The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats

Cevik, Ozge; erdoğan, ömer; Şener, Göksel; Özbeyli, Dilek; Sen, Ali; Cilingir-Kaya, Ozlem Tugce; Ede-Pazarbasi, Seren

doi:10.4274/cjms.2020.2822

The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats

Dilek ÖZBEYLİ, (Marmara Üniversitesi Sağlık Hizmetleri Meslek Yüksekokulu Patoloji Laboratuvar Teknikleri Anabilim Dalı, İstanbul, Türkiye)

Ali ŞEN, (Marmara Üniversitesi Eczacılık Fakültesi, Farmakognozi Anabilim Dalı, İstanbul, Türkiye)

Özge ÇEVİK, (Aydın Adnan Menderes Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Aydın, Türkiye)

Ömer ERDOĞAN, (Aydın Adnan Menderes Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Aydın, Türkiye)

Özlem Tuğçe ÇİLİNGİR KAYA, (Marmara Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji Anabilim Dalı, İstanbul, Türkiye)

Seren EDE, (Fenerbahçe Üniversitesi Eczacılık Fakültesi, Eczacılık Anabilim Dalı, İstanbul, Türkiye)

Göksel ŞENER (Fenerbahçe Üniversitesi Eczacılık Fakültesi, Eczacılık Anabilim Dalı, İstanbul, Türkiye)

Cyprus Journal of Medical Sciences

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Yıl: 2022 Cilt: 7 Sayı: 6 Sayfa Aralığı: 787 - 793 Metin Dili: İngilizce DOI: 10.4274/cjms.2020.2822 İndeks Tarihi: 14-05-2023

The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats

Öz:

