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Chitosan reduces inflammation and protects against oxidative stress in a hyperlipidemic rat model: relevance to nonalcoholic fatty liver disease

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Abstract

Background

An altered lipid profile may lead to the development of inflammation and NAFLD (Non-alcoholic fatty liver disease). Although statins have a positive effect on blood lipid levels their long-term use is known to cause adverse effects, in this backdrop there is an interest in natural compounds which may affect lipid metabolism and prevent NAFLD. We have examined the effect of Chitosan on rats subjected to a high-fat diet.

Methods and results

Male Wistar middle aged rats (12–16 months) were treated with high-fat diet orally for two months for creating a NAFLD model. Rats were also supplemented with Chitosan (2% chitosan daily) for 2 months. We assessed the activity of antioxidant enzymes, the histopathological profile of the liver. Inflammatory cytokines and adiponectin levels were also measured in serum. HFD induced significant changes in liver tissue and inflammatory markers (Il-6, TNF- alpha, NF-KB). Chitosan treatment protected rats from HFD induced alterations.

Conclusions

The findings suggest that Chitosan can effectively improve liver lipid metabolism by normalizing cholesterol, triglyceride, lowering NF-KB expression, and protecting the liver from oxidative stress by improving hepatic function. Chitosan also regulates genes related to lipidemic stress i,e leptin and adiponectin.

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References

  1. Younossi ZM, Koenig AB, Abdelatif D et al (2016) Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64:73–84. https://doi.org/10.1002/hep.28431

    Article  PubMed  Google Scholar 

  2. Chalasani N, Younossi Z, Lavine JE et al (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67:328–357. https://doi.org/10.1002/hep.29367

    Article  PubMed  Google Scholar 

  3. Pydyn N, Miękus K, Jura J, Kotlinowski J (2020) New therapeutic strategies in nonalcoholic fatty liver disease: a focus on promising drugs for nonalcoholic steatohepatitis. Pharmacol Rep 72:1–12. https://doi.org/10.1007/s43440-019-00020-1

    Article  CAS  PubMed  Google Scholar 

  4. Benedict M, Zhang X (2017) Non-alcoholic fatty liver disease: an expanded review. World J Hepatol 9:715–732. https://doi.org/10.4254/wjh.v9.i16.715

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fabbrini E, Sullivan S, Klein S (2010) Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology 51:679–689. https://doi.org/10.1002/hep.23280

    Article  CAS  PubMed  Google Scholar 

  6. Fon Tacer K, Rozman D (2011) Nonalcoholic fatty liver disease: focus on lipoprotein and lipid deregulation. J Lipids 2011:1–14. https://doi.org/10.1155/2011/783976

    Article  CAS  Google Scholar 

  7. Ward NC, Watts GF, Eckel RH (2019) Statin toxicity. Circ Res 124:328–350. https://doi.org/10.1161/CIRCRESAHA.118.312782

    Article  CAS  PubMed  Google Scholar 

  8. Yan T, Yan N, Wang P et al (2020) Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharm Sin B 10:3–18. https://doi.org/10.1016/j.apsb.2019.11.017

    Article  CAS  PubMed  Google Scholar 

  9. Chen J-K, Shen C-R, Liu C-L (2010) N-Acetylglucosamine: production and applications. Mar Drugs 8:2493–2516. https://doi.org/10.3390/md8092493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kumar R, Kumar M, Rizvi SI (2021) Chitosan displays a potent caloric restriction mimetic effect in senescent rats. Rejuvenation Res. https://doi.org/10.1089/rej.2021.0010

    Article  PubMed  Google Scholar 

  11. Chiu C-Y, Yen T-E, Liu S-H, Chiang M-T (2019) Comparative effects and mechanisms of chitosan and its derivatives on hypercholesterolemia in high-fat diet-fed rats. IJMS 21:92. https://doi.org/10.3390/ijms21010092

    Article  CAS  PubMed Central  Google Scholar 

  12. Ugbaja RN, Akinloye DI, James AS et al (2020) Crab derived dietary chitosan mollifies hyperlipidemia-induced oxidative stress and histopathological derangements in male albino rats. Obes Med 20:100300. https://doi.org/10.1016/j.obmed.2020.100300

