The equine placental extract ameliorates renal damage in mice with adenine-induced chronic kidney disease by inhibiting indoxyl sulfate production

Background: Indoxyl sulfate (IS) is a dietary metabolite of tryptophan produced in the liver. It is a uraemic toxin that facilitates the progression of chronic kidney disease (CKD). Previously, we had observed that equine placental extract (ePE) inhibited IS synthesis in an in vitro inhibition assay using the liver S9 fraction. Aim: The study was designed to investigate the effects of ePE on adenine-induced renal failure in mice at the histological and molecular levels to understand the mechanism of action of ePE. Methods: We assessed this effect through biochemical and histological in vivo analyses, using a CKD mouse and an adenine diet models, which induced renal damage through IS production. Results: ePE significantly suppressed serum, renal, and hepatic IS production in adenine diet-fed mice by inhibiting IS synthesis. Histological and semi-quantitative analyses using the tubulointerstitial injury index (TII) revealed that ePE effectively prevented the increase in adenine-induced mesangial-positive cell area. Additionally, ePE administration significantly suppressed adenine-induced renal fibrosis in mice. Moreover, immunohistochemical analysis demonstrated that ePE administration reduced the accumulation of F4/80-positive macrophages in the interstitial inflammatory infiltrates. Conclusion: These results suggest that ePE could ameliorate IS-associated renal injury in adenine diet-fed mice by reducing IS production in the interstitium of the kidneys. Published by Eldaghayes Publisher.

Keywords: Equine placental extract, Renal failure, Tubulointerstitial injury, Uremic toxin.