BACKGROUND/AIMS: Methotrexate (MTX), a cytotoxic therapeutic agent, is used for the cure of malignancies and rheumatologic disorders. However, the significant side effects of MTX limits its use. In this study, we aim to assess the hepatoprotective properties of Momordica charantia (MC) against MTX-induced liver damaged in rats. MATERIALS AND METHODS: Following one dose of MTX (20 mg/kg), the rats were given either distilled water or MC extract (300 mg/kg, po) for 5 days. After the dissection of the rats, the liver was removed to analyse tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), transforming growth factor β (TGF-β) and 8-hydroxy-2’-deoxy-guanosine (8-OhdG) levels and superoxide dismutase (SOD), catalase (CAT), and caspase-3 activities. The tissues were also examined histopathologically. RESULTS: The hepatic TNF-α, IL-1β, TGF-β, 8-OhdG levels, and Caspase-3 activity in the MTX group were found to be significantly increased compared to the control group. However, MC extract was able to significantly decrease TNF-α, TGF-β, 8-OhdG levels, and Caspase-3 activity. Also, both the SOD and CAT activity of the MTX group decreased compared to the control group. Although only the SOD levels elevated significantly with MC treatment, the SOD and CAT activities of the MC treated group were similar to the control group. Supporting these biochemical parameters, MTX-induced histologic alterations in the liver were also ameliorated via MC treatment. CONCLUSION: Our results demonstrated that MC has a protective role against MTX-induced hepatic tissue injury by reducing apoptosis, oxidative damage, and the expression of pro-inflammatory cytokines.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Malaviya AN. Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story. Int J Rheum Dis. 2016; 19(9): 844-51.
2. Ali N, Rashid S, Nafees S, Hasan SK, Shahid A, Majed F, et al. Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach. Chem Biol Interact. 2017; 25(272): 80-91.
3. Visser K, van der Heijde DM. Risk and management of liver toxicity during methotrexate treatment in rheumatoid and psoriatic arthritis: a systematic review of the literature. Clin Exp Rheumatol. 2009; 27(6): 1017-25.
4. Sener G, Kabasakal L, Yüksel M, Gedik N, Alican Y. Hepatic fibrosis in biliary-obstructed rats is prevented by Ginkgo biloba treatment. World J Gastroenterol. 2005; 11(35): 5444-9.
5. Lee HJ, Cui R, Choi SE, Jeon JY, Kim HJ, Kim TH, et al. Bitter melon extract ameliorates palmitate-induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 cells and high-fat/high-fructose-diet-induced fatty liver. Food Nutr Res. 2018; 62.
6. Ebrahimi R, Sepand MR, Seyednejad SA, Omidi A, Akbariani M, Gholami M, et al. Ellagic acid reduces methotrexate-induced apoptosis and mitochondrial dysfunction via up-regulating Nrf2 expression and inhibiting the IĸBα/NFĸB in rats. Daru. 2019; 27(2): 721-33.
7. Cao Y, Shi H, Sun Z, Wu J, Xia Y, Wang Y, et al. Protective effects of magnesium glycyrrhizinate on methotrexate-induced hepatotoxicity and intestinal toxicity may be by reducing COX-2. Front Pharmacol. 2019; 25 (10): 119.
8. Abdelaziz RM, Abdelazem AZ, Hashem KS, Attia YA. Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats. Naunyn Schmiedebergs Arch Pharmacol. 2020; 393(8): 1405-17.
9. Çakır T, Baştürk A, Polat C, Aslaner A, Durgut H, Şehirli AÖ, et al. Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? Acta Cir Bras. 2015; 30(4): 247-52.
10. Jia S, Shen M, Zhang F, Xie J. Recent advances in momordica charantia: functional components and biological activities. Int J Mol Sci. 2017; 18(12): 2555.
11. Liu JQ, Chen JC, Wang CF, Qiu MH. New cucurbitane triterpenoids and steroidal glycoside from Momordica charantia. Molecules. 2009; 14(12): 4804-13.
12. Baldemir A, Ekinci K, İlgün S, Dalda A, Yetişir H. Evaluation of total phenolic contents and antioxidant capacities of Momordica charantia L. (Bitter gourd) Fruits. Derim. 2018; 35(1): 45-50.
13. Qader SW, Abdulla MA, Chua LS, Najim N, Zain MM, Hamdan S. Antioxidant, total phenolic content and cytotoxicity evaluation of selected Malaysian plants. Molecules. 2011; 16(4): 3433 43.
14. Sagor AT, Chowdhury MR, Tabassum N, Hossain H, Rahman MM, Alam MA. Supplementation of fresh ucche (Momordica charantia L. var. muricata Willd) prevented oxidative stress, fibrosis and hepatic damage in CCl4 treated rats. BMC Complement Altern Med. 2015; 15: 115.
15. Xu X, Shan B, Liao CH, Xie JH, Wen PW, Shi JY. Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice. Int J Biol Macromol. 2015; 81: 538-43.
16. Deng Y, Tang Q, Zhang Y, Zhang R, Wei Z, Tang X, et al. Protective effect of Momordica charantia water extract against liver injury in restraint-stressed mice and the underlying mechanism. Food Nutr Res. 2017; 61(1): 1348864.
17. Raish M, Ahmad A, Ansari MA, Alkharfy KM, Aljenoobi FI, Jan BL, et al. Momordica charantia polysaccharides ameliorate oxidative stress, inflammation, and apoptosis in ethanol-induced gastritis in mucosa through NF-kB signaling pathway inhibition. Int J Biol Macromol. 2018; 111: 193-9.
18. Zeng Y, Guan M, Li C, Xu L, Zheng Z, Li J, et al. Bitter melon (Momordica charantia) attenuates atherosclerosis in apo-E knock-out mice possibly through reducing triglyceride and anti-inflammation. Lipids Health Dis. 2018; 17(1): 251.
19. Gao X, Ohlander M, Jeppsson N, Björk L, Trajkovski V. Changes in antioxidant effects and their relationship to phytonutrients in fruits of sea buckthorn (Hippophae rhamnoides L.) during maturation. J Agric Food Chem. 2000; 48(5): 1485-90.
20. Yıldırım A, Şen A, Doğan A, Bitis L. Antioxidant and anti-inflammatory activity of capitula, leaf and stem extracts of Tanacetum cilicicum (Boiss.) Grierson. Int J Sec Metabolite. 2019; 6(2): 211-22.
21. Zou YH, Liu WT, Zhang JX, Xiang DC. Triterpenoids from the bark of Dysoxylum hainanense and their anti-inflammatory and radical scavenging activity. Fitoterapia. 2017; 121: 159-63.
22. Phosrithong N, Nuchtavorn N. Antioxidant and anti-inflammatory activites of Clerodendrum leaf extracts collected in Thailand. European Journal of Integrative Medicine. 2016; 8(3): 281-5.
23. Trunkey D. Current Therapy of Trauma and Surgical Critical Care 2nd Edition Imprint: Elsevier; 2015.
24. Al Kury LT, Dayyan F, Ali Shah F, Malik Z, Khalil AAK, Alattar A, et al. ginkgo biloba extract protects against methotrexate-induced hepatotoxicity: a computational and pharmacological approach. Molecules. 2020; 25(11): E2540.
25. Owumi SE, Ajijola IJ, Agbeti OM. Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate. Hum Exp Toxicol. 2019; 38(11): 1254-65.
26. Jain V, Pareek A, Paliwal N, Ratan Y, Jaggi AS, Singh N. Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats. Nutr Neurosci. 2014; 17(2): 88-96.
27. Raish M. Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway. Int J Biol Macromol. 2017; 97: 544-51.
28. Ekinci-Akdemir FN, Yildirim S, Kandemir FM, Gülçin İ, Küçükler S, Sağlam YS, et al. The effects of casticin and myricetin on liver damage induced by methotrexate in rats. Iran J Basic Med Sci. 2018; 21(12): 1281-8.
29. Cevik O, Akpinar H, Oba R, Cilingir OT, Ozdemir ZN, Cetinel S, Yoldemir T. The effect of Momordica charantia intake on the estrogen receptors ESRα/ESRβ gene levels and apoptosis on uterine tissue in ovariectomy rats. Mol Biol Rep. 2015; 42(1): 67-177.
30. Kim KB, Lee S, Kang I, Kim JH. Momordica charantia Ethanol Extract Attenuates H₂O₂-Induced Cell Death by Its Antioxidant and Anti-Apoptotic Properties in Human Neuroblastoma SK-N-MC Cells. Nutrients. 2018; 10(10): 1368.
31. Saad DY, Soliman MM, Baiomy AA, Yassin MH, El-Sawy HB. Effects of Karela (Bitter Melon; Momordica charantia) on genes of lipids and carbohydrates metabolism in experimental hypercholesterolemia: biochemical, molecular and histopathological study. BMC Complement Altern Med. 2017; 17(1): 319.
32. Duan ZZ, Zhou XL, Li YH, Zhang F, Li FY, Su-Hua Q. Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway. J Recept Signal Transduct Res. 2015; 35(6): 523-9.
33. Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine. 2019; 86(3): 301-7.
34. Cetin A, Kaynar L, Kocyigit I, Hacioglu SK, Saraymen R, Ozturk A, et al. Role of grape seed extract on methotrexate induced oxidative stress in rat liver. Am J Chin Med. 2008; 36(5): 861-72.
35. Lu KH, Tseng HC, Liu CT, Huang CJ, Chyuan JH, Sheen LY. Wild bitter gourd protects against alcoholic fatty liver in mice by attenuating oxidative stress and inflammatory responses. Food Funct. 2014; 5(5): 1027-37.
36. Wang J, Ryu HK. The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet. Nutr Res Pract. 2015; 9(5): 489-95.
37. Lin KW, Yang SC, Lin CN. Antioxidant constituents from the stems and fruits of Momordica charantia. Food Chem. 2011; 127(2): 609-14.
38. Chiy-Rong C, Yun-Wen L, Yueh-Hsiung K, Jue-Liang H, Chi-I C. Cucurbitane- Type Triterpenoids from Momordica charantia, Natural Product Communications. 2017; 12(6): 889-92.
39. Shivanagoudra SR, Perera WH, Perez JL, Athrey G, Sun Y, Jayaprakasha GK, et al. Cucurbitane-type compounds from Momordica charantia: Isolation, in vitro antidiabetic, anti-inflammatory activities and in silico modeling approaches. Bioorg Chem. 2019; 87: 31-42.