    Article  Google Scholar 

  13. Kumar R, Akhtar F, Rizvi SI (2019) Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidemic model of rat. Clin Exp Pharmacol Physiol. https://doi.org/10.1111/1440-1681.13221

    Article  PubMed  Google Scholar 

  14. Sengupta P (2013) The laboratory rat: relating its age with human’s. Int J Prev Med 4:624–630

    PubMed  PubMed Central  Google Scholar 

  15. Kumar R, Kumar M, Rizvi SI (2021) Chitosan displays a potent caloric restriction mimetic effect in senescent rats. Rejuvenation Res 24:390–396. https://doi.org/10.1089/rej.2021.0010

    Article  CAS  PubMed  Google Scholar 

  16. Agoston DV (2017) How to translate time? The temporal aspect of human and rodent biology. Front Neurol. https://doi.org/10.3389/fneur.2017.00092

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nabavi SM, Nabavi SF, Eslami S, Moghaddam AH (2012) In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue. Food Chem 132:931–935. https://doi.org/10.1016/j.foodchem.2011.11.070

    Article  CAS  Google Scholar 

  18. Tripathi SS, Singh S, Garg G et al (2019) Metformin ameliorates acetaminophen-induced sub-acute toxicity via antioxidant property. Drug Chem Toxicol. https://doi.org/10.1080/01480545.2019.1658769

    Article  PubMed  Google Scholar 

  19. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    Article  CAS  Google Scholar 

  20. Aebi H, Wyss SR, Scherz B, Skvaril F (1974) Heterogeneity of erythrocyte catalase II. Isolation and characterization of normal and variant erythrocyte catalase and their subunits. Eur J Biochem 48:137–145. https://doi.org/10.1111/j.1432-1033.1974.tb03751.x

    Article  CAS  PubMed  Google Scholar 

  21. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    Article  CAS  Google Scholar 

  22. Nelson RH (2013) Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 40:195–211. https://doi.org/10.1016/j.pop.2012.11.003

    Article  PubMed  Google Scholar 

  23. Paschos P, Paletas K (2009) Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia 13:9–19

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Alves-Bezerra M, Cohen DE (2017) Triglyceride metabolism in the liver. Compr Physiol 8:1–8. https://doi.org/10.1002/cphy.c170012

    Article  PubMed  PubMed Central  Google Scholar 

  25. Silva Figueiredo P, Carla Inada A, Marcelino G et al (2017) Fatty acids consumption: the role metabolic aspects involved in obesity and its associated disorders. Nutrients 9:1158. https://doi.org/10.3390/nu9101158

    Article  CAS  PubMed Central  Google Scholar 

  26. Marra F, Lotersztajn S (2013) Pathophysiology of NASH: perspectives for a targeted treatment. CPD 19:5250–5269. https://doi.org/10.2174/13816128113199990344

    Article  CAS  Google Scholar 

  27. Wang K (2014) Molecular mechanisms of hepatic apoptosis. Cell Death Dis 5:e996–e996. https://doi.org/10.1038/cddis.2013.499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Robeva R, Mladenović D, Vesković M et al (2021) The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause. Maturitas 151:22–30. https://doi.org/10.1016/j.maturitas.2021.06.012

    Article  CAS  PubMed  Google Scholar 

  29. Venetsanaki V, Polyzos SA (2019) Menopause and non-alcoholic fatty liver disease: a review focusing on therapeutic perspectives. CVP 17:546–555. https://doi.org/10.2174/1570161116666180711121949

    Article  CAS  Google Scholar 

  30. Sofowora A, Ogunbodede E, Onayade A (2013) The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med 10:210–229. https://doi.org/10.4314/ajtcam.v10i5.2

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ye J, DeBose-Boyd RA (2011) Regulation of cholesterol and fatty acid synthesis. Cold Spring Harb Perspect Biol 3:a004754. https://doi.org/10.1101/cshperspect.a004754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131. https://doi.org/10.1172/JCI0215593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shao W, Espenshade PJ (2021) Lipids | Cholesterol synthesis and regulation. In: Encyclopedia of biological chemistry III. Elsevier, pp 732–738

  34. Yang D, Hu C, Deng X et al (2019) Therapeutic effect of chitooligosaccharide tablets on lipids in high-fat diets induced hyperlipidemic rats. Molecules 24:514. https://doi.org/10.3390/molecules24030514

