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 AlCl3 and NaN3 in inducing
early inflammation and cardiometabolic toxicity via comparative biochemical analysis of AlCl3 and/or NaN3. Rats were allocated into seven groups (n = 6). Group 1 was normal control. Remaining groups were given graded
doses of AlCl3 and/or NaN3, as LD-AlCl3 (AlCl3 40 mg), MD-AlCl3 (AlCl3 45
mg), and HD-AlCl3 (AlCl3 50 mg) representing
low dose, medium dose, and high dose of AlCl3, respectively,
and the remaining as LD-NaN3 (NaN3 13 mg), MD-NaN3 (NaN3 15 mg), and HD-NaN3 (NaN3 17 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-AlCl3 was associated with elevated levels
of inflammatory biomarkers, MDA, and glycemic and lipid profiles,
whereas it decreased the insulin levels. HD-NaN3 also 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-AlCl3 and
HD-AlCl3 as compared to NaN3-treated groups.
Likewise, in brain tissues, vacuolation of white matter, vascular
congestion, and hemorrhage were seen in HD-AlCl3 treated
group, while HD-NaN3 induced death in animals. AlCl3 exposure resulted in an inverted QRS complex, while exposure
to NaN3 showed ST depression but with increased mortality.
AlCl3 has better controlled results as compared to NaN3 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.