Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

Zhang, Mei; Yuan, Jing; Dong, Rong; Da, Jingjing; Li, Qian; Hu, Ying; Yu, Fangfang; Yan, Ran; Zha, Yan; Long, Yun

doi:10.1515/biol-2021-0054

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Our previous studies have shown that HHcy can aggravate AKI induced by ischemia-reperfusion or cisplatin ( Zhang et al, 2021 ). However, the specific pathogenesis is still unclear.…”

Section: Resultsmentioning

confidence: 99%

Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage

Zhang

Dong

et al. 2022

Front. Physiol.

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Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.

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“…Our previous studies have shown that HHcy can aggravate AKI induced by ischemia-reperfusion or cisplatin ( Zhang et al, 2021 ). However, the specific pathogenesis is still unclear.…”

Section: Resultsmentioning

confidence: 99%

Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage

Zhang

Dong

et al. 2022

Front. Physiol.

Self Cite

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“…Hyperhomocysteine (HHcy) predicts renal functional decline in hypertensive adults [ 21 ], and accelerates AKI to CKD progression [ 22 ]. The pathogenic mechanisms of Hcy include oxidative stress, inflammation, endoplasmic reticulum stress [ 20 ], and mitochondrial damage [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Uremic Toxin Homocysteine Exacerbates the Brain Inflammation Induced by Renal Ischemia-Reperfusion in Mice

Park

Dusabimana

et al. 2022

Biomedicines

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Homocysteine (Hcy), a homologue of cysteine, is biosynthesized during methionine metabolism. Elevated plasma Hcy is associated with glomerular injury and considered as a risk factor for renal dysfunction, predicting incident chronic kidney disease. Hcy promotes oxidative stress, inflammation, and endothelial dysfunction. Acute kidney injury (AKI) is defined as a sudden decline in renal function and is important clinically due to the high mortality rate in AKI patients with multiple organs failure, including the brain. However, the cytotoxic role of Hcy on the brain following AKI is not directly shown. In this study, C57BL/6 mice were subjected to renal ischemia reperfusion (IR), one of the causes of AKI, and treated with vehicle or Hcy (0.2 mg/kg) to analyse the brain inflammation. IR mice showed a significant induction in plasma creatinine and Hcy levels, associated with tubular injury and neutrophil infiltration, and upregulation of pro-inflammatory cytokines and tubular apoptosis. Hcy treatment aggravated these renal damage and dysfunction by regulating cyclooxygenase-2 (COX-2), inhibitor of κB phosphorylation, and heme oxygenase-1. Consistently, Hcy treatment significantly increased expression of pro-inflammatory cytokines, glial fibrillary acidic protein, and COX-2 in the prefrontal cortex of IR mice. We conclude that Hcy treatment aggravated the renal dysfunction and enhanced IR-induced inflammatory cytokines and astrocyte activation in the brain. We propose that lowering plasma Hcy levels may attenuate neurological dysfunction found in patients with AKI.

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“…After reperfusion of blood flow to the ischemic tissues, severe metabolic derangement and tissue structural destruction are observed. IRI is one of the acute renal injuries with a significant mortality and morbidity rate, which mainly manifests as rapid decompensation of renal function ( Zhang et al, 2021 ). It is a complicated pathophysiological process caused by several things that interfere with blood circulation, such as surgery on the urinary and cardiovascular systems, organ transplantation, trauma, shock, and thrombus ( Thapa et al, 2022 ).…”

Section: Dna Damage In Renal Diseasesmentioning

confidence: 99%

Roles of DNA damage in renal tubular epithelial cells injury

et al. 2023

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The prevalence of renal diseases including acute kidney injury (AKI) and chronic kidney disease (CKD) is increasing worldwide. However, the pathogenesis of most renal diseases is still unclear and effective treatments are still lacking. DNA damage and the related DNA damage response (DDR) have been confirmed as common pathogenesis of acute kidney injury and chronic kidney disease. Reactive oxygen species (ROS) induced DNA damage is one of the most common types of DNA damage involved in the pathogenesis of acute kidney injury and chronic kidney disease. In recent years, several developments have been made in the field of DNA damage. Herein, we review the roles and developments of DNA damage and DNA damage response in renal tubular epithelial cell injury in acute kidney injury and chronic kidney disease. In this review, we conclude that focusing on DNA damage and DNA damage response may provide valuable diagnostic biomarkers and treatment strategies for renal diseases including acute kidney injury and chronic kidney disease.

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Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

Cited by 4 publications

References 21 publications

Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage

Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage

The Uremic Toxin Homocysteine Exacerbates the Brain Inflammation Induced by Renal Ischemia-Reperfusion in Mice

Roles of DNA damage in renal tubular epithelial cells injury

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