Sains Malaysiana 52(10)(2023): 2829-2841

http://doi.org/10.17576/jsm-2023-5210-08

Polyunsaturated Fatty Acids from Eel Extract Attenuate Gastritis and Hepatotoxic by Indomethacin-Induced in Rats

(Asid Lemak Politaktepu daripada Ekstrak Belut Melemahkan Gastritis dan Hepatotoksik oleh Aruhan Indometasin pada Tikus)

HERU SASONGKO^1,*, AULIA YULFA BRILIAN¹, HARDIANA FEGA OCTAFIANI¹, NABILA RACHMA ALFASINA¹, MUHAMMAD CAHYADI^2,4 & SUTARNO³

¹Department of Pharmacy, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36A Surakarta, Jawa Tengah, Indonesia, 57126

²Department of Animal Science, Faculty of Animal Science, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36A Surakarta, Jawa Tengah, Indonesia, 57126

³Department of Biology, Faculty of Mathematics and Natural Science Universitas Sebelas Maret, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36A Surakarta, Jawa Tengah, Indonesia, 57126

⁴Halal Research Center and Services (HRCS), Institute for Research and Community Service, Universitas Sebelas Maret, Jl. Ir. Sutami No. 36A Surakarta, Jawa Tengah, Indonesia, 57126

Diserahkan: 8 November 2022/Diterima: 20 September 2023

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) potentially induce hepatotoxicity and ulcerative lesions in the stomach. Several studies have been conducted on the benefits of natural resources to overcome the problem of drug side effects. However, the use of fishery resources, such as the eel (Anguilla bicolor), for medicine has not been widely studied. Eels are rich in omega-3 polyunsaturated fatty acids with antioxidant and anti-inflammatory effects. Therefore, this study aims to determine the gastroprotective and hepatoprotective effects of polyunsaturated fatty acids extracted from eel (FaE). The experimental models were 42 male rats divided into seven groups. The experiment was performed for 14 days by orally administering FaE samples. On the 15th day, the rats were orally induced with indomethacin (48 mg/kg). After 8 h of induction, they were euthanized using ketamine and xylazine. Furthermore, blood samples were collected from the animals to measure the levels of aspartate aminotransferase and alanine aminotransferase. Malondialdehyde (MDA) and glutathione (GSH) levels were measured, while the histology of the liver and stomach were examined. The results showed that the administration of FaE from a dose of 1000 mg/kg significantly attenuated the liver and stomach damage caused by indomethacin. The influence of oxidative stress inhibition on damage is characterized by inhibition of the increase in MDA and a decrease in GSH. This research shows that FaE has the potential to inhibit liver and gastric damage due to the use of NSAIDs. However, further investigation needs to be conducted on other specific parameters of the inflammatory mechanism.

Keywords: Drug injury; fish; omega-3; oxidative stress

Abstrak

Dadah anti-radang bukan steroid berpotensi menyebabkan kehepatotoksikan dan lesi ulseratif di dalam perut. Beberapa kajian telah dijalankan tentang kebaikan sumber alam bagi mengatasi masalah kesan sampingan dadah. Walau bagaimanapun, penggunaan sumber berasaskan ikan, seperti belut (Anguilla bicolor), untuk tujuan rawatan belum dikaji dengan meluas. Belut kaya dengan asid lemak tak tepu omega-3, yang mempunyai kesan antioksidan dan anti-radang. Oleh itu, kajian ini bertujuan untuk menentukan kesan gastropelindung dan gastropelindung asid lemak tak tepu yang diekstrak daripada belut (FaE). Model uji kaji terdiri daripada 42 ekor tikus Jantan yang dibahagikan kepada tujuh kumpulan. Uji kaji ini dilakukan selama 14 hari dengan memberikan sampel FaE secara oral. Pada hari ke-15, tikus telah diinduksi dengan indometasin (48 mg/kg) secara oral. Selepas 8 jam induksi, mereka dimatikan menggunakan ketamin dan xilazina. Kemudian, sampel darah dikumpulkan daripada haiwan tersebut untuk mengukur tahap aspartate aminotransferase dan alanine aminotransferase. Tahap malondialdehid (MDA) dan glutation (GSH) diukur, manakala histologi hati dan perut diperiksa. Hasil kajian menunjukkan bahawa pemberian FaE daripada dos 1000 mg/kg dengan ketara melemahkan kerosakan hati dan perut yang disebabkan oleh indometasin. Pengaruh perencatan tekanan oksidatif terhadap kerosakan dicirikan oleh perencatan peningkatan MDA dan penurunan GSH. Penyelidikan ini menunjukkan bahawa FaE mempunyai potensi untuk menghalang kerosakan hati dan gastrik akibat penggunaan NSAID. Walau bagaimanapun, kajian lanjut perlu dijalankan terhadap parameter khusus yang lain tentang mekanisme keradangan.

