Protective effects of N-acetyl-cysteine in mitochondria bioenergetics, oxidative stress, dynamics and S-glutathionylation alterations in acute kidney damage induced by folic acid

Aparicio-Trejo, Omar Emiliano; Reyes-Fermín, Laura María; Briones-Herrera, Alfredo; Tapia, Edilia; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Sánchez‐Lozada, Laura G.; Pedraza‐Chaverrí, José

doi:10.1016/j.freeradbiomed.2018.11.005

Cited by 86 publications

(145 citation statements)

References 80 publications

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“…A role for NAC to protect acetaminophen inhibition of hepatic mitochondrial complex I activity as well as age‐related decline of oxidative phosphorylation in mice liver mitochondria has also been shown . Most importantly, our results are compatible with a very latest publication showing that NAC pretreatment was able to protect mitochondrial bioenergetics, redox state and dynamics alterations in folic acid‐induced AKI model, and this was related to its capacity to preserve the mitochondrial S‐glutathionylation and GSH levels . However, the regulatory role of NAC on mitochondrial homeostasis in the kidney are still not fully understood.…”

Section: Resultssupporting

confidence: 89%

“…Therefore, it is of interest to suggest that the antioxidant protection by NAC could be related to its capacity to preserve the S‐glutathionylation process, the reversible addition of glutathione to cysteine residues. Supporting to this suggestion is the evidence from recent study showing protective effects of NAC against S‐glutathionylation alteration in acute kidney damage induced by folic acid . In this regard, an additional interesting view that should be mentioned is that, apart from NAC, other similar compounds may also be useful in preventing this unfavorable effect of BPA on AKI.…”

Section: Resultsmentioning

confidence: 94%

“…It is also well tolerated and accepted as an effective drug to use in multiple clinical conditions with very low rate of adverse events. There is substantial evidence demonstrated the effectiveness of NAC in the protection against several AKI models including RIR and nephrotoxicity . Importantly, the protective role of NAC in BPA toxicity has recently been revealed in a rat model of BPA‐induced neurotoxicity .…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the protective role of NAC in BPA toxicity has recently been revealed in a rat model of BPA‐induced neurotoxicity . Furthermore, there are increasing research data supporting the advantage of NAC as an effective mitochondrial protective agent apart from its antioxidant potential . As oxidative stress and mitochondrial alterations are the hallmark of the pathogenesis in both AKI and BPA, we therefore examined the possible protection by NAC against any impacts of BPA in the kidneys after ischemia–reperfusion episode.…”

Section: Introductionmentioning

confidence: 99%

“…There is substantial evidence demonstrated the effectiveness of NAC in the protection against several AKI models including RIR 12 and nephrotoxicity. 13 Importantly, the protective role of NAC in BPA toxicity has recently been revealed in a rat model of BPA-induced neurotoxicity. 14 Furthermore, there are increasing research data supporting the advantage of NAC as an effective mitochondrial protective agent apart from its antioxidant potential.…”

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confidence: 99%

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Bisphenol A aggravates renal ischemia–reperfusion injury by disrupting mitochondrial homeostasis and N‐acetylcysteine mitigates the injurious outcomes

et al. 2019

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Exposure to bisphenol A (BPA), a chemical generally used in consumer products, becomes a global public health concern, as humans are increasingly exposed through their daily consuming activities. Renal ischemia–reperfusion (RIR) is the major cause of acute kidney injury with high prevalence and increased long‐term risks for multiple comorbidities and mortality. As the kidney is susceptible to these conditions, we explored whether the outcomes following the RIR episode could be influenced by BPA exposure, and investigated the therapeutic possibility by N‐acetylcysteine (NAC) including the mechanisms involved. Three groups of male Wistar rats were fed with vehicle, BPA 5, and 50 mg/kg, respectively, for five consecutive weeks then underwent the sham operation. Three other groups with identical treatment underwent bilateral renal IR induction (45‐min ischemia followed by 24‐hr reperfusion). An additional RIR group was treated with BPA 50 plus NAC 100 mg/kg. BPA‐exposed rats that encountered RIR episode showed dose‐dependent worsening of RIR injury as evidenced by augmentations of renal dysfunction and histopathological abnormalities, oxidative stress, apoptosis, mitochondrial functional impairment, mitochondrial dynamic, and mitophagy disproportion compared with the vehicle‐exposed RIR group. The NAC therapy considerably attenuated the exacerbated effects of BPA, which was associated with increased AMP‐activated protein kinase (AMPK), PGC‐1α, silent information regulator 3 or sirtuin 3 (SIRT3), and mitofusin 2 (MFN2) expressions but decreased Phosphorylated dynamin‐related protein 1 (p‐DRP1)/Dynamin‐related protein 1 (DRP1), PTEN‐induced putative kinase (PINK), and PARKIN expressions. These findings reveal the detrimental effect of repeated BPA exposure on the renal outcomes following the IR episode, and further demonstrate the protective efficacy of NAC by maintaining mitochondrial homeostasis, which is, partly, mediated through the AMPK‐PGC‐1α‐SIRT3 axis.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Bisphenol A aggravates renal ischemia–reperfusion injury by disrupting mitochondrial homeostasis and N‐acetylcysteine mitigates the injurious outcomes

et al. 2019

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Folic acid‐induced animal model of kidney disease

2021

Anim Models and Exp Med

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Kidney disease may be generally classified clinically into two categories: acute kidney injury (AKI) and chronic kidney disease (CKD), both of which are tightly interconnected. 1-3 AKI can often develop in clinical settings in critically ill patients, leading to increased morbidity and mortality. 4,5 AKI is manifested by a rapid decline in the glomerular filtration rates (GFRs) 6 and its pathogenesis is complex, involving ischemia, sepsis, drug toxicity, and trauma. 7 If left unmanaged, AKI can develop into CKD, which is characterized by a progressive decrease in GFR, culminating in a gradual loss of renal function. 8 The transition from AKI to CKD can also be hastened by numerous risk factors such as obesity, hypertension, diabetes, and chronic inflammation. 9-11 Currently, there are no effective treatments for either AKI or CKD, stressing a continual need to elucidate the underlying pathological mechanisms of AKI and CKD. In this regard, animal models of kidney disease have been invaluable in that utilization of these animal models not only facilitates our understanding of the

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Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction

et al. 2020

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Obstructive nephropathy favors the progression to chronic kidney disease (CKD), a severe health problem worldwide. The unilateral ureteral obstruction (UUO) model is used to study the development of fibrosis. Impairment of renal mitochondria plays a crucial role in several types of CKD and has been strongly related to fibrosis onset. Nevertheless, in the UUO model, the impairment of mitochondria, their relationship with endoplasmic reticulum (ER) stress induction and the participation of both to induce the fibrotic process remain unclear. In this review, we summarize the current information

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Protective effects of N-acetyl-cysteine in mitochondria bioenergetics, oxidative stress, dynamics and S-glutathionylation alterations in acute kidney damage induced by folic acid

Cited by 86 publications

References 80 publications

Bisphenol A aggravates renal ischemia–reperfusion injury by disrupting mitochondrial homeostasis and N‐acetylcysteine mitigates the injurious outcomes

Bisphenol A aggravates renal ischemia–reperfusion injury by disrupting mitochondrial homeostasis and N‐acetylcysteine mitigates the injurious outcomes

Folic acid‐induced animal model of kidney disease

Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction

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