Potassium sorbate instigates sub-chronic cardiotoxicity via dysregulating TLR4/MyD88 and NF-κB pathway: A biochemical, radiological, histological, and computational validation.

Potassium sorbate (PS) is a popular food preservative that is widely used to increase the shelf life of several food items such as dairy products, bakery products, and drinking beverages. However, its long-term cardiovascular safety remains inadequately explored. The current study was aimed at exploring the sub-chronic cardiotoxic effects of PS using different doses in rat's model. Thirty-six male Sprague Dawley rats were randomly divided into four groups: control, PS (25 mg/kg), PS (50 mg/kg), and PS (100 mg/kg). Sub-chronic PS exposure led to a significant upregulation of inflammatory and immune-related genes, specifically the toll-like receptor 4 (TLR4), nuclear factor kappa B, COX-2, IL-6, myeloid differentiation primary response 88, IL-1β, tumor necrosis factor receptor-associated factor 6 (TRAF), TIR-domain-containing adapter-inducing interferon (TRIF), tumor necrosis factor alpha (TNF-α) and interleukin-18 (IL-18). PS intoxication resulted in severe cardiac impairments which is characterized by alterations of redox homeostasis, excessive oxidative stress, and activation of inflammatory signaling pathways. These alterations were accompanied by induction of pro-apoptotic pathway as confirmed by elevated levels of caspase-3, caspase-9, and Bax, while a significant reduction in the levels of Bcl-2. Moreover, PS exposure resulted in structural and functional cardiac impairments, as confirmed by echocardiographic and elevated levels of cardiac function markers. Histopathological analysis showed that PS administration induces myocardia damage to cardiac tissues including degeneration of cardiomyocytes, interstitial edema, infiltration of neutrophils, vacuolization of cardiomyocytes, damage muscle fibers, vascular congestion, and disruption of intercalated discs. These findings suggest that PS poses potential cardiac damage by promoting oxidative stress, stress-mediated inflammation, and apoptosis, ultimately resulting in functional and structural cardiac impairments.