A modified high-fat diet and its effect on histopathological features of mice liver as an alternative diet for animal model of liver cell damage

  • Dzul Fithria Mumtazah Biology Department, FMIPA Unila
  • Hendri Busman Biology Department, FMIPA Unila
  • Mohammad Kanedi Biology Department, FMIPA Unila
  • Gina Dania Pratami Biology Department, FMIPA Unila


Researchers attempted to obtain animal models that experienced hypercholesterolemia and led to liver damage to determine the performance of the liver. Rats were chosen because of the ease of handling, collecting organ and blood samples. Still, their high price and availability that are more difficult to find have made some researchers look for alternatives to other animal models such as mice. This study aims to determine the role of a modified high-fat diet as an alternative diet for mice to experience hepar damage. Male mice treated for four and eight weeks with a modified high-fat diet were sacrificed for their liver, then they were tested for histopathology using the paraffin method and HE staining. The characterization of hepar damage traits was carried out to score the degree of parenchymal degeneration, hydropic degeneration, and necrosis. The results showed that the control group, four and eight weeks of atherogenic diet had more than 50% cell damage, presumably due to the role of the starch mixture in feed as a source of carbohydrates through the mechanism of converting carbohydrate pathways into fat which damages liver cells.


Abdelhalim MAK, Jarrar BM. 2011. Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver. Lipids in Health and Disease. vol 10(1): 1–6. doi: https://doi.org/10.1186/1476-511X-10-166.

Abdelzaher OF, Abdoon AS, Rady MI, Abd-Elgalil MM, Mehany AB, Mohammed FE. 2018. Hepatic and renal histopathological and ultrastructural alterations following exposure to different gold nanoparticle sizes in female pregnant rats. Al-Azhar Bulletin of Science. vol 29(2): 25–38. doi: https://dx.doi.org/10.21608/absb.2018.33816.

Adiwinata R, Kristanto A, Christianty F, Richard T, Edbert D. 2015. Tatalaksana terkini perlemakan hati non alkoholik. Jurnal Penyakit Dalam Indonesia. vol 2(1): 53–59. doi: http://dx.doi.org/10.7454/jpdi.v2i1.65.

Al-Griw MA, Alghazeer RO, Al-Azreg SA, Bennour EM. 2016. Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality. Open Veterinary Journal. vol 6(3): 150–157. doi: https://doi.org/10.4314/ovj.v6i3.1.

Asuzu IM, Ugwa E, Ezike KN. 2019. Hydropic degeneration of uterine leiomyoma mimicking a huge ovarian cyst. International Journal of Case Reports and Images. vol 10: 1-6. doi: https://doi.org/10.5348/101002Z01IA2019CR.

Basaranoglu M, Basaranoglu G, Bugianesi E. 2015. Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction. Hepatobiliary Surgery and Nutrition. vol 4(2): 109–116. doi: https://dx.doi.org/10.3978%2Fj.issn.2304-3881.2014.11.05.

Bhupathiraju SN, Tucker KL. 2011. Coronary heart disease prevention: nutrients, foods, and dietary patterns. Clinica Chimica Acta. vol 412(17-18): 1493–1514. doi: https://doi.org/10.1016/j.cca.2011.04.038.

Bryda EC. 2013. The mighty mouse: the impact of rodents on advances in biomedical research. Missouri Medicine. vol (3): 207–211.

Byrne CD, Targher G. 2015. NAFLD: a multisystem disease. Journal of Hepatology. vol 62(1): 47–64. doi: https://doi.org/10.1016/j.jhep.2014.12.012.

Freitas SH, Dória RGS, Bueno RS, Rocha WB, Filho JRE, Moraes JRE, Vidane AS, Ambrósio CE. 2017. Evaluation of potential changes in liver and lung tissue of rats in an ischemia-reperfusion injury model (modified pringle maneuver). PLoS One. vol 12(6): 1–13. doi: https://doi.org/10.1371/journal.pone.0178665.

Gao X, Yu B, Yu J, Mao X, Huang Z, Luo Y, Luo J, Zheng P, He J, Chen D. 2020. Effects of dietary starch structure on growth performance, serum glucose–insulin response, and intestinal health in weaned piglets. Animals. vol 10(3): 1–15. doi: https://doi.org/10.3390/ani10030543.

