MMSL 2023, 92(3):194-207 | DOI: 10.31482/mmsl.2022.039

EVALUATION OF THE EFFECTS OF N-ACETYLCYSTEINE ON SERUM GLUCOSE, LIPID PROFILE, AND BODY WEIGHT IN RATS WITH FRUCTOSE-INDUCED METABOLIC SYNDROMEOriginal article

Auss Z. Yahya ORCID...1*, Ghada A. Taqa ORCID...2, Muhammad A. Alkataan ORCID...3
1 Ministry of Health, Ninevah Heath Directorate, Mosul, Iraq
2 Department of Dental Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq
3 Department of Biochemistry, College of Medicine, University of Ninevah, Mosul, Iraq

Background: Overconsumption of fructose may cause metabolic syndrome (MetS). MetS pathogenesis is caused by oxidative stress, cellular malfunction, and systemic inflammation caused by hereditary and environmental factors. N-acetylcysteine (NAC) has become associated with the phrase "antioxidant." Most researchers use and test NAC with the goal of preventing or reducing oxidative stress.

Aim: To determine the positive effects of NAC on blood glucose, lipid profile, and body weight in fructose-induced metabolic syndrome in albino rats.

Materials and Methods: Forty male albino rats, 10-12 weeks old, were haphazardly divided into five groups of identical size. Group I (negative control) received tap water for 12 weeks. Group II (positive control) received a 60% w/w fructose solution (60% FS) instead of tap water for 12 weeks. Group III (NAC) received tap water and an intra-peritoneal (IP) injection of NAC (150 mg/kg/day) for 12 weeks. Group IV (protection) co-administered 60% FS orally and NAC IP injection (150 mg/kg/day) for 12 weeks. Group V (treatment) received 60% FS for 8 weeks followed by 4 weeks of drinking tap water with NAC IP injection (150 mg/kg/day). Blood samples were taken at weeks 0, 8, and 12 and were tested for serum glucose and lipid profile. All animals of each group were weighted at weeks 0, 8 and 12 of the study.

Results: Concerning serum glucose, group II showed increased glycaemia at week 8 and further elevation during week 12. Group III displayed normal glycaemia at weeks 8 and 12. In group IV, glycaemia showed elevation at week 8 followed by almost complete restoration at week 12. In group V, there was an increased glycaemia at week 8 followed by a partial restoration at week 12. Regarding lipid profile parameters, group II demonstrated a deterioration during week 8 and more worsening during week 12. There were no significant changes in group III's parameters during weeks 8 and 12. Group IV displayed a worsening in lipid profile during week 8 followed by a nearly complete improvement during week 12. During week 8, group V deteriorated, followed by a partial recovery during week 12. Concerning body weight, group II showed a weight gain at week 8 and further elevation during week 12. Group III displayed normal glycaemia at weeks 8 and 12. In group IV, glycaemia showed elevation at week 8 followed by almost complete restoration at week 12. In group V, there was an increased glycaemia at week 8 followed by a partial restoration at week 12. At week 8, there was a significant elevation in body weights  in groups II and V compared to group I. Moreover, a significant reduction in body weight was recorded in group IV compared to group II during week 8. At week 12, a significant elevation in body weight was noticed  in groups II and V compared to group I. Moreover, there was a significant reduction in body weight in group III compared to group I. On the other hand, there was a significant fall in body weight in groups IV and V  compared to group II during week 12.

Conclusion: MetS was caused by a high-fructose diet, which has been shown to have a negative impact on serum glucose, lipid profiles, and body weight. Moreover, NAC has been shown to enhance these parameters in a time-dependent manner.

Keywords: N-acetylcysteine; Fructose; Antioxidants; Metabolic syndrome; Serum glucose; Lipid profile; Body weight

Received: June 5, 2022; Revised: August 8, 2022; Accepted: August 24, 2022; Prepublished online: January 5, 2023; Published: September 1, 2023  Show citation

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Yahya, A.Z., Taqa, G.A., & Alkataan, M.A. (2023). EVALUATION OF THE EFFECTS OF N-ACETYLCYSTEINE ON SERUM GLUCOSE, LIPID PROFILE, AND BODY WEIGHT IN RATS WITH FRUCTOSE-INDUCED METABOLIC SYNDROME. MMSL92(3), 194-207. doi: 10.31482/mmsl.2022.039
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References