APA	Özbeyli D, Sen A, Cevik O, erdoğan ö, Cilingir-Kaya O, Ede-Pazarbasi S, Şener G (2022). The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. , 787 - 793. 10.4274/cjms.2020.2822
Chicago	Özbeyli Dilek,Sen Ali,Cevik Ozge,erdoğan ömer,Cilingir-Kaya Ozlem Tugce,Ede-Pazarbasi Seren,Şener Göksel The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. (2022): 787 - 793. 10.4274/cjms.2020.2822
MLA	Özbeyli Dilek,Sen Ali,Cevik Ozge,erdoğan ömer,Cilingir-Kaya Ozlem Tugce,Ede-Pazarbasi Seren,Şener Göksel The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. , 2022, ss.787 - 793. 10.4274/cjms.2020.2822
AMA	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. . 2022; 787 - 793. 10.4274/cjms.2020.2822
Vancouver	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. . 2022; 787 - 793. 10.4274/cjms.2020.2822
IEEE	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G "The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats." , ss.787 - 793, 2022. 10.4274/cjms.2020.2822
ISNAD	Özbeyli, Dilek vd. "The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats". (2022), 787-793. https://doi.org/10.4274/cjms.2020.2822

APA	Özbeyli D, Sen A, Cevik O, erdoğan ö, Cilingir-Kaya O, Ede-Pazarbasi S, Şener G (2022). The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. Cyprus Journal of Medical Sciences, 7(6), 787 - 793. 10.4274/cjms.2020.2822
Chicago	Özbeyli Dilek,Sen Ali,Cevik Ozge,erdoğan ömer,Cilingir-Kaya Ozlem Tugce,Ede-Pazarbasi Seren,Şener Göksel The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. Cyprus Journal of Medical Sciences 7, no.6 (2022): 787 - 793. 10.4274/cjms.2020.2822
MLA	Özbeyli Dilek,Sen Ali,Cevik Ozge,erdoğan ömer,Cilingir-Kaya Ozlem Tugce,Ede-Pazarbasi Seren,Şener Göksel The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. Cