Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria‐mediated apoptosis via SIRT1/p53 signalling

Zhang, Jiong; Zou, Yang; Cheng‐Jing, Yan; Lu, Xiaoyan; Wang, Xue‐Peng; Yu, Xiao‐Jia; Li, Guisen; Jia, Wang

doi:10.1111/jcmm.15782

Cited by 25 publications

(11 citation statements)

References 23 publications

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“…In this study, Rg1 pretreatment or pAD/Flag- AMPK α 1 stabilized MMP and reduced mPTP openness and mitochondrial Cyt C release to the cytosol (Figures 3 – 5 ). These results are consistent with previous reports [ 49 ]. More importantly, Rg1 pretreatment promoted mitochondrial respiratory chain complex NDUFB8 and UQCRC2 expression and ATP production.…”

Section: Discussionsupporting

confidence: 94%

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPKα1 Expression

Zhou

Zhao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5 ′ adenosine monophosphate-activated protein kinase α1 (AMPKα1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed. The results revealed that pretreatment with 25 μM Rg1 significantly increased NRK-52E viability, decreased lactate dehydrogenase (LDH) activity and apoptosis, suppressed reactive oxygen species generation and oxidative stress, stabilized mitochondrial membrane potential and reduced mitochondria permeability transition pore openness, decreased adenosine monophosphate/adenosine triphosphate ratio, and upregulated the expression of AMPKα1, cytochrome b-c1 complex subunit 2, NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8, and B-cell lymphoma 2, while downregulating BCL2-associated X protein expression. The effects of Rg1 pretreatment were similar to those of pAD/Flag-AMPKα1. After acute renal I/R injury, serum creatinine, blood urea nitrogen, LDH activity, and oxidative stress in renal tissue significantly increased. Rg1 pretreatment upregulated AMPKα1 expression, which protects against acute renal I/R injury by maintaining renal function homeostasis, inhibiting oxidative stress, and reducing apoptosis. Compound C, a specific inhibitor of AMPK, reversed the effects of Rg1. In summary, Rg1 pretreatment upregulated AMPKα1 expression, inhibited oxidative stress, maintained mitochondrial function, improved energy metabolism, reduced apoptosis, and ultimately protected renal tissue against acute renal I/R injury.

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Section: Discussionsupporting

confidence: 94%

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPKα1 Expression

Zhou

Zhao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that exerts anti-inflammatory and anti-oxidative effects on pathological process in several organs, including kidney 25 , 26 . In the present research, we found that TF inhibited CaOx-induced kidney oxidative stress injury and alleviated kidney crystal deposition by regulating miR-128/SIRT1 axis.…”

Section: Introductionmentioning

confidence: 99%

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1

Ye¹,

Yang²,

Liu³

et al. 2021

Int. J. Biol. Sci.

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Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress in vitro. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

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“…To further validate whether DBDCT induced apoptosis of HL7702 cells via the Gal-1-dependent pathway, the expressions of apoptosis-associated proteins in HL7702 cells were detected. e expressions of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax and p53 are crucial determinants of the apoptotic response mediated by many agents [38,39]. Accumulating evidence has shown that a decrease in the ratio of Bax/Bcl-2 inhibits Bax translocation to the mitochondria and then protects cells against apoptotic insults; however, a shift in the balance towards an excess of Bax evokes apoptosis [38,39].…”

Section: Discussionmentioning

confidence: 99%

Galectin‐1‐Dependent Mitochondria Apoptosis Plays an Essential Role in the Potential Protein Targets of DBDCT‐Induced Hepatotoxicity as Revealed by Quantitative Proteomic Analyses

Song

Ren

Liu

et al. 2022

Bioinorganic Chemistry and Applications

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Di-n-butyl-di-(4-chlorobenzohydroxamato) tin(IV) (DBDCT), a new patent agent, exhibited strong antitumor activity. In some cases, its activity was close to or even higher than cisplatin, a first-line clinical metallic agent. Similar to platinum compounds, it also showed toxicity. However, the effective targets and mechanisms for specific toxicity and biological activity are still unclear. In this study, proteomic analysis revealed that 146 proteins (98 upregulated and 48 downregulated) were differentially identified by label-free LC-MS/MS after DBDCT treatment. Meanwhile, network analysis of these differential proteins suggested that protein Galectin-1 (Gal-1) could regulate the apoptosis process (15 related proteins), which played an essential role in the potential targets of DBDCT-induced hepatotoxicity. Furthermore, it was demonstrated that DBDCT might promote ROS production, activate NF-κB p65, inhibit Ras and p-ERK1/2 expressions, increase the level of Gal-1, subsequently upregulate the expressions of Bax, p53, Fas, and FasL, and downregulate the expression of Bcl-2. As a result of these modulations, caspase cascades were finally activated, which executed apoptosis in HL7702 liver cells. Correspondingly, NAC (inhibitor of ROS), PDTC (inhibitor of NF-κB), EGF (ERK1/2 activator), and OTX008 (inhibitor of Gal-1) were found to reverse and abolish the DBDCT-associated cytotoxicity partially. In conclusion, Gal-1 might be the potential target for toxicity and biological activity. Moreover, the present study will lay the groundwork for future research about di-n-butyl-di-(4-chlorobenzohydroxamato) tin structure optimization and developing it into a new potential anticancer agent.

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Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria‐mediated apoptosis via SIRT1/p53 signalling

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 23 publications

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPKα1 Expression

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPKα1 Expression

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1

Galectin‐1‐Dependent Mitochondria Apoptosis Plays an Essential Role in the Potential Protein Targets of DBDCT‐Induced Hepatotoxicity as Revealed by Quantitative Proteomic Analyses

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