    Article  CAS  PubMed Central  Google Scholar 

  35. Liu S-H, Chen R-Y, Chiang M-T (2021) Effects and mechanisms of chitosan and chitosanoligosaccharide on hepatic lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in rats with high-fat diet-induced obesity. IJMS 22:1139. https://doi.org/10.3390/ijms22031139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nowak WN, Deng J, Ruan XZ, Xu Q (2017) Reactive oxygen species generation and atherosclerosis. ATVB. https://doi.org/10.1161/ATVBAHA.117.309228

    Article  Google Scholar 

  37. Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950. https://doi.org/10.1152/physrev.00026.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li S, Tan H-Y, Wang N et al (2015) The role of oxidative stress and antioxidants in liver diseases. IJMS 16:26087–26124. https://doi.org/10.3390/ijms161125942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tangvarasittichai S (2015) Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. WJD 6:456. https://doi.org/10.4239/wjd.v6.i3.456

    Article  PubMed  PubMed Central  Google Scholar 

  40. Csonka C, Baranyai T, Tiszlavicz L et al (2017) Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas. Lipids Health Dis 16:144. https://doi.org/10.1186/s12944-017-0537-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Feingold KR, Grunfeld C (1992) Role of cytokines in inducing hyperlipidemia. Diabetes 41:97–101. https://doi.org/10.2337/diab.41.2.S97

    Article  CAS  PubMed  Google Scholar 

  42. Chen Z, Tian R, She Z et al (2020) Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med 152:116–141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025

    Article  CAS  PubMed  Google Scholar 

  43. Ouchi N, Walsh K (2007) Adiponectin as an anti-inflammatory factor. Clin Chim Acta 380:24–30. https://doi.org/10.1016/j.cca.2007.01.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Berg AH, Scherer PE (2005) Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96:939–949. https://doi.org/10.1161/01.RES.0000163635.62927.34

    Article  CAS  PubMed  Google Scholar 

  45. Guan G, Azad MdAK, Lin Y et al (2019) Biological effects and applications of chitosan and chito-oligosaccharides. Front Physiol 10:516. https://doi.org/10.3389/fphys.2019.00516

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 152:93–100. https://doi.org/10.7326/0003-4819-152-2-201001190-00008

    Article  PubMed  PubMed Central  Google Scholar 

  47. Park H-K, Ahima RS (2015) Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism 64:24–34. https://doi.org/10.1016/j.metabol.2014.08.004

    Article  CAS  PubMed  Google Scholar 

  48. Izquierdo AG, Crujeiras AB, Casanueva FF, Carreira MC (2019) Leptin, obesity, and leptin resistance: where are we 25 years later? Nutrients 11:2704. https://doi.org/10.3390/nu11112704

    Article  CAS  PubMed Central  Google Scholar 

  49. Ostlund RE, Yang JW, Klein S, Gingerich R (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 81:3909–3913. https://doi.org/10.1210/jcem.81.11.8923837

    Article  CAS  PubMed  Google Scholar 

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Funding

The Department of Biotechnology, Government of India, has provided financial support under the ‘Research Resources, Service Facilities, and Platforms’ program. The Department of Biochemistry is funded by the DST, FIST Grant, New Delhi, and the SAP DRS I from UGC.

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Authors and Affiliations

  1. Department of Biochemistry, University of Allahabad, Allahabad, 211002, India

    Raushan Kumar, Jitendra Kumar Arya & Syed Ibrahim Rizvi

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  1. Raushan Kumar
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  2. Jitendra Kumar Arya
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Contributions

RK Performing experiments, compiling results, a draft of the manuscript. JKA Performing experiments. SIR Conception of the study, analysis of results, and manuscript preparation.

Corresponding author

Correspondence to Syed Ibrahim Rizvi.

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The authors of this manuscript have no conflict of interest.

Ethical approval

The study was carried out by the guideline given by the U.S. Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Guide) as well as protocol approval approved by the Ethical Committee of the University of Allahabad, Allahabad.

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Kumar, R., Arya, J.K. & Rizvi, S.I. Chitosan reduces inflammation and protects against oxidative stress in a hyperlipidemic rat model: relevance to nonalcoholic fatty liver disease. Mol Biol Rep 49, 9465–9472 (2022). https://doi.org/10.1007/s11033-022-07810-6

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