Biochemical and Histopathology Analysis of Liver Damage in Hypercholesterolemic Rats Induced by Tomato Extract

Retno Sri Iswari(1), Muchamad Dafip(2), Muhammad Rifa'i(3),

DOI: https://doi.org/10.15294/biosaintifika.v12i3.23337


(1) Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Indonesia
(2) Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Indonesia
(3) Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Indonesia

Abstract

Hypercholesterolemia is a condition caused by high cholesterol consumption. Tomatoes is well known has cholesterol-lowering effects. However, high consumption of tomato shall be concerned especially prooxidant potential that may damage the organ, especially in liver. This study aims to understand the effect of hypercholesterolemic and tomato administration to the rat’s liver, which is monitored using aspartate transaminase (AST), alanine transaminase (ALT) and histological condition. A total 24 of 12-weeks-old male-rats divided into 4 groups, equally. The K1 as normal group consist of placebo-treatment rats; K2 group as hypercholesterolemia group induced with high-cholesterol diet and 2 ml of cholesterol; K3 group was hypercholesterolemia rats treated with 20 mg of atorvastatin; and the last is K4 group was cholesterol rats supplemented with 16 mg/ day of tomato extract. All samples were treated for 60 days. The highest levels of AST and ALT level was 76.39 U/L and 45.40 U/L, respectively, was found in K2. Then, K4 is not significantly different from K3 and K1 and significantly different from K2. The scoring results showed that all groups experienced damage in the form of parenchymal degeneration, fat degeneration and necrosis. From this study it can be concluded that tomato extract gives a protection to the liver from cholesterol-oxidation damage effect. The updating information about how tomato inhibite liver fattening. The liver condition probably can be considered as biomarker-related hypercholesterolemia and developed a diagnostic marker to prevent increases metabolic disorder in community.

Keywords

hypercholesterolemia; liver; tomatoes

Full Text:

PDF

References

Agmon, E., & Stockwell, B. R. (2017). Lipid ho-meostasis and regulated cell death. Current Opinion in Chemical Biology, 39, 83–89.

Antal, I., Koneracka, M., Zavisova, V., Ku-bovcikova, M., Kormosh, Z., & Kopcansky, P. (2017). Statins Determination: A Review of Electrochemical Techniques. Critical Reviews in Analytical Chemistry, 47(6), 474–489.

Barros, M. P., Rodrigo, M. J., & Zacarias, L. (2018). Dietary Carotenoid Roles in Redox Homeostasis and Human Health [Review-article]. Journal of Agricultural and Food Chemistry, 66(23), 5733–5740.

Bruder-Nascimento, T., Callera, G. E., Montezano, A. C., Belin de Chantemele, E. J., Tostes, R. C., & Touyz, R. M. (2019). Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxi-dative stress. Life Sciences, 221(February), 29–34.

Camerino, G. M., De Bellis, M., Conte, E., Lianto-nio, A., Musaraj, K., Cannone, M., Fonzino, A., Giustino, A., De Luca, A., Romano, R., Came-rino, C., Laghezza, A., Loiodice, F., Desaphy, J. F., Conte Camerino, D., & Pierno, S. (2016). Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin. Toxicolo-gy and Applied Pharmacology, 306, 36–46.

Cheng, H. M., Koutsidis, G., Lodge, J. K., Ashor, A., Siervo, M., & Lara, J. (2017). Tomato and lycopene supplementation and cardiovascular risk factors: A systematic review and meta-analysis. In Atherosclerosis (Vol. 257, Issue 3).

Choi, Y., Abdelmegeed, M. A., & Song, B. J. (2017). Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeosta-sis and increased oxidative stress. Food and Chemical Toxicology, 103, 111–121.

Clarke, A. T., Johnson, P. C. D., Hall, G. C., Ford, I., & Mills, P. R. (2016). High dose atorvastatin associated with increased risk of significant hepatotoxicity in comparison to simvastatin in UK GPRD cohort. PLoS ONE, 11(3), 1–13.

Desmarchelier, C., & Borel, P. (2017). Overview of carotenoid bioavailability determinants: From dietary factors to host genetic variations. Trends in Food Science and Technology, 69, 270–280.

Dixit, A., & Icahn, A. A. (2018). Atorvastatin-associated necrotizing autoimmune myopathy: A case report. Case Reports in Rheumatology, 82(9), 559–562.

Eghbaliferiz, S., & Iranshahi, M. (2016). Prooxi-dant Activity of Polyphenols, Flavonoids, An-thocyanins and Carotenoids: Updated Review of Mechanisms and Catalyzing Metals. Phyto-therapy Research, May, 1379–1391.

Elias, M. D. B., Oliveira, F. L., Guma, F. C. R., Martucci, R. B., Borojevic, R., & Teodoro, A. J. (2019). Lycopene inhibits hepatic stellate cell activation and modulates cellular lipid storage and signaling. Food and Function, 10(4), 1974–1984.

Fried, L. F. (2008). Effects of HMG-CoA reduc-tase inhibitors (statins) on progression of kid-ney disease. Kidney International, 74(5), 571–576.

Ghelani, H., Razmovski-Naumovski, V., Chang, D., & Nammi, S. (2019). Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats. BMC Nephrology, 20(1).

Ghosh, N., Das, A., Chaffee, S., Roy, S., & Sen, C. K. (2018). Reactive Oxygen Species, Oxida-tive Damage and Cell Death. In Immunity and Inflammation in Health and Disease. Elsevier Inc.

Grosso, G., Bei, R., Mistretta, A., Marventano, S., Calabrese, G., Masuelli, L., Giganti, G., Modes-ti, A., Galvano, F., & Gazzolo, D. (2013). Ef-fects of Vitamin C on health: a review of evi-dence. Frontiers in Bioscience, 1(18), 1017–1029.

Hiebl, V., Ladurner, A., Latkolik, S., & Dirsch, V. M. (2018). Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR. Biotechnology Advances, 36(6), 1657–1698.

Iswari, R. S., & Susanti, R. (2016). Antioxidant Activity from Various Tomato Processing. Bi-osaintifika: Journal of Biology & Biology Edu-cation, 8(1), 127.

Kawata, A., Murakami, Y., Suzuki, S., & Fujisa-wa, S. (2018). Anti-inflammatory activity of β-carotene, lycopene and tri-n-butylborane, a scavenger of reactive oxygen species. In Vivo, 32(2), 255–264.

Kloska, A., Węsierska, M., Malinowska, M., Gabig-Cimińska, M., & Jakóbkiewicz-Banecka, J. (2020). Lipophagy and lipolysis status in li-pid storage and lipid metabolism diseases. In-ternational Journal of Molecular Sciences, 21(17), 1–33.

Lobo, G. P., Amengual, J., Li, H. N. M., Golczak, M., Bonet, M. L., Palczewski, K., & Von Lintig, J. (2010). Β,Β-Carotene Decreases Peroxisome Proliferator Receptor Γ Activity and Reduces Lipid Storage Capacity of Adipocytes in a Β,Β-Carotene Oxygenase 1-Dependent Manner. Journal of Biological Chemistry, 285(36), 27891–27899.

Lowe, G. M., Graham, D. L., & Young, A. J. (2018). Lycopene: Chemistry, Metabolism, and Bioavailability. In A. V. Rao, G. L. Young, & L. G. Rao (Eds.), Lycopene and Tomatoes in Human Nutrition and Health, preventing chronic diseases (pp. 1–20).

Mato, J. M., Alonso, C., Noureddin, M., & Lu, S. C. (2019). Biomarkers and subtypes of de-ranged lipid metabolism in nonalcoholic fatty liver disease. World Journal of Gastroenterolo-gy, 25(24), 3009–3020.

Matos, S. L., de Paula, H., Pedrosa, M. L., dos Santos, R. C., de Oliveira, E. L., Júnior, D. A. C., & Silva, M. E. (2005). Dietary Models for Inducing Hypercholesterolemia in Rats. Brazil-ian Archives of Biology and Technology, 48(2), 203–209.

Ooi, B. K., Goh, B. H., & Yap, W. H. (2017). Ox-idative stress in cardiovascular diseases: In-volvement of Nrf2 antioxidant redox signaling in macrophage foam cells formation. Interna-tional Journal of Molecular Sciences, 18(11).

Otunola, G. A., Oloyede, O. B., Oladiji, A. T., & Afolayan, A. A. (2010). Effects of diet-induced hypercholesterolemia on the lipid pro-file and some enzyme activities in female Wistar rats. African Journal of Biochemistry Research, 4(6), 149–154.

Pacier, C., Martirosyan, D. M., & Martirosyan, D. (2015). Vitamin C: optimal dosages, supple-mentation and use in disease prevention. Func-tional Foods in Health and Disease, 5(3), 89–107.

Ramachandran, R., & Kakar, S. (2009). Histologi-cal patterns in drug-induced liver disease. Journal of Clinical Pathology, 62(6), 481–492.

Ramakumari, N., Indumathi, B., Katkam, S. K., & Kutala, V. K. (2018). Impact of pharmaco-genetics on statin-induced myopathy in South-Indian subjects. Indian Heart Journal, 70, S120–S125.

Ramírez, C. M., Rotllan, N., Vlassov, A. V., Dáva-los, A., Li, M., Goedeke, L., Aranda, J. F., Cire-ra-Salinas, D., Araldi, E., Salerno, A., Wanschel, A., Zavadil, J., Castrillo, A., Kim, J., Suárez, Y., & Fernández-Hernando, C. (2013). Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circulation Research, 112(12), 1592–1601.

Ratneswaran, A., Sun, M. M. G., Dupuis, H., Saw-yez, C., Borradaile, N., & Beier, F. (2017). Nu-clear receptors regulate lipid metabolism and oxidative stress markers in chondrocytes. Jour-nal of Molecular Medicine, 95(4), 431–444.

Ribeiro, D., Freitas, M., Silva, A. M. S., Carvalho, F., & Fernandes, E. (2018). Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food and Chemical Toxi-cology, 120(July), 681–699.

Thies, F., Mills, L. M., Moir, S., & Masson, L. F. (2017). Cardiovascular benefits of lycopene: Fantasy or reality? Proceedings of the Nutrition Society, 76(2), 122–129.

Treml, J., & Šmejkal, K. (2016). Flavonoids as Potent Scavengers of Hydroxyl Radicals. Com-prehensive Reviews in Food Science and Food Safety, 15(4), 720–738.

Xu, P., Zhai, Y., & Wang, J. (2018). The role of PPAR and its cross-talk with CAR and LXR in obesity and atherosclerosis. International Jour-nal of Molecular Sciences, 19(4).

Zeng, H., & Liu, Z. (2019). Atorvastatin induces hepatotoxicity in diabetic rats via oxidative stress, inflammation, and anti-apoptotic path-way. Medical Science Monitor, 25, 6165–6173.

Zhao, Y., Ma, D.-X., Wang, H.-G., Li, M.-Z., Ta-lukder, M., Wang, H.-R., & Li, J.-L. (2020). Lycopene Prevents DEHP-Induced Liver Lipid Metabolism Disorder by Inhibiting the HIF-1α-Induced PPARα/PPARγ/FXR/LXR System. Journal of Agricultural and Food Chemistry, 68(41), 11468–11479.

Zheng-Hong, Q. (2019). Autophagy: biology and diseases. In Advances in Experimental Medi-cine and Biology (Vol. 1206).

Refbacks

  • There are currently no refbacks.


Bookmark and Share


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.