Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets

Ntamo, Yonela; Ziqubu, Khanyisani; Chellan, Nireshni; Nkambule, Bongani B.; Nyambuya, Tawanda M.; Mazibuko-Mbeje, Sithandiwe E.; Gabuza, Kwazi B.; Orlando, Patrick; Tiano, Luca; Dludla, Phiwayinkosi V.

doi:10.1016/j.biopha.2022.112638

Cited by 13 publications

(6 citation statements)

References 86 publications

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“…Further, the notable concordance between the PheWAS results and the primary literature provides additional confidence in the strength and validity of the identified connection between NAC and ALF. Our findings are also concordant with recent discussions related to repurposing of NAC in various indications, including ALF ( 25 , 129 , 130 ).…”

Section: Discussionsupporting

confidence: 93%

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Jerome,

Zahn,

Abner

et al. 2024

Transl Gastroenterol Hepatol

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Background The World Health Organization (WHO)’s Essential Medicines List (EML) plays an important role in advocating for access to key treatments for conditions affecting people in all geographic settings. We applied our established drug repurposing methods to one EML agent, N-acetylcysteine (NAC), to identify additional uses of relevance to the global health community beyond its existing EML indication (acetaminophen toxicity). Methods We undertook a phenome-wide association study (PheWAS) of a variant in the glutathione synthetase ( GSS ) gene in approximately 35,000 patients to explore novel indications for use of NAC, which targets glutathione. We then evaluated the evidence regarding biologic plausibility, efficacy, and safety of NAC use in the new phenotype candidates. Results PheWAS of GSS variant R418Q revealed increased risk of several phenotypes related to non-acetaminophen induced acute liver failure (ALF), indicating that NAC may represent a therapeutic option for treating this condition. Evidence review identified practice guidelines, systematic reviews, clinical trials, retrospective cohorts and case series, and case reports. This evidence suggesting benefit of NAC use in this subset of ALF patients. The safety profile of NAC in this literature was also concordant with existing evidence on safety of this agent in acetaminophen-induced ALF. Conclusions This body of literature indicates efficacy and safety of NAC in non-acetaminophen induced ALF. Given the presence of NAC on the EML, this medication is likely to be available across a range of resource settings; promulgating its use in this novel subset of ALF can provide healthcare professionals and patients with a valuable and safe complement to supportive care for this disease.

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Section: Discussionsupporting

confidence: 93%

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Jerome,

Zahn,

Abner

et al. 2024

Transl Gastroenterol Hepatol

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“…Hepatic injury was usually accompanied by elevated AST and ALT 29 . NCTC1469 hepatocytes treated with Pb alone resulted in a significant increase in AST and ALT compared to the control group, indicating that Pb exposure could lead to hepatocyte injury.…”

Section: Discussionmentioning

confidence: 98%

Identification and preparation of selenium‐containing peptides from selenium‐enriched Pleurotus eryngii and their protective effect on lead‐induced oxidative damage in NCTC1469 hepatocytes

et al. 2023

J Sci Food Agric

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BACKGROUND Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium‐containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium‐containing peptide species were prepared from selenium‐enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium‐containing peptides on Pb‐induced oxidative stress in NCTC1469 hepatocytes. RESULTS Trypsin was selected as primary enzyme to hydrolyze the selenium‐enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5 h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed‐phase HPLC to obtain the selenium‐containing peptides SPH‐I‐2. Furthermore, SPH‐I‐2 was analyzed and a number of total 12 selenium‐containing peptides were identified by liquid chromatography‐tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium‐containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO‐1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium‐containing peptides were also able to suppress Pb‐induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. CONCLUSION The present study indicated that the selenium‐containing peptides could protect cells from Pb2+‐induced oxidative stress. © 2023 Society of Chemical Industry.

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“…This study has demonstrated that GFP reduces hepatic inflammation in T2DM rats; nevertheless, further investigation is required to determine the underlying mechanisms. Previous studies have reported that the mechanism of liver inflammation is related to hepatocyte steatosis, oxidative stress, and mitochondrial dysfunction(Gaul S et al, 2021) (Ntamo Y et al, 2022) (Zhang IW et al, 2022). However, the exact mechanism underlying liver inflammation varies depending on the etiology.…”

Section: Discussionmentioning

confidence: 99%

Grifola frondosa polysaccharide Ameliorates Inflammation and Insulin Resistance by Regulating Macrophage Polarization of liver in Type 2 diabetes mellitus Rats

Zou,

Li,

Wang

et al. 2024

Preprint

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Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterized by a lack of insulin secretion, insulin resistance (IR), and hyperglycemia. Given its high prevalence and multifarious complications, diabetes is globally ranked as the third leading cause of mortality. It is critical to discover efficient medication substitutes in order to lessen the drawbacks and adverse effects of traditional diabetes medication therapy. Previous studies have shown that Grifola frondosa polysaccharide (GFP) have the positive effects in regulating blood glucose and insulin resistance, but the understanding of its regulatory mechanism is still limited. Therefore, this study aimed to investigate the effects of GFP on liver inflammation induced by a high-fat diet (HFD) combined with streptozotocin (STZ) in type 2 diabetic rats and to explore its possible mechanisms. The results showed that GFP intervention reduced weight loss and hyperglycemia symptoms, as well as lowered FINS, HOMA-IR, IPGTT-AUC, and IPITT-AUC to different degrees in T2DM rats. At the same time, after GFP intervention, the secretion level of inflammatory factors (TNF-alpha, IL-1beta, MCP-1) was down-regulated and the secretion level of anti-inflammatory factor (IL-10) was up-regulated in the liver tissue of T2DM rats. Furthermore, GFP reduced macrophage infiltration in liver tissue, inhibited macrophage M1-type polarization, and promoted M2-type polarization. These results suggest that GFP intervention could attenuate the hepatic inflammatory response in T2DM rats; possible mechanisms for this effect include hepatic macrophage infiltration and M1/M2 polarization.

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Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets

Cited by 13 publications

References 86 publications

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Identification and preparation of selenium‐containing peptides from selenium‐enriched Pleurotus eryngii and their protective effect on lead‐induced oxidative damage in NCTC1469 hepatocytes

Grifola frondosa polysaccharide Ameliorates Inflammation and Insulin Resistance by Regulating Macrophage Polarization of liver in Type 2 diabetes mellitus Rats

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