  1. Wong SK, Chin KY, Suhaimi FH, et al. Animal models of metabolic syndrome: a review. Nutrition & metabolism. 2016 Dec;13(1):1-2. https://doi.org/10.1186/s12986-016-0123-9. Go to original source... Go to PubMed...
  2. El-Mehi AE, Faried MA. Effect of high-fructose diet-induced metabolic syndrome on the pituitary-gonadal axis from adolescence through adulthood in male albino rats and the possible protective role of ginger extract. A biochemical, histological and immunohistochemical study. Folia morphologica. 2020;79(4):690-708. https://doi.org/10.5603/fm.a2019.0139. Go to original source... Go to PubMed...
  3. Wong WY, Brown L. Induction of metabolic syndrome by excess fructose consumption. diabetic Cardiomyopathy 2014 (pp. 41-63). Springer, New York, NY. http://dx.doi.org/10.1007/978-1-4614-9317-4_3. Go to original source...
  4. Goswami K, Gandhe M. Evolution of metabolic syndrome and its biomarkers. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2018 Nov 1;12(6):1071-1074. https://doi.org/10.1016/j.dsx.2018.06.027. Go to original source... Go to PubMed...
  5. Kaur J. A comprehensive review on metabolic syndrome. Cardiology research and practice. 2014 Oct; 2014. https://doi.org/10.1155/2014/943162. Go to original source... Go to PubMed...
  6. Mendrick DL, Diehl AM, Topor LS, et al. Metabolic syndrome and associated diseases: from the bench to the clinic. Toxicological Sciences. 2018 Mar 1;162(1):36-42.https://doi.org/10.1093/toxsci/kfx233. Go to original source... Go to PubMed...
  7. Kim MS, Wang Y, Rodrigues B. Lipoprotein lipase mediated fatty acid delivery and its impact in diabetic cardiomyopathy. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2012 May 1;1821(5):800-808. https://doi.org/10.1016/j.bbalip.2011.10.001. Go to original source... Go to PubMed...
  8. Fuchs T, Loureiro MD, Macedo LE, et al. Animal models in metabolic syndrome. Revista do Colégio Brasileiro de Cirurgiões. 2018 Oct 29;45. https://doi.org/10.1590/0100-6991e-20181975. Go to original source... Go to PubMed...
  9. Baena M, Sangüesa G, Dávalos A, et al. (2016). Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues. Scientific reports, 6(1), 1-15. https://doi.org/10.1038/srep26149. Go to original source... Go to PubMed...
  10. Vona R, Gambardella L, Cittadini C, et al. Biomarkers of oxidative stress in metabolic syndrome and associated diseases. Oxidative medicine and cellular longevity. 2019 Oct;2019. https://doi.org/10.1155/2019/8267234. Go to original source... Go to PubMed...
  11. Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X, et al. Metabolic syndrome is associated with oxidative stress and proinflammatory state. Antioxidants. 2020 Mar;9(3):236. https://doi.org/10.3390/antiox9030236. Go to original source... Go to PubMed...
  12. Bateman DN, Dear JW. Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use. Toxicology research. 2019 Jul 1;8(4):489-498. https://doi.org/10.1039/c9tx00002j. Go to original source... Go to PubMed...
  13. Dludla PV, Nkambule BB, Mazibuko-Mbeje SE, et al. N-acetyl cysteine targets hepatic lipid accumulation to curb oxidative stress and inflammation in NAFLD: a comprehensive analysis of the literature. Antioxidants. 2020 Dec;9(12):1283. https://doi.org/10.3390/antiox9121283. Go to original source... Go to PubMed...
  14. Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacology & therapeutics. 2014 Feb 1;141(2):150-159. https://doi.org/10.1016/j.pharmthera.2013.09.006. Go to original source... Go to PubMed...
  15. Samuni Y, Goldstein S, Dean OM, et al. The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013 Aug 1;1830(8):4117-4129. https://doi.org/10.1016/j.bbagen.2013.04.016 Go to original source... Go to PubMed...
  16. Kaga AK, Barbanera PO, Carmo NO, et al. Effect of N-acetylcysteine on dyslipidemia and carbohydrate metabolism in STZ-induced diabetic rats. International journal of vascular medicine. 2018 Jan 28;2018. https://doi.org/10.1155/2018/6428630. Go to original source... Go to PubMed...
  17. Di Luccia B, Crescenzo R, Mazzoli A, et al. Rescue of fructose-induced metabolic syndrome by antibiotics or faecal transplantation in a rat model of obesity. PLoS One. 2015 Aug 5;10(8):e0134893. https://doi.org/10.1371/journal.pone.0134893. Go to original source... Go to PubMed...
