted the maximum mortality rate as compared to HD-AlCl(3). IHC showed prominent amyloid plaques and neurofibrillary tangle formation with MD-AlCl(3) and HD-AlCl(3) as compared to NaN(3)-treated groups. Likewise, in brain tissues, vacuolation of white matter, vascular congestion, and hemorrhage were seen in HD-AlCl(3) treated group, while HD-NaN(3) induced death in animals. AlCl(3) exposure resulted in an inverted QRS complex, while exposure to NaN(3) showed ST depression but with increased mortality. AlCl(3) has better controlled results as compared to NaN(3) for induction of comorbid experimental animal model depicting early neuroinflammation and cardiometabolic disruption. These determined efforts facilitate the researchers for the development of clinically effective treatment strategies using such experimental models.