Gargiulo S, Gramanzini M, Megna R, Greco A, Albanese S, Manfredi C, Brunetti A. 2014. Evaluation of growth patterns and body composition in C57Bl/6J mice using dual energy X-ray absorptiometry. BioMed Research International. vol 2014: 1–12. doi: https://doi.org/10.1155/2014/253067.

Geng Y, Faber KN, de Meijer VE, Blokzijl H, Moshage H. 2021. How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?. Hepatology International. vol 15: 21–35. doi: https://doi.org/10.1007/s12072-020-10121-2.

Gissen P, Arias IM. 2015. Structural and functional hepatocyte polarity and liver disease. Journal of Hepatology. vol 3(4): 1023–1037. doi: https://doi.org/10.1016/j.jhep.2015.06.015.

Hawkins P, Armstrong R, Boden T, Garside P, Knight K, Lilley E, Seed M, Wilkinson M, Williams RO. 2015. Applying refinement to the use of mice and rats in rheumatoid arthritis research. Inflammopharmacology. vol 23(4): 131–150. doi: https://doi.org/10.1007/s10787-015-0241-4.

Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. 2017. Commonly used animal models. In Principles of animal research for graduate and undergraduate students. New York: Elsevier Inc. pp 117–175. doi: https://dx.doi.org/10.1016%2FB978-0-12-802151-4.00007-4.

Jarrar BM, Taib NT. 2012. Histological and histochemical alterations in the liver induced by lead chronic toxicity. Saudi Journal of Biological Sciences. vol 19(2): 203–210. doi: https://doi.org/10.1016/j.sjbs.2011.12.005.

Kementerian Kesehatan. 2021. Penyakit jantung koroner didominasi masyarakat Kota. Jakarta: Kementerian Kesehatan Republik Indonesia. https://www.kemkes.go.id/.

Lee KY, Yoo SH, Lee HG. 2012. The effect of chemically‐modified resistant starch, RS type‐4, on body weight and blood lipid profiles of high fat diet‐induced obese mice. Starch‐Stärke. vol 64(1): 78–85. doi: https://doi.org/10.1002/star.201100057.

Li L, Mo F, Hui EP, Chan SL, Koh J, Tang NLS, Yu SCH, Yeo W. 2019. The association of liver function and quality of life of patients with liver cancer. BMC Gastroenterology. vol 19: 1–12. doi: https://doi.org/10.1186/s12876-019-0984-2.

Lind L, Simon T, Johansson L, Kotti S, Hansen T, Machecourt J, Ninio E, Tedgui A, Danchin N, Ahlström H, Mallat Z. 2012. Circulating levels of secretory-and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality. European Heart Journal. vol 33(23): 2946–2954. doi: https://doi.org/10.1093/eurheartj/ehs132.

Maurice J, Manousou P. 2018. Non-alcoholic fatty liver disease. Clinical Medicine. vol 18(3): 245–250. doi: https://dx.doi.org/10.7861%2Fclinmedicine.18-3-245.

Murakami M, Yamamoto K, Miki Y, Murase R, Sato H, Taketomi Y. 2016. The roles of the secreted phospholipase A2 gene family in immunology. Advances in Immunology. vol 132: 91–134. doi: https://doi.org/10.1016/bs.ai.2016.05.001.

Murase R, Sato H, Yamamoto K, Ushida A, Nishito Y, Ikeda K, Kobayashi T, Yamamoto T, Taketomi Y, Murakami M. 2016. Group X secreted phospholipase A2 releases ω3 polyunsaturated fatty acids, suppresses colitis, and promotes sperm fertility. Journal of Biological Chemistry. vol 291(13): 6895–6911. doi: https://doi.org/10.1074/jbc.M116.715672.

Murwani S, Ali M, Muliartha K. 2013. Diet aterogenik pada tikus putih (Rattus novergicus strain Wistar) sebagai model hewan aterosklerosis. Jurnal Kedokteran Brawijaya. vol 22(1): 6–9. doi: http://dx.doi.org/10.21776/ub.jkb.2006.022.01.2.