  18. Crescenzo R, Bianco F, Coppola P, et al. Adipose tissue remodeling in rats exhibiting fructose-induced obesity. European journal of nutrition. 2014 Mar;53(2):413-419. https://doi.org/10.1007/s00394-013-0538-2. Go to original source... Go to PubMed...
  19. Breitbart R, Abu-Kishk I, Kozer E, et al. Intraperitoneal N-acetylcysteine for acute iron intoxication in rats. Drug and Chemical Toxicology. 2011 Oct 1;34(4):429-432. https://doi.org/10.3109/01480545.2011.564176. Go to original source... Go to PubMed...
  20. Hanci V, Kerimoğlu A, Koca K, et al. The biochemical effectiveness of N-acetylcysteine in experimental spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg. 2010 Jan 1;16(1):15-21. Go to PubMed...
  21. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. Journal of pharmacology & pharmacotherapeutics. 2010 Jul;1(2):87. https://doi.org/10.4103%2F0976-500X.72350. Go to original source... Go to PubMed...
  22. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 1972 Jun 1;18(6):499-502. https://doi.org/10.1093/clinchem/18.6.499. Go to original source... Go to PubMed...
  23. Niroumand S, Khajedaluee M, Khadem-Rezaiyan M, et al. Atherogenic Index of Plasma (AIP): A marker of cardiovascular disease. Medical journal of the Islamic Republic of Iran. 2015;29:240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715400. Go to PubMed...
  24. Li JM, Wang W, Fan CY, et al. Quercetin preserves β-cell mass and function in fructose-induced hyperinsulinemia through modulating pancreatic Akt/FoxO1 activation. Evidence-Based Complementary and Alternative Medicine. 2013 Jan 1;2013. https://doi.org/10.1155/2013/303902. Go to original source... Go to PubMed...
  25. Jegatheesan P, De Bandt JP. Fructose and NAFLD: the multifaceted aspects of fructose metabolism. Nutrients. 2017 Mar;9(3):230. https://doi.org/10.3390/nu9030230. Go to original source... Go to PubMed...
  26. Smith GI, Shankaran M, Yoshino M, et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. The Journal of clinical investigation. 2020 Mar 2;130(3):1453-60. https://doi.org/10.1172/JCI134165. Go to original source...
  27. Pei Y, Liu H, Yang Y, et al. Biological activities and potential oral applications of N-acetylcysteine: progress and prospects. Oxidative medicine and cellular longevity. 2018 Apr 22;2018. https://doi.org/10.1155/2018/2835787. Go to original source... Go to PubMed...
  28. Aldini G, Altomare A, Baron G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free radical research. 2018 Jul 3;52(7):751-762. https://doi.org/10.1080/10715762.2018.1468564. Go to original source... Go to PubMed...
  29. Tardiolo G, Bramanti P, Mazzon E. Overview on the effects of N-acetylcysteine in neurodegenerative diseases. Molecules. 2018 Dec 13;23(12):3305.https://doi.org/10.3390/molecules23123305. Go to original source... Go to PubMed...
  30. Palacio JR, Markert UR, Martínez P. Anti-inflammatory properties of N-acetylcysteine on lipopolysaccharide-activated macrophages. Inflammation research. 2011 Jul;60(7):695-704.https://doi.org/10.1007/s00011-011-0323-8. Go to original source... Go to PubMed...
  31. Falach-Malik A, Rozenfeld H, Chetboun M, et al. N-Acetyl-L-Cysteine inhibits the development of glucose intolerance and hepatic steatosis in diabetes-prone mice. American journal of translational research. 2016;8(9):3744. https://api.semanticscholar.org/CorpusID:10663049. Go to PubMed...
  32. Tappy L. Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs. Clinical Nutrition. 2021 Apr 1;40(4):1691-1698. https://doi.org/10.1016/j.clnu.2020.12.022. Go to original source... Go to PubMed...
  33. Aydin S, Aksoy A, Aydin S, et al. Today's and yesterday's of pathophysiology: biochemistry of metabolic syndrome and animal models. Nutrition. 2014 Jan 1;30(1):1-9. https://doi.org/10.1016/j.nut.2013.05.013. Go to original source... Go to PubMed...
  34. Carvalho CT, de Souza MZ, Arbex N, et al. The Role of Fructose in Public Health and Obesity. Health. 2018 Apr 8;10(4):434-441. https://doi.org/10.4236/health.2018.104035. Go to original source...
