Clemastine mitigates sepsis-induced acute kidney injury in rats; the role of α-Klotho/TLR-4/MYD-88/NF-κB/ Caspase-3/ p-P38 MAPK signaling pathways.

Sepsis is a fatal condition, with an annual incidence of more than 48 million cases as well as 11 million deaths resulting from it. Moreover, sepsis continues to rank as the fifth most prevalent cause of mortality globally. The objective of this study is to investigate if Clemastine (CLM) pretreatment protects against acute kidney injury (AKI) caused by cecal ligation and puncture (CLP) via modulating Toll-like receptor-4 (TLR-4), Myeloid differentiation primary response 88 (MYD-88), nuclear factor kappa B (NF-κB), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), and caspase-3 signaling pathways. CLM markedly attenuated sepsis-caused molecular, biochemical, and histopathological alterations. CLM downregulated the levels of the proinflammatory markers, suppressed the expression of cleaved caspase-3, TLR-4 and MYD-88 as well as inactivating NF-κB p-P65 and p-P38 proteins, inhibited Bax, NF-κB, and caspase-3 genes expression, and augmented α-Klotho protein expression as well as Bcl-2 gene expression. Finally, CLM pretreatment protected against acute kidney injury by preventing TLR-4/p-P38 pathway-mediated apoptotic cell death in rats.