Protective effect of taraxasterol on ischemia/reperfusion-induced acute kidney injury via inhibition of oxidative stress, inflammation, and apoptosis

Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.

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Loganin exerts a protective effect on ischemia–reperfusion‐induced acute kidney injury by regulating JAK2/STAT3 and Nrf2/HO‐1 signaling pathways

Drug Development Research ◽

10.1002/ddr.21853 ◽

2021 ◽

Author(s):

Fei Huang ◽

Xiang Wang ◽

Guifang Xiao ◽

Juan Xiao

Keyword(s):

Acute Kidney Injury ◽

Protective Effect ◽

Signaling Pathways ◽

Ischemia Reperfusion ◽

Kidney Injury

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The Circadian Clock Regulates the Expression of the Nuclear Factor Erythroid 2-Related Factor 2 in Acute Kidney Injury following Myocardial Ischemia-Reperfusion in Diabetic Rat

BioMed Research International ◽

10.1155/2021/6683779 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Chong Dong ◽

Cheng Zeng ◽

Li Du ◽

Qian Sun

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Myocardial Ischemia ◽

Circadian Clock ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Diabetic Rat ◽

Related Factor ◽

Nuclear Factor ◽

Myocardial Ischemia Reperfusion

Cardiac surgery-associated acute kidney injury (AKI) is a serious and frequent complication with poor prognosis, and disruption in circadian rhythm shall adversely influence cardiovascular and renal functions via oxidative stress mechanisms. However, the role of circadian clock genes (circadian locomotor output cycle kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1)) and its interaction with nuclear factor erythroid 2-related factor 2 (Nrf2) in AKI following myocardial ischemia-reperfusion (MIR) in the diabetic rat has not yet been explored. In this study, rats were divided into the sham (S) group, MIR (M) group, diabetic (D) group, and diabetic+MIR (DM) group. At light (zeitgeber time (ZT) 0) and dark time points (ZT12), rat MIR model was established by occlusion of the left anterior descending coronary artery for 30 min followed by 2 -hour reperfusion, and then renal injury was evaluated. The renal histological changes in the DM group were significantly high compared to other groups; serum creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin levels, as well as malondialdehyde and 8-iso-prostaglandin-F2α levels in renal tissues of M ZT12 and DM ZT12 subgroups, were significantly higher than those of M ZT0 and DM ZT0 subgroups, individually indicating increased oxidative stress at a dark cycle. Further, Nrf2 protein accumulated in a circadian manner with decreasing levels at night in the DM and M groups. In conclusion, renal injury following MIR was exacerbated in the diabetic rat at night through molecular mechanisms involving transcriptional control of the circadian clock on light-dark activation of Nrf2.

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Perilipin 2 Impacts Acute Kidney Injury via Regulation of PPARα

Journal of Immunology Research ◽

10.1155/2021/9972704 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Sujuan Xu ◽

Edward Lee ◽

Zhaoxing Sun ◽

Xiaoyan Wang ◽

Ting Ren ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Acute Kidney Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Tumors ◽

Tubular Cells ◽

Proximal Tubular ◽

Perilipin 2 ◽

Renal Proximal Tubular

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.

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