Kata kunci: Ikan; kecederaan dadah; omega-3; tekanan oksidatif

RUJUKAN

Aboelhadid, S.M., El-Ashram, S., Hassan, K.M., Arafa, W.M. & Darwish, A.B. 2019. Hepato-protective effect of curcumin and silymarin against Eimeria stiedae in experimentally infected rabbits. Livestock Science 221: 33-38. https://doi.org/10.1016/j.livsci.2019.01.011

Ahmed, O.A.A., Fahmy, U.A., Bakhaidar, R., El-Moselhy, M.A., Okbazghi, S.Z., Ahmed, A.S.F., Hammad, A.S.A. & Alhakamy, N.A. 2020. Omega-3 self-nanoemulsion role in gastroprotection against indomethacin-induced gastric injury in rats. Pharmaceutics 12(2): 140. https://doi.org/10.3390/pharmaceutics12020140

Ahn, J.C., Chong, W.S., Na, J.H., Yun, H.B., Shin, K.J., Lee, K.W. & Park, J.T. 2015. An evaluation of major nutrients of four farmed freshwater eel species (Anguilla japonica, A. rostrata, A. bicolor pacifica and A. marmorata). Korean Journal of Fisheries and Aquatic Sciences 48(1): 44-50. https://doi.org/10.5657/KFAS.2015.0044

Ali, F.F. & Rifaai, R.A. 2019. Preventive effect of omega-3 fatty acids in a rat model of stress-induced liver injury. Journal of Cellular Physiology 234(7): 11960-11968. https://doi.org/10.1002/jcp.27848

Arai, T., Chino, N., Zulkifli, S.Z. & Ismail, A. 2012. Notes on the occurrence of the tropical eel Anguilla bicolor bicolor in Peninsular Malaysia, Malaysia. Journal of Fish Biology 80(3): 692-697. https://doi.org/10.1111/j.1095-8649.2011.03154.x

Bagheri, S.M., Zare-Mohazabieh, F., Momeni-Asl, H., Yadegari, M., Mirjalili, A. & Anvari, M. 2018. Antiulcer and hepatoprotective effects of aqueous extract of Plantago ovata seed on indomethacin-ulcerated rats. Biomedical Journal 41(1): 41-45. https://doi.org/10.1016/j.bj.2018.01.001

Beiranvand, M. 2021. A review of the biological and pharmacological activities of mesalazine or 5-aminosalicylic acid (5-ASA): An anti-ulcer and anti-oxidant drug. Inflammopharmacology 29(5): 1279-1290. https://doi.org/10.1007/s10787-021-00856-1

Calder, P.C. 2013. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? British Journal of Clinical Pharmacology 75(3): 645-662. https://doi.org/10.1111/j.1365-2125.2012.04374.x

Carta, G., Murru, E., Banni, S. & Manca, C. 2017. Palmitic acid: Physiological role, metabolism and nutritional implications. Frontiers in Physiology 8: 902. https://www.frontiersin.org/articles/10.3389/fphys.2017.00902

Dias, B.V., Gomes, S.V., da Cruz Castro, M.L., Carvalho, L.C.F., Breguez, G.S., de Souza, D.M.S., de Oliveira Ramos, C., Sant’Ana, M.R., Nakandakari, S.C.B.R., Araujo, C.M., Grabe-Guimarães, A., Talvani, A., Carneiro, C.M., Cintra, D.E.C. & Costa, D.C. 2022. EPA/DHA and linseed oil have different effects on liver and adipose tissue in rats fed with a high-fat diet. Prostaglandins & Other Lipid Mediators 159: 106622. https://doi.org/10.1016/j.prostaglandins.2022.106622

El-Gendy, Z.A., El-Batran, S.A., Youssef, S., Ramadan, A., Hotaby, W.E., Bakeer, R.M. & Ahmed, R.F. 2021. Hepatoprotective effect of Omega-3 PUFAs against acute paracetamol-induced hepatic injury confirmed by FTIR. Human & Experimental Toxicology 40(3): 526-537. https://doi.org/10.1177/0960327120954522

Garrel, C., Alessandri, J.M., Guesnet, P. & Al-Gubory, K.H. 2012. Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development. The International Journal of Biochemistry & Cell Biology 44(1): 123-131. https://doi.org/10.1016/j.biocel.2011.10.007

