Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.

Abstract

BACKGROUND:

Mitochondrial injury is a major cause of sepsis-induced organ failure. Polydatin (PD), a natural polyphenol, demonstrates protective mitochondrial effects in neurons and arteriolar smooth muscle cells during severe shock. In this study, we investigated the effects of PD on renal tubular epithelial cell (RTEC) mitochondria in a rat model of sepsis-induced acute kidney injury.

METHODS:

Rats underwent cecal ligation and puncture (CLP) to mimic sepsis-induced acute kidney injury. Rats were randomly divided into sham, CLP + normal saline, CLP + vehicle, and CLP + PD groups. Normal saline, vehicle, and 30 mg/kg PD were administered at 6, 12, and 18 hours after CLP or sham surgery via the tail vein. Mitochondrial morphology, metabolism, and function in RTECs were then assessed. Serum cytokines, renal function, survival, and histologic changes in the kidney were also evaluated.

RESULTS:

CLP increased lipid peroxide content, lysosomal instability, and opening of the mitochondrial permeability transition pore and caused mitochondrial swelling. Moreover, mitochondrial membrane potential (ΔΨm) was decreased and ATP levels reduced after CLP. PD inhibited all the above effects. It also inhibited the inflammatory response, improved renal function, attenuated histologic indicators of kidney damage, and prolonged survival.

CONCLUSIONS:

PD protects RTECs against mitochondrial dysfunction and prolongs survival in a rat model of sepsis-induced acute kidney injury. These effects may partially result from reductions in interleukin-6 and oxidative stress.

• Authors: Youguang Gao, Zhenhua Zeng, Tao Li, Siqi Xu, Xingmin Wang, Zhongqing Chen, Caizhu Lin
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 121 Issue 5 Pg. 1251-60 (Nov 2015) ISSN: 1526-7598 [Electronic] United States
• PMID: 26484460 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• Glucosides
• Stilbenes
• polydatin

Topics

• Acute Kidney Injury (drug therapy, etiology, pathology)
• Animals
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Epithelial Cells (drug effects, pathology, physiology)
• Glucosides (pharmacology, therapeutic use)
• Kidney Tubules (drug effects, pathology, physiology)
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Mitochondria (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Sepsis (complications, drug therapy, pathology)
• Stilbenes (pharmacology, therapeutic use)