Rivastigmine attenuates LPS-induced cardiotoxicity via modulation of ER stress, oxidative pathways and apoptosis: Evidence from a rat model

This study aimed to investigate the potential protective effects of Rivastigmine (RIV) against lipopolysaccharide (LPS)-induced myocardial injury in rats, with a focus on inflammatory, endoplasmic reticulum (ER) stress, apoptotic, oxidative stress, and autophagy-related molecular markers. Thirty-two female Wistar albino rats were randomly assigned to four: (I) Control, (II) LPS, (III) LPS + RIV and (IV) RIV alone. Rats received 0.5–1 mL RIV and LPS 5 mg/kg intraperitoneally. After 24 h, the cardiac tissues were collected for histopathological evaluation. Immunohistochemical staining was performed for nuclear factor kappa beta (NF-κB), caspase-3 (Cas-3), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF). Gene expression analysis was also performed for endoplasmic reticulum chaperone BiP (GRP78), bcl-2-associated X (BAX), b-cell lymphoma-2 (BCL2), nuclear factor, erythroid 2-like 2 (NRF2), beclin 1 (BECLIN1), hypoxia-inducible factor-1α (HIF-1α) and sirtuin 1 (SIRT1). LPS administration resulted in significant myocardial damage, characterized by increased expression of GRP78, BAX, HIF-1α, NF-κB, and IL-6, and decreased expression of BCL2, NRF2, and SIRT1. Histopathological findings included cardiomyocyte degeneration, edema, and inflammatory infiltration. RIV treatment markedly attenuated these alterations, suppressed pro-inflammatory and apoptotic markers, and activated NRF2/SIRT1 and BECLIN1-mediated autophagy. RIV significantly reduced cardiomyocyte degeneration and improved histological scores compared to LPS-only rats ( p < 0.01). Reverse transcription-polymerase chain reaction showed significant downregulation of GRP78, BAX, and HIF-1α, while SIRT1, BCL2 and NRF2 expressions were markedly upregulated (all p < 0.05). Immunohistochemical staining revealed lower IL-6 and Cas-3 scores in the treatment group. These findings highlight RIV's potential as a cardioprotective agent in inflammatory conditions. • Rivastigmine attenuated LPS-induced myocardial inflammation and apoptosis. • RIV restored NRF2/SIRT1 and BECLIN1-mediated autophagy pathways. • RIV reduced ER stress marker GRP78 and pro-apoptotic gene BAX expression. • Histopathology showed reduced cardiomyocyte damage in RIV-treated rats. • RIV may be a potential cardioprotective agent in inflammatory heart injury.