Melatonin Attenuates Mitochondrial Damage in Aristolochic Acid-Induced Acute Kidney Injury

Authors

Jian Sun
Jinjin Pan
Qinlong Liu
Jizhong Cheng
Qing Tang
Yuke Ji
Ke Cheng
Rui Wang
Liang Liu
Dingyou Wang
Na Wu
Xu Zheng
Junxia Li
Xueyan Zhang
Zhilong Zhu
Yanchun Ding
Feng Zheng
Jia Li
Ying Zhang
Yuhui Yuan

Publication Date

1-1-2023

Journal

Biomolecules & Therapeutics

DOI

10.4062/biomolther.2022.054

PMID

36097885

PMCID

PMC9810451

PubMedCentral® Posted Date

9-13-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Melatonin, Aristolochic acid, Acute kidney injury, Mitochondrial damage, Mitophagy, Oxidative stress

Abstract

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities