{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:43:23Z","timestamp":1791614603896,"version":"4.3.4"},"reference-count":89,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["117829"],"award-info":[{"award-number":["117829"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 (PPAR\u03b3). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1\u03b2, tumour necrosis factor alpha (TNF-\u03b1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB). 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.<\/jats:p>","DOI":"10.3390\/antiox9121283","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T09:21:15Z","timestamp":1608110475000},"page":"1283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5965-3610","authenticated-orcid":false,"given":"Phiwayinkosi V.","family":"Dludla","sequence":"first","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bongani B.","family":"Nkambule","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sithandiwe E.","family":"Mazibuko-Mbeje","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Natural and Agricultural Sciences, North-West University, Mmabatho 2745, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-9524","authenticated-orcid":false,"given":"Tawanda M.","family":"Nyambuya","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"},{"name":"Department of Health Sciences, Faculty of Health and Applied Sciences, Namibia University of Science and Technology, Windhoek 9000, Namibia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-7525","authenticated-orcid":false,"given":"Fabio","family":"Marcheggiani","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-5426","authenticated-orcid":false,"given":"Ilenia","family":"Cirilli","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"},{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khanyisani","family":"Ziqubu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Natural and Agricultural Sciences, North-West University, Mmabatho 2745, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-4673","authenticated-orcid":false,"given":"Samukelisiwe C.","family":"Shabalala","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-0789","authenticated-orcid":false,"given":"Rabia","family":"Johnson","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Louw","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Damiani","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-7106","authenticated-orcid":false,"given":"Luca","family":"Tiano","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.reprotox.2016.10.001","article-title":"Metabolism disrupting chemicals and metabolic disorders","volume":"68","author":"Heindel","year":"2017","journal-title":"Reprod. 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