Nephroprotective Role of Chrysophanol in Hypoxia/Reoxygenation-Induced Renal Cell Damage via Apoptosis, ER Stress, and Ferroptosis.

Chih-Hung Lin,Po-Chun Hsieh,Huan-Nung Chao,Han-Fang Tseng,Chou-Chin Lan,Chia-Chen Hsu,Ting-Yun Lin,Valeria Chiu,Chan-Yen Kuo,I-Shiang Tzeng

doi:10.3390/biomedicines9091283

Abstract

Acute kidney injury (AKI) is caused by hypoxia-reoxygenation (H/R), which is a kidney injury produced by a variety of causes, resulting in the remaining portion of the kidney function being unable to maintain the balance for performing the tasks of waste excretion metabolism, and electrolyte and acid-base balance. Many studies have reported the use of Chinese medicine to slow down the progression and alleviate the complications of chronic renal failure. Chrysophanol is a component of Rheum officinale Baill, a traditional Chinese medicine that has been clinically used to treat renal disease. We aimed to study the nephroprotective effect of chrysophanol on hypoxia/ reoxygenation (H/R)-induced cell damage. The results showed that chrysophanol prevented H/R-induced apoptosis via downregulation of cleaved Caspase-3, p-JNK, and Bax but upregulation of Bcl-2 expression. In contrast, chrysophanol attenuated H/R-induced endoplasmic reticulum (ER) stress via the downregulation of CHOP and p-IRE1α expression. Our data demonstrated that chrysophanol alleviated H/R-induced lipid ROS accumulation and ferroptosis. Therefore, we propose that chrysophanol may have a protective effect against AKI by regulating apoptosis, ER stress, and ferroptosis.

Highlights

It is well known that acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function that may further develop into chronic kidney disease (CKD)or even end-stage renal disease (ESRD) [1]
We investigated whether chrysophanol attenuated cell death in HK-2 cells exposed to H/R injury and exerted renal protection via modulation of apoptosis, endoplasmic reticulum (ER) stress, and ferroptosis
To further study whether chrysophanol attenuated H/R-induced cell death via apoptosis, we detected the expression of cleaved Caspase-3, Bax, and Bcl-2 in the presence of 30 μM chrysophanol under H/R conditions

Summary

Introduction

It is well known that acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function that may further develop into chronic kidney disease (CKD)or even end-stage renal disease (ESRD) [1]. It is well known that acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function that may further develop into chronic kidney disease (CKD). Biomedicines 2021, 9, 1283 medicine to slow down the progression and alleviate the complications of acute renal failure, thereby improving quality of life [2,3]. According to the literature on Chinese herbal intervention in AKI, Chinese herbs have been reported to play a critical role in the management of AKI by promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to CKD [5,6].

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