The equine placental extract ameliorates renal damage in mice with adenine-induced chronic kidney disease by inhibiting indoxyl sulfate production.
Abstract: Indoxyl sulfate (IS) is a dietary metabolite of tryptophan that is produced in the liver. It is a uremic toxin that facilitates the progression of chronic kidney disease (CKD). We previously observed that equine placental extract (ePE) inhibited IS synthesis in an inhibition assay using the liver S9 fraction. Unassigned: This 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. Unassigned: We assessed this effect through biochemical and histological analyses using a mouse model of CKD and an adenine diet, which induces renal damage through IS production. Unassigned: 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 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. Unassigned: These results suggest that ePE ameliorates IS-associated renal injury in adenine diet-fed mice by reducing IS production in the interstitium of the kidneys.
Publication Date: 2025-07-31 PubMed ID: 41036361PubMed Central: PMC12483479DOI: 10.5455/OVJ.2025.v15.i7.45Google Scholar: Lookup
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- Journal Article
Summary
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Overview
- This study investigates how equine placental extract (ePE) can protect against kidney damage by reducing the production of a harmful substance called indoxyl sulfate (IS) in a mouse model of chronic kidney disease (CKD).
Background
- Indoxyl sulfate (IS) is a toxin derived from tryptophan metabolism in the liver, accumulating in the body during CKD and aiding disease progression.
- Previous research found that ePE can inhibit the liver’s production of IS.
- CKD progression is often modeled in mice by feeding them an adenine-rich diet, which increases IS production and causes kidney damage.
Research Aim
- To explore how ePE affects kidney damage caused by adenine-induced CKD in mice, examining both tissue-level changes and molecular pathways.
- To understand the mechanism by which ePE influences IS production and related kidney injury.
Methodology
- Utilized a mouse model of CKD induced by an adenine diet, which promotes renal damage via elevated IS levels.
- Treated mice with equine placental extract (ePE) during the adenine diet regime.
- Conducted biochemical assays to measure IS levels in serum, kidney, and liver tissues.
- Performed histological analyses to assess kidney tissue damage using tubulointerstitial injury index and mesangial-positive cell area metrics.
- Used immunohistochemistry to detect inflammatory markers, notably F4/80-positive macrophages, in kidney interstitial tissue.
Key Findings
- ePE administration significantly lowered IS concentrations in blood serum, kidneys, and liver of mice on the adenine diet.
- Histological examination showed that ePE reduced kidney tissue damage, indicated by less tubulointerstitial injury and smaller mesangial-positive cell areas.
- ePE curtailed adenine-induced kidney fibrosis, which is a hallmark of CKD progression.
- Immunohistochemistry revealed that ePE decreased infiltration of F4/80-positive macrophages, cells involved in kidney inflammation.
Conclusions and Implications
- ePE protects against CKD-related kidney damage by inhibiting the production of indoxyl sulfate, thereby reducing its toxic effects.
- The reduction in IS levels correlates with decreased renal fibrosis and inflammation, suggesting ePE’s potential as a therapeutic agent in CKD management.
- This study highlights ePE’s dual role in biochemical inhibition of toxin synthesis and alleviation of kidney tissue injury in a CKD model.
Cite This Article
APA
Sugimoto K, Nakamura J, Deng D, Hirano E.
(2025).
The equine placental extract ameliorates renal damage in mice with adenine-induced chronic kidney disease by inhibiting indoxyl sulfate production.
Open Vet J, 15(7), 3334-3340.
https://doi.org/10.5455/OVJ.2025.v15.i7.45 Publication
Researcher Affiliations
- Research Institute, Japan Bio Products Co., Ltd.; 1-1 Kurume Research Center bldg., Fukuoka, Japan.
- Research Institute, Japan Bio Products Co., Ltd.; 1-1 Kurume Research Center bldg., Fukuoka, Japan.
- Research Institute, Japan Bio Products Co., Ltd.; 1-1 Kurume Research Center bldg., Fukuoka, Japan.
- Research Institute, Japan Bio Products Co., Ltd.; 1-1 Kurume Research Center bldg., Fukuoka, Japan.
- Medical Affairs Department, Japan Bio Products Co., Ltd., Tokyo, Japan.
MeSH Terms
- Animals
- Adenine / toxicity
- Indican / metabolism
- Indican / antagonists & inhibitors
- Mice
- Renal Insufficiency, Chronic / chemically induced
- Renal Insufficiency, Chronic / drug therapy
- Female
- Horses
- Placental Extracts / pharmacology
- Placental Extracts / therapeutic use
- Pregnancy
- Kidney / drug effects
- Kidney / pathology
- Male
Conflict of Interest Statement
All authors are employees of Japan Bio Products Co., Ltd. The authors declare no conflict of interest.
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