Ergosterol alleviates lipopolysaccharide-induced acute kidney injury in rats via a mechanistic modulation of TLR4/p-p38/NF-κB, iNOS/NO and Nrf2/HO-1 signaling pathways.

UNLABELLED: Acute kidney injury (AKI) frequently complicates sepsis, contributing to long-term disability and high mortality rates. Thus, effective preventive and therapeutic methods are highly recommended. Recently, phytosterols have attracted attention due to their potential in preventing and treating various diseases. Therefore, our study aimed to explore the renoprotective effects of ergosterol (ER), a member of the phytosterol family, in a lipopolysaccharide (LPS)-induced AKI rat model.

METHODS: 32 adult male rats were divided into: control, ER and AKI without and with ER administration groups. Serum samples were analyzed for creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), reduced glutathione (GSH), tumor necrosis factor- α (TNF-α), interleukin 1-β (IL-1β), and IL-18 levels. Renal tissues were assessed for malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and cyclo-oxygenase 2 (COX-2) levels. Renal expressions of Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 (HO-1) were determined. Western blot analysis was conducted to estimate renal levels of phosphorylated p38 (p-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2). Histological examination and immunohistochemical assessment of nuclear factor kappa B (NF-κB) and caspase 3 were performed.

RESULTS: Treatment of AKI rats with ER led to significant attenuation of renal inflammation and injury that was evidenced by the significant downregulation of TLR4/p-p38/NF-κB and iNOS/NO signaling pathways, along with upregulation of Nrf2/HO-1 pathway compared to AKI group. These changes were associated with substantial improvements in renal functions and histological damage.

CONCLUSION: Administration of ergosterol has ameliorated the development of LPS-induced AKI in rats.