Sodium cyclamate alters cardiac homeostasis via immunoinflammatory signaling modulation: A multi-biomarkers and in-silico evaluation.

Sodium cyclamate (SC) is a non-nutritive artificial food sweetener that is widely used in the food industry owing to its low cost, and long-lasting sweetness. The present investigation was planned to investigate the sub-chronic effects of SC on cardiac tissues at different dose concentrations. Thirty-six Sprague Dawley male rats were categorized into control, SC (50 mg/kg), SC (100 mg/kg) and SC (500 mg/kg) treated group. SC intoxication upregulated the expression of myeloid differentiation primary response protein (MyD88), interleukin-6 (IL-6) receptor associated kinase 1 (IRAK1), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor receptor-associated factor 6 (TRAF6), Toll-like receptor 4 (TLR4), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), while suppressing the expression of nuclear factor-kappa B inhibitor alpha (IκBα). Enzymatic activities of heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione reductase (GSR), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD) were reduced while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were escalated after SC exposure. The levels of cardiac injury markers including creatine phosphokinase (CPK), pro B-type natriuretic peptide (ProBNP), troponin-T, creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH), C-reactive protein, B-type natriuretic peptide (BNP), and troponin-I were escalated after SC administration. SC intoxication increased the levels of cysteine-aspartic protease-9 (Caspase-9), Bcl-2-associated X protein (Bax) and cysteine-aspartic protease-3 (Caspase-3) while diminishing the levels of B-cell lymphoma-2 (Bcl-2). SC administration substantially compromised the normal histology of cardiac tissues. These findings suggest that SC showed cardiotoxic effects therefore, it is imperative to conduct clinical trials to validate these findings in humans.