N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q9/10 levels

Dludla, Phiwayinkosi V.; Orlando, Patrick; Silvestri, Sonia; Mazibuko-Mbeje, Sithandiwe E.; Johnson, Rabia; Marcheggiani, Fabio; Cirilli, Ilenia; Muller, Christo J. F.; Louw, Johan; Obonye, Nnini; Nyawo, Thembeka A.; Nkambule, Bongani B.; Tiano, Luca

doi:10.1016/j.toxrep.2019.11.004

Cited by 22 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, a reduction in one of the major antioxidants within the human body such as GSH has been consistent with the progression from NAFLD to NASH in some patients [ 83 ]. Hence, GSH is an increasing target of pharmacological compounds that have the capacity to enhance intracellular antioxidant defence systems [ 19 , 20 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…Many researchers, including our group, have focused on screening various pharmacological compounds for their ameliorative properties against the metabolic syndrome [ 19 , 20 , 21 , 22 ]. Over the years, it has become apparent that pharmacological interventions with strong antioxidant properties like N-acetyl cysteine (NAC) are essential in attenuating oxidative stress and inflammation in metabolic dysfunction.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

Self Cite

View full text Add to dashboard Cite

Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…There has been always a close relation between cardiotoxicity and elevated levels of oxidative stress biomarkers [ [28] , [29] , [30] ]. Oxidative stress initiates myocardial cell damage by stress activation of the ER associated with impaired mitochondrial function, resulting in severe cardiotoxicity [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin and simvastatin attenuate cisplatin-induced cardiotoxicity via disruption of endoplasmic reticulum stress-mediated apoptotic death in rats: targeting ER-Chaperone GRP78 and Calpain-1 pathways

2020

View full text Add to dashboard Cite

Cisplatin (CP) is a powerful antineoplastic chemotherapeutic agent with broad-spectrum properties. Acute and cumulative cardiotoxicity are major limiting factors for CP therapy. Various pathogenic pathways have been suggested to CP-induced cardiotoxicity; oxidative damage, ER stress, and programmed cell death/apoptosis. The present study aimed to assess the signaling mechanisms related to the advantageous effects of rosuvastatin (RSV) and simvastatin (SMV) against CP-related cardiac ER stress dependent apoptotic death in rats. Acute cardiotoxicity was induced by a single dose of CP (10 mg/kg, i.p.) on the 10th day of the experiment. RSV (10 mg/ kg/day) and SMV (10 mg/kg/day) were orally administered for 15 days. CP-treated rats showed significant alterations in electrocardiographic recordings and elevation in serum cardiac function biomarkers; troponin T content, lactate dehydrogenase and creatine kinase-MB levels as well as boost in the cardiac oxidative stress biomarkers. In addition, CP exposure resulted in GRP78 induction; an ER stress and elevation marker at calpain-1 content as well as activation of activated caspase-3 (ACASP3) and caspase-12 were reflected on CP-triggered apoptosis evidenced by elevation in the Bax/Bcl-2 ratio. However, RSV and SMV administration mitigate those adverse CP effects. Statins administration prominently alleviated CP-induced cardiac abnormalities exerting improvement in the ECG pattern and cardiac enzyme biomarkers. Interestingly, statins; RSV and SMV, disrupted CP-induced ER stress and the consequent apoptotic cell death evidenced by downregulation of ER-chaperone GRP78, calpain-1, ACASP3 and caspase-12 as well as decline in the Bax/Bcl-2 ratio. From all the previous findings, it can be suggested that statins namely; RSV and SMV, play protective role against CP-induced cardiac injury by regulating ER stress-mediated apoptotic pathways.

show abstract

“…One study investigated the 2.0 mM NAC and 200 μM α-tocopherol improved viability, approximately 40 % and 20 % respectively, against oxidative stress created by advanced glycation end products in SH-SY5Y cells [ 23 ]. NAC was reported to enhance endogenous coenzyme Q 9/10 levels, resulted in protecting against diabetes-induced cardiac injury [ 24 ]. NAC is also a well-known drug to treat patients with acute liver failure, and could protect the uterine tissue against sodium arsenite-induced oxidative stress in rats [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and apoptotic effects of copper and cadmium in the zebrafish liver cell line ZFL

Kwok

Chan

2020

Toxicology Reports

View full text Add to dashboard Cite

show abstract

N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q9/10 levels

Cited by 22 publications

References 33 publications

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Rosuvastatin and simvastatin attenuate cisplatin-induced cardiotoxicity via disruption of endoplasmic reticulum stress-mediated apoptotic death in rats: targeting ER-Chaperone GRP78 and Calpain-1 pathways

Oxidative stress and apoptotic effects of copper and cadmium in the zebrafish liver cell line ZFL

Contact Info

Product

Resources

About