Panqueva RDPL. 2013. Hepatopathology for gastroenterologists and hepatologists. Part two: Useful terminology in the interpretation of the histopathological findings. Revista Colombiana de Gastroenterologia. vol 28(3): 247–255.

Poston RN. 2019. Atherosclerosis: integration of its pathogenesis as a self-perpetuating propagating inflammation: a review. Cardiovascular Endocrinology & Metabolism. vol 8(2): 51–61. doi: https://dx.doi.org/10.1097%2FXCE.0000000000000172.

Rahardjo T, Nurhayati S, Ramadhani D. 2013. Liver histophatological studies of mice (Mus musculus sp.) infected with gamma rays irradiated Plasmodium berghei strains Anka. HAYATI Journal of Biosciences. vol 20(3): 144–150. doi: https://doi.org/10.4308/hjb.20.3.144.

Ramos CAF, Sá RDCDS, Alves MF, Benedito RB, de Sousa DP, Diniz MDFFM, Araújo MST, de Almeida RN. 2015. Histopathological and biochemical assessment of d-limonene-induced liver injury in rats. Toxicology Reports. vol 2: 482–488. doi: https://doi.org/10.1016/j.toxrep.2015.01.001.

Rosenson RS, Hurt-Camejo E. 2012. Phospholipase A2 enzymes and the risk of atherosclerosis. European Heart Journal. vol 33(23): 2899–2909. doi: https://doi.org/10.1093/eurheartj/ehs148.

Ruan P, Yang C, Su J, Cao J, Ou C, Luo C, Tang Y, Wang Q, Yang F, Shi J, Lu X, Zhu L, Qin H, Sun W, Lao Y, Li Y. 2013. Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus. Virology Journal. vol 10: 1–11. doi: https://doi.org/10.1186/1743-422X-10-333.

Santoso A, Heriansyah T, Rohman MS. 2020. Phospholipase A2 is an inflammatory predictor in cardiovascular diseases: is there any spacious room to prove the causation?. Current Cardiology Reviews. vol 16(1): 3–10. doi: https://doi.org/10.2174/1573403X15666190531111932.

Schulze RJ, Schott MB, Casey CA, Tuma PL, McNiven MA. 2019. The cell biology of the hepatocyte: A membrane trafficking machine. Journal of Cell Biology. vol 218(7): 2096–2112. doi: https://doi.org/10.1083/jcb.201903090.

Stanek M, Rotkiewicz T, Sobotka W, Bogusz J, Otrocka-Domagała I, Rotkiewicz A. 2015. The effect of alkaloids present in blue lupine (Lupinus angustifolius) seeds on the growth rate, selected biochemical blood indicators and histopathological changes in the liver of rats. Acta Veterinaria Brno. vol 84(1): 55–62. doi: https://doi.org/10.2754/avb201585010055.

Szpirer C. 2020. Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes. Journal of Biomedical Science. vol 27(1): 1–52. doi: https://doi.org/10.1186/s12929-020-00673-8.

Wang L, Wang Y, Liang Y, Li J, Liu Y, Zhang J, Zhang A, Fu J, Jiang G. 2013. Specific accumulation of lipid droplets in hepatocyte nuclei of PFOA-exposed BALB/c mice. Scientific Reports. vol 3(1): 1–5. doi: https://doi.org/10.1038/srep02174.

Zheng J, Ji C, Lu X, Tong W, Fan X, Gao Y. 2015. Integrated expression profiles of mRNA and microRNA in the liver of Fructus Meliae Toosendan water extract injured mice. Frontiers in Pharmacology. vol 6: 1–13. doi: https://doi.org/10.3389/fphar.2015.00236.

Zheng B, Wang T, Wang H, Chen L, Zhou Z. 2020. Studies on nutritional intervention of rice starch-oleic acid complex (resistant starch type V) in rats fed by high-fat diet. Carbohydrate Polymers. vol 246: 1–35. doi: https://doi.org/10.1016/j.carbpol.2020.116637.

Zhou Z, Xu MJ, Gao B. 2016. Hepatocytes: a key cell type for innate immunity. Cellular & Molecular Immunology. vol 13(3): 301–315. doi: https://doi.org/10.1038/cmi.2015.97.

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