Grimstad, T., Bjørndal, B., Cacabelos, D., Aasprong, O.G., Janssen, E.A.M., Omdal, R., Svardal, A., Hausken, T., Bohov, P., Portero-Otin, M., Pamplona, R. & Berge, R.K. 2012. Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis in rats. Scandinavian Journal of Gastroenterology 47(1): 49-58. https://doi.org/10.3109/00365521.2011.634025

He, J., Bai, K., Hong, B., Zhang, F. & Zheng, S. 2017a. Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats. International Immunopharmacology 53: 56-62. https://doi.org/10.1016/j.intimp.2017.09.013

He, J., Bai, K., Hong, B., Zhang, F. & Zheng, S. 2017b. Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats. International Immunopharmacology 53: 56-62. https://doi.org/10.1016/j.intimp.2017.09.013

Hidayah, N., Rohman, A., Mustafidah, M. & Irnawati. 2022. Physicochemical characterization and fatty acid profiles of fish oil from milkfish (Chanos chanos F.). Food Research 6(2): 265-270. https://doi.org/10.26656/fr.2017.6(2).222

Hilal Ahmad, M., Fatima, M., Hossain, Mohd. M. & Mondal, A.C. 2018. Determination of potential oxidative damage, hepatotoxicity, and cytogenotoxicity in male Wistar rats: Role of indomethacin. Journal of Biochemical and Molecular Toxicology 32(12): e22226. https://doi.org/10.1002/jbt.22226

Jahangiri, S., Mousavi, S.H., Hatamnejad, M.R., Salimi, M. & Bazrafshan, H. 2022. Prevalence of non-steroidal anti-inflammatory drugs (NSAIDs) use in patients with hypertensive crisis. Health Science Reports 5(1): e483. https://doi.org/10.1002/hsr2.483

Kakisaka, K., Yoshida, Y., Suzuki, Y., Sato, T., Kuroda, H., Miyasaka, A. & Takikawa, Y. 2018. Serum markers for mitochondrial dysfunction and cell death are possible predictive indicators for drug-induced liver injury by direct acting antivirals. Hepatology Research 48(1): 78-86. https://doi.org/10.1111/hepr.12893

Kim, E.K., Cho, J.H., Jeong, A.R., Kim, E.J., Park, D.K., Kwon, K.A., Chung, J.W., Kim, K.O., Kim, J.H., Kim, J.H. & Kim, Y.J. 2017. Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury. Journal of Physiology and Pharmacology 68(1): 69-77.

Kusharto, C.M., Widyasari, R.A.H.E., Budywiryawan, Wiyono, E.S. & Sugengherisuseno. 2014. Nutritive value and fatty acids profile of fresh Indonesian eel (Anguilla bicolor) and kabayaki. Jurnal Sains Kesihatan Malaysia 12(1): 41-46. http://ejournals.ukm.my/jskm/article/view/6993

Leng, S., Winter, T. & Aukema, H.M. 2018. Dietary ALA, EPA and DHA have distinct effects on oxylipin profiles in female and male rat kidney, liver and serum. The Journal of Nutritional Biochemistry 57: 228-237. https://doi.org/10.1016/j.jnutbio.2018.04.002

Liu, K., Yu, J., Xia, Y., Zhang, L.T., Li, S.Y. & Yan, J. 2022. The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro. Chinese Journal of Traumatology 25(6): 379-388. https://doi.org/10.1016/j.cjtee.2022.05.002

Lu, W., Cheng, F., Jiang, J., Zhang, C., Deng, X., Xu, Z., Zou, S., Shen, X., Tang, Y. & Huang, J. 2015. FXR antagonism of NSAIDs contributes to drug-induced liver injury identified by systems pharmacology approach. Scientific Reports 5: 8114. https://doi.org/10.1038/srep08114

Lucas, S. 2016. The pharmacology of Indomethacin. Headache: The Journal of Head and Face Pain 56(2): 436-446. https://doi.org/10.1111/head.12769

Mohamed, Y.T., Naguib, I.A., Abo-Saif, A.A., Elkomy, M.H., Alghamdi, B.S. & Mohamed, W.R. 2022. Role of ADMA/DDAH-1 and iNOS/eNOS signaling in the gastroprotective effect of tadalafil against indomethacin-induced gastric injury. Biomedicine & Pharmacotherapy 150: 113026. https://doi.org/10.1016/j.biopha.2022.113026

Nafsiyah, I., Nurilmala, M. & Abdullah, A. 2018. Nutrient composition of eel Anguilla bicolor bicolor and Anguilla marmorata. Jurnal Pengolahan Hasil Perikanan Indonesia 21(3): 504-512. https://doi.org/10.17844/jphpi.v21i3.24733