  35. Ivanova EA, Myasoedova VA, Melnichenko AA, et al. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxidative medicine and cellular longevity. 2017 Oct;2017. https://doi.org/10.1155/2017/1273042. Go to original source... Go to PubMed...
  36. Haile K, Haile A, Timerga A. Predictors of Lipid Profile Abnormalities Among Patients with Metabolic Syndrome in Southwest Ethiopia: A Cross-Sectional Study. Vascular Health and Risk Management. 2021;17:461. https://doi.org/10.2147/VHRM.S319161. Go to original source... Go to PubMed...
  37. Hang W, Shu H, Wen Z, et al. N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function. Frontiers in Pharmacology. 2021;12. https://doi.org/10.3389%2Ffphar.2021.636204. Go to original source...
  38. Almeida DA, Braga CP, Novelli EL, et al. Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin. Brazilian Archives of Biology and Technology. 2012;55:527-536. https://doi.org/10.1590/S1516-89132012000400007. Go to original source...
  39. Ayyasamy R, Leelavinothan P. Myrtenal alleviates hyperglycaemia, hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats. Pharmaceutical biology. 2016 Nov 1;54(11):2521-2527. https://doi.org/10.3109/13880209.2016.1168852. Go to original source... Go to PubMed...
  40. Yang R, Le G, Li A, et al. Effect of antioxidant capacity on blood lipid metabolism and lipoprotein lipase activity of rats fed a high-fat diet. Nutrition. 2006 Nov 1;22(11-12):1185-1191. https://doi.org/10.1016/j.nut.2006.08.018. Go to original source... Go to PubMed...
  41. Zalewska A, Szarmach I, ¯endzian-Piotrowska M, et al. The effect of N-acetylcysteine on respiratory enzymes, ADP/ATP ratio, glutathione metabolism, and nitrosative stress in the salivary gland mitochondria of insulin resistant rats. Nutrients. 2020 Feb;12(2):458. https://doi.org/10.3390/nu12020458. Go to original source... Go to PubMed...
  42. Mazzoli A, Spagnuolo MS, Nazzaro M, et al. Fructose removal from the diet reverses inflammation, mitochondrial dysfunction, and oxidative stress in hippocampus. Antioxidants. 2021 Mar;10(3):487. https://doi.org/10.3390/antiox10030487. Go to original source... Go to PubMed...
  43. Twarog JP, Peraj E, Vaknin OS, et al. Consumption of sugar-sweetened beverages and obesity in SNAP-eligible children and adolescents. Primary Care Diabetes. 2020 Apr 1;14(2):181-185. https://doi.org/10.1016/j.pcd.2019.07.003. Go to original source... Go to PubMed...
  44. Miller C, Ettridge K, Wakefield M, et al. Consumption of sugar-sweetened beverages, juice, artificially-sweetened soda and bottled water: An Australian population study. Nutrients. 2020 Mar 19;12(3):817. https://doi.org/10.3390/nu12030817. Go to original source... Go to PubMed...
  45. Schulze MB, Manson JE, Ludwig DS, et al. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Jama. 2004 Aug 25;292(8):927-934. https://doi.org/10.1001/jama.292.8.927. Go to original source... Go to PubMed...
  46. Coronati M, Baratta F, Pastori D, et al. Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review. Nutrients. 2022 Mar 8;14(6):1127. https://doi.org/10.3390/nu14061127. Crujeiras AB, Carreira MC, Cabia B, et al. Leptin resistance in obesity: an epigenetic landscape. Life sciences. 2015 Nov 1;140:57-63. https://doi.org/10.1016/j.lfs.2015.05.003. Go to original source... Go to PubMed...
  47. Bawden SJ, Stephenson MC, Ciampi E, et al. Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A 31P MRS study. Clinical nutrition. 2016 Jun 1;35(3):645-649. https://doi.org/10.1016/j.clnu.2015.04.001. Go to original source... Go to PubMed...
  48. Kadota Y, Toriuchi Y, Aki Y, et al. Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway. PloS one. 2017 Apr 20;12(4):e0176070. https://doi.org/10.1371/journal.pone.0176070. Go to original source... Go to PubMed...
  49. Ma Y, Gao M, Liu D. N-acetylcysteine protects mice from high fat diet-induced metabolic disorders. Pharmaceutical research. 2016 Aug;33(8):2033-2042. https://link.springer.com/article/10.1007/s11095-016-1941-1#citeas. Go to original source... Go to PubMed...
  50. Shen FC, Weng SW, Tsao CF, et al. Early intervention of N-acetylcysteine better improves insulin resistance in diet-induced obesity mice. Free radical research. 2018 Dec 2;52(11-12):1296-310. https://doi.org/10.1080/10715762.2018.1447670. Go to original source... Go to PubMed...