Extraintestinal Manifestations in Induced Colitis: Controversial Effects of N -Acetylcysteine on Colon, Liver, and Kidney

被引:4
作者
Da Paz Martins A.S. [1 ]
De Andrade K.Q. [2 ]
De Araújo O.R.P. [3 ]
Da Conceição G.C.M. [3 ]
Da Silva Gomes A. [2 ]
Goulart M.O.F. [1 ,3 ,4 ]
Moura F.A. [2 ,5 ]
机构
[1] Doctoral Program of the Northeast Biotechnology Network, Federal University of Alagoas, Alagoas, Maceió
[2] College of Nutrition, Federal University of Alagoas, Alagoas, Maceió
[3] Institute of Chemistry and Biotechnology, Federal University of Alagoas, Alagoas, Maceió
[4] Institute of Biological and Health Sciences, Federal University of Alagoas, Alagoas, Maceió
[5] College of Medicine, Federal University of Alagoas, Alagoas, Maceió
关键词
All Open Access; Gold;
D O I
10.1155/2023/8811463
中图分类号
学科分类号
摘要
Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N-acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38th day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H2O2)) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF-α, and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF-α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease. © 2023 Amylly Sanuelly da Paz Martins et al.
引用
收藏
相关论文
共 81 条
  • [11] Dos Santos Tenorio M.C., Graciliano N.G., Moura F.A., De Oliveira A.C.M., Goulart M.O.F., N -acetylcysteine (NAC): Impacts on human health, Antioxidants, 10, 6, (2021)
  • [12] De Andrade K.Q., Moura F.A., Dos Santos J.M., De Araujo O.R.P., De Farias Santos J.C., Goulart M.O.F., Oxidative stress and inflammation in hepatic diseases: Therapeutic possibilities of N -acetylcysteine, International Journal of Molecular Sciences, 16, 12, pp. 30269-30308, (2015)
  • [13] Zhitkovich A., N -acetylcysteine: Antioxidant, aldehyde scavenger, and more, Chemical Research in Toxicology, 32, 7, pp. 1318-1319, (2019)
  • [14] Olsson B., Johansson M., Gabrielsson J., Bolme P., Pharmacokinetics and bioavailability of reduced and oxidized N -acetylcysteine, European Journal of Clinical Pharmacology, 34, pp. 77-82, (1988)
  • [15] Pedre B., Barayeu U., Ezerina D., Dick T.P., The mechanism of action of N -acetylcysteine (NAC): The emerging role of H<sub>2</sub>S and sulfane sulfur species, Pharmacology & Therapeutics, 228, (2021)
  • [16] Guijarro L.G., Mate J., Gisbert J.P., Perez-Calle J.L., Marin-Jimenez I., Arriaza E., Olleros T., Delgado M., Castillejo M.S., Prieto-Merino D., Lara V.G., Pena A.S., N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized, placebo-controlled pilot study, World Journal of Gastroenterology, 14, 18, pp. 2851-2857, (2008)
  • [17] Shirazi K.M., Sotoudeh S., Shirazi A.M., Moaddab S.-Y., Nourpanah Z., Nikniaz Z., Effect of N -acetylcysteine on remission maintenance in patients with ulcerative colitis: A randomized, double-blind controlled clinical trial, Clinics and Research in Hepatology and Gastroenterology, 45, 4, (2021)
  • [18] Borgstrom L., Kagedal B., Dose dependent pharmacokinetics of N -acetylcysteine after oral dosing to man, Biopharmaceutics & Drug Disposition, 11, 2, pp. 131-136, (1990)
  • [19] Pick E., Keisari Y., A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture, Journal of Immunological Methods, 38, 1-2, pp. 161-170, (1980)
  • [20] Aebi H., Catalase in vitro, Oxygen Radicals in Biological Systems, 105, pp. 121-126, (1984)