Patterson, E., Wall, R., Fitzgerald, G.F., Ross, R.P. & Stanton, C. 2012. Health implications of high dietary Omega-6 polyunsaturated fatty acids. Journal of Nutrition and Metabolism 2012: e539426. https://doi.org/10.1155/2012/539426

Pineda-Peña, E.A., Martínez-Pérez, Y., Galicia-Moreno, M., Navarrete, A., Segovia, J., Muriel, P., Favari, L., Castañeda-Hernández, G. & Chávez-Piña, A.E. 2018. Participation of the anti-inflammatory and antioxidative activity of docosahexaenoic acid on indomethacin-induced gastric injury model. European Journal of Pharmacology 818: 585-592. https://doi.org/10.1016/j.ejphar.2017.11.015

Pineda-Peña, E.A., Jiménez-Andrade, J.M., Castañeda-Hernández, G. & Chávez-Piña, A.E. 2012. Docosahexaenoic acid, an Omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury. European Journal of Pharmacology 697(1): 139-143. https://doi.org/10.1016/j.ejphar.2012.09.049

Salinas-Nolasco, C., Barragán-Zarate, G.S., Lagunez-Rivera, L., Solano, R., Favari, L., Jiménez-Andrade, J.M. & Chávez-Piña, A.E. 2022. Role of LTB4 and nitric oxide in the gastroprotective effect of Prosthechea karwinskii leaves extract in the indomethacin-induced gastric injury in the rat. Natural Product Research 37(5): 819-822.

Sasongko, H., Efendi, N.R., Budihardjo, A., Farida, Y., Amartiwi, T., Rahmawati, A.A., Wicaksono, A. & Sugiyarto. 2017. Solvent and extraction methods effects on the quality of eel (Anguilla bicolor) oil. Journal of Physics: Conference Series 795(1): 012021. https://doi.org/10.1088/1742-6596/795/1/012021

Sasongko, H., Efendi, N.R. & Sugiyarto. 2018. The ethanolic extract of mountain papaya (Vasconcellea pubescens A.DC.) fruit against lipid peroxidation of rat liver tissues. AIP Conference Proceedings 2019(1): 050001. https://doi.org/10.1063/1.5061894

Sasongko, H., Nurrochmad, A., Nugroho, A.E. & Rohman, A. 2022. Indonesian freshwater fisheries’ oil for health and nutrition applications: A narrative review. Food Research 6: 501-511. https://doi.org/10.26656/fr.2017.6(2).362

Sasongko, H., Zulpadly, M.F. & Farida, Y. 2023. Potential fish oil as acute hepatitis candidate by hepatoprotective mechanism: A-review. Journal of Pharmaceutical Science and Clinical Research 8(2):  206-217. https://doi.org/10.20961/jpscr.v8i2.68523

Seid, A.S. & Mamo, E.A. 2022. Overt GI bleeding from a Cameron lesion in an Ethiopian with NSAID use: Case report of an unusual condition. Annals of Medicine and Surgery 75: 103469. https://doi.org/10.1016/j.amsu.2022.103469

Sri Rethinavel, H., Selvaraj, D.B., Balakrishnan, S.J., Vergil Andrews, J.F., Joseph, J.H.M. & Kandasamy, M. 2022. Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder. Heliyon 8(6): e09787. https://doi.org/10.1016/j.heliyon.2022.e09787

Stachowicz, K. 2020. Indomethacin, a nonselective cyclooxygenase inhibitor, does not interact with MTEP in antidepressant-like activity, as opposed to imipramine in CD-1 mice. European Journal of Pharmacology 888: 173585. https://doi.org/10.1016/j.ejphar.2020.173585

Tihista, S. & Echavarría, E. 2018. Effect of omega 3 polyunsaturated fatty acids derived from fish oil in major burn patients: A prospective randomized controlled pilot trial. Clinical Nutrition 37(1): 107-112. https://doi.org/10.1016/j.clnu.2017.01.002

Weydert, C.J. & Cullen, J.J. 2010. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature Protocols 5: 51-66. https://doi.org/10.1038/nprot.2009.197

Yang, J., Ma, Z., Jia, Q., Li, Y., Lu, Y. & Yang, Q. 2021. IRE1α promotes cell apoptosis and an inflammatory response in endoplasmic reticulum stress-induced rheumatoid arthritis fibroblast-Like synovial cells by enhancing autophagy. Sains Malaysiana 51(8): 2583-2593. https://doi.org/10.17576/jsm-2022-5108-18

*Pengarang untuk surat-menyurat: heru_sasongko@staff.uns.ac.id