Effects of probiotics and high fructose diet on De Ritis ratio, TGF-B levels, and liver histopathology of Sprague Dawley rats

Ninung Rose Diana Kusumawati; Damianus Galih Panunggal; Maria Mexitelia; Magdalena Sidhartani; Agustini Utari

doi:10.15562/bmj.v11i3.3397

Effects of probiotics and high fructose diet on De Ritis ratio, TGF-B levels, and liver histopathology of Sprague Dawley rats

Ninung Rose Diana Kusumawati ,

Damianus Galih Panunggal ,

Maria Mexitelia ,

Magdalena Sidhartani ,

Agustini Utari ,

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DOI: https://doi.org/10.15562/bmj.v11i3.3397 |
Published: 2022-09-05

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Histopathological diagnosis has been the gold standard for diagnosing and determining the severity of non-alcoholic steatohepatitis (NASH). However, this method is invasive, especially for diagnosing NASH in children. This research aimed to study the effect of probiotics on the De Ritis ratio, TGF-β levels, and histopathological changes in rats given High Fat, High Fructose (HFHFr) diet to look at the correlation between the De Ritis ratio and liver histopathology in diagnosing NAFLD.

Method: Twenty-one male Sprague Dawley rats were included and divided into three groups. In the first group, as control only received a normal chow diet for eight weeks. The second group received an HFHFr diet for eight weeks, and the last group received HFHFr for eight weeks and a combination of HFHFr and probiotics for another eight weeks. After decapitation, we took 3 ml of serum from each rat to measure AST, ALT, and TGF-β. A 4 μm thick liver tissue slide was taken and stained with Hematoxylin – Eosin Stain for histopathological analysis. We used the Non-Alcoholic Steatohepatitis (NAS) Score for measuring liver damage progression.

Results: De Ritis ratio and TGF-β level did not significantly differ between probiotic and non-probiotic groups (p = 0.064 and 0.383), but there was a significant NAS score difference (p = 0.001) in probiotic and non-probiotic groups. This was followed by a significant correlation between the De Ritis ratio and the NAS score (r = 0.613, p = 0.003).

Conclusion: Probiotic supplementation alleviated liver damage caused by the HFHFr diet but did not successfully reduce the De Ritis ratio or improve TGF-β.

References

REFERENCES
Younossi Z, Tacke F, Arrese M, et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. 2019;69(6):2672-2682. doi:10.1002/hep.30251.
Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-S64. doi:10.1016/j.jhep.2014.12.012.
Flisiak-Jackiewicz M, Lebensztejn DM. Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children. Clin Exp Hepatol. 2019;5(1):11-21. doi:10.5114/ceh.2019.83152.
Mouries J, Brescia P, Silvestri A, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019;71(6):1216-1228. doi:10.1016/j.jhep.2019.08.005.
Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019;76(8):1541-1558. doi:10.1007/s00018-019-03011-w.
Henao-Mejia J, Elinav E, Jin C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179-185. Published 2012 Feb 1. doi:10.1038/nature10809.
Jiang X, Zheng J, Zhang S, Wang B, Wu C, Guo X. Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD. Front Med (Lausanne). 2020;7:361. Published 2020 Jul 29. doi:10.3389/fmed.2020.00361.
Sarwar R, Pierce N, Koppe S. Obesity and nonalcoholic fatty liver disease: current perspectives. Diabetes Metab Syndr Obes. 2018;11:533-542. Published 2018 Sep 25. doi:10.2147/DMSO.S146339.
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321. doi:10.1002/hep.20701.
Botros M, Sikaris KA. The de ritis ratio: the test of time. Clin Biochem Rev. 2013;34(3):117-130.
Gadallah SH, Eissa S, Ghanem HM, et al. Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model. Biomed Pharmacother. 2021;140:111781. doi:10.1016/j.biopha.2021.111781.
Mazloom K, Siddiqi I, Covasa M. Probiotics: How Effective Are They in the Fight against Obesity?. Nutrients. 2019;11(2):258. Published 2019 Jan 24. doi:10.3390/nu11020258.
Eslamparast T, Eghtesad S, Hekmatdoost A, Poustchi H. Probiotics and Nonalcoholic Fatty liver Disease. Middle East J Dig Dis. 2013;5(3):129-136.
Kanmani P, Kim H. Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of TGF-β/SMAD signaling and autophagy in hepatic stellate cells. PLoS One. 2022;17(1):e0262767. Published 2022 Jan 20. doi:10.1371/journal.pone.0262767.

[1] REFERENCES

[2] Younossi Z, Tacke F, Arrese M, et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. 2019;69(6):2672-2682. doi:10.1002/hep.30251.

[3] Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-S64. doi:10.1016/j.jhep.2014.12.012.

[4] Flisiak-Jackiewicz M, Lebensztejn DM. Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children. Clin Exp Hepatol. 2019;5(1):11-21. doi:10.5114/ceh.2019.83152.

[5] Mouries J, Brescia P, Silvestri A, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019;71(6):1216-1228. doi:10.1016/j.jhep.2019.08.005.

[6] Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019;76(8):1541-1558. doi:10.1007/s00018-019-03011-w.

[7] Henao-Mejia J, Elinav E, Jin C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179-185. Published 2012 Feb 1. doi:10.1038/nature10809.

[8] Jiang X, Zheng J, Zhang S, Wang B, Wu C, Guo X. Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD. Front Med (Lausanne). 2020;7:361. Published 2020 Jul 29. doi:10.3389/fmed.2020.00361.

[9] Sarwar R, Pierce N, Koppe S. Obesity and nonalcoholic fatty liver disease: current perspectives. Diabetes Metab Syndr Obes. 2018;11:533-542. Published 2018 Sep 25. doi:10.2147/DMSO.S146339.

[10] Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321. doi:10.1002/hep.20701.

[11] Botros M, Sikaris KA. The de ritis ratio: the test of time. Clin Biochem Rev. 2013;34(3):117-130.

[12] Gadallah SH, Eissa S, Ghanem HM, et al. Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model. Biomed Pharmacother. 2021;140:111781. doi:10.1016/j.biopha.2021.111781.

[13] Mazloom K, Siddiqi I, Covasa M. Probiotics: How Effective Are They in the Fight against Obesity?. Nutrients. 2019;11(2):258. Published 2019 Jan 24. doi:10.3390/nu11020258.

[14] Eslamparast T, Eghtesad S, Hekmatdoost A, Poustchi H. Probiotics and Nonalcoholic Fatty liver Disease. Middle East J Dig Dis. 2013;5(3):129-136.

[15] Kanmani P, Kim H. Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of TGF-β/SMAD signaling and autophagy in hepatic stellate cells. PLoS One. 2022;17(1):e0262767. Published 2022 Jan 20. doi:10.1371/journal.pone.0262767.

Effects of probiotics and high fructose diet on De Ritis ratio, TGF-B levels, and liver histopathology of Sprague Dawley rats

Abstract

References

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