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

Abstract

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 (AlCl3)and sodium azide (NaN3) 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 AlCl3and NaN3in inducing early inflammation and cardiometabolic toxicity via comparative biochemical analysis of AlCl3and/or NaN3. Rats were allocated into seven groups (n = 6). Group 1 was normal control. Remaining groups were given graded doses of AlCl3and/or NaN3, as LD-AlCl3(AlCl340 mg), MD-AlCl3(AlCl345 mg), and HD-AlCl3(AlCl350 mg) representing low dose, medium dose, and high dose of AlCl3, respectively, and the remaining as LD-NaN3(NaN313 mg), MD-NaN3(NaN315 mg), and HD-NaN3(NaN317 mg) representing low dose, medium dose, and high dose of NaN3, 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-AlCl3was associated with elevated levels of inflammatory biomarkers, MDA, and glycemic and lipid profiles, whereas it decreased the insulin levels. HD-NaN3also showed the similar effects of aggravated inflammatory biomarkers, impaired glycemic and lipid profiles, but depicted the maximum mortality rate as compared to HD-AlCl3. IHC showed prominent amyloid plaques and neurofibrillary tangle formation with MD-AlCl3and HD-AlCl3as compared to NaN3-treated groups. Likewise, in brain tissues, vacuolation of white matter, vascular congestion, and hemorrhage were seen in HD-AlCl3treated group, while HD-NaN3induced death in animals. AlCl3exposure resulted in an inverted QRS complex, while exposure to NaN3showed ST depression but with increased mortality. AlCl3has better controlled results as compared to NaN3for 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.