Dexpanthenol protects against lipopolysaccharide-induced acute kidney injury by restoring aquaporin-2 levels via regulation of the silent information regulator 1 signaling pathway

Abstract

Background Acute kidney injury (AKI) is a serious pathology that causes dysfunction in concentrating urine due to kidney damage, resulting in blood pressure dysregulation and increased levels of toxic metabolites. Dexpanthenol (DEX), a pantothenic acid analog, exhibits anti-inflammatory and anti-apoptotic properties in various tissues. This study investigated the protective effects of DEX against systemic inflammation-induced AKI. Methods Thirty-two female rats were randomly assigned to the control, lipopolysaccharide (LPS), LPS+DEX, and DEX groups. LPS (5 mg/kg, single dose on the third day, 6 h before sacrifice) and DEX (500 mg/kg/day for 3 days) were administered intraperitoneally. After sacrifice, blood samples and kidney tissues were collected. Hematoxylin and eosin, caspase-3 (Cas-3), and tumor necrosis factor alpha (TNF-α) staining were performed on the kidney tissues. The total oxidant status (TOS) and total antioxidant status were measured using spectrophotometric methods. Aquaporin-2 (AQP-2), silent information regulator 1 (SIRT1), and interleukin-6 (IL-6) were detected using quantitative reverse transcription-polymerase chain reaction analysis. Results Histopathological analysis revealed that DEX treatment ameliorated histopathological changes. In the LPS group, an increase in the blood urea nitrogen, creatinine, urea, IL-6, Cas-3, TNF-α, and TOS levels and oxidative stress index was observed compared with the control group, whereas AQP-2 and SIRT1 levels decreased. DEX treatment reversed these effects. Conclusions DEX was found to effectively prevent inflammation, oxidative stress, and apoptosis in the kidneys via the SIRT1 signaling pathway. These protective properties suggest DEX’s potential as a therapeutic agent for the treatment of kidney pathologies.

Keywords

• apoptosis
• caspase 3
• dexpanthenol
• kidney
• oxidative stress
• sirtuin 1