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

Dludla, Phiwayinkosi V.; Nkambule, Bongani B.; Mazibuko-Mbeje, Sithandiwe E.; Nyambuya, Tawanda M.; Marcheggiani, Fabio; Cirilli, Ilenia; Ziqubu, Khanyisani; Shabalala, Samukelisiwe; Johnson, Rabia; Louw, Johan; Damiani, Elisabetta; Tiano, Luca

doi:10.3390/antiox9121283

Cited by 40 publications

(26 citation statements)

References 80 publications

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“…However, in our study, NAC overdose (N800) induced liver steatosis and dramatically increased hepatic TG levels at 48 h post-NAC injection. On the other hand, NAC has been reported to block hepatic lipid accumulation in preclinical models of NAFLD [ 51 ]. In rodent disease models, NAC neutralizes oxidative stress by providing GSH, thereby reducing the development of diseases.…”

Section: Discussionmentioning

confidence: 99%

N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

et al. 2021

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Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients who failed in standard treatment. This study explores the toxicity of NAC overdose in both APAP poisoning and normal mice. Two inbred mouse strains with different sensitivities to propacetamol-induced hepatotoxicity (PIH) were treated with different NAC doses. NAC therapy decreased PIH by reducing lipid oxidation, protein nitration and inflammation, and increasing glutathione (GSH) levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH were dose-dependent from 125 (N125) to 275 mg/kg (N275). Elevated doses of NAC (400 and 800 mg/kg, N400 and N800) caused additional deaths in both propacetamol-treated and normal mice. N800 treatments significantly decreased hepatic GSH levels and induced inflammatory cytokines and hepatic microvesicular steatosis in both propacetamol-treated and normal mice. Furthermore, both N275 and N400 treatments decreased serum triglyceride (TG) and induced hepatic TG, whereas N800 treatment significantly increased interleukin-6, hepatic TG, and total cholesterol levels. In conclusion, NAC overdose induces hepatic and systemic inflammations and interferes with fatty acid metabolism.

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Section: Discussionmentioning

confidence: 99%

N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

et al. 2021

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“…Nonalcoholic fatty liver disease (NAFLD) can manifest as simple steatosis or progress to chronic liver damage, due to the increased hepatic flow of free fatty acids, which generates an increase in oxidative stress concomitant with the suppression of intracellular antioxidant activity. Evidence from experimental studies has revealed that NAC blocks the accumulation of liver lipids and reduces proinflammatory markers, such as IL-6 and IL-1β, TNF-α, and NF-κB [ 159 ].…”

Section: Clinical Indicationsmentioning

confidence: 99%

N-Acetylcysteine (NAC): Impacts on Human Health

et al. 2021

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N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

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“…There is evidence that NAC may block hepatic lipid accumulation and provide therapeutic benefit against metabolic complications found in nonalcoholic fatty liver disease (NAFLD). This is primarily due to the antioxidant effects and attenuation of lipid peroxidation [ 64 ]. This is supported by most preclinical studies and a few clinical studies, and there is an urgent need for larger clinical studies.…”

Section: Metabolic Syndrome Including Nonalcoholic Fatty Liver Disease Diabetes and Polycystic Ovarymentioning

confidence: 99%

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

Schwalfenberg

2021

Journal of Nutrition and Metabolism

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Objective. To review the clinical usefulness of N-acetylcysteine (NAC) as treatment or adjunctive therapy in a number of medical conditions. Use in Tylenol overdose, cystic fibrosis, and chronic obstructive lung disease has been well documented, but there is emerging evidence many other conditions would benefit from this safe, simple, and inexpensive intervention. Quality of Evidence. PubMed, several books, and conference proceedings were searched for articles on NAC and health conditions listed above reviewing supportive evidence. This study uses a traditional integrated review format, and clinically relevant information is assessed using the American Family Physician Evidence-Based Medicine Toolkit. A table summarizing the potential mechanisms of action for N-acetylcysteine in these conditions is presented. Main Message. N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases. These conditions include polycystic ovary disease, male infertility, sleep apnea, acquired immune deficiency syndrome, influenza, parkinsonism, multiple sclerosis, peripheral neuropathy, stroke outcomes, diabetic neuropathy, Crohn’s disease, ulcerative colitis, schizophrenia, bipolar illness, and obsessive compulsive disorder; it can also be useful as a chelator for heavy metals and nanoparticles. There are also a number of other conditions that may show benefit; however, the evidence is not as robust. Conclusion. The use of N-acetylcysteine should be considered in a number of conditions as our population ages and levels of glutathione drop. Supplementation may contribute to reducing morbidity and mortality in some chronic conditions as outlined in the article.

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

Cited by 40 publications

References 80 publications

N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

N-Acetylcysteine (NAC): Impacts on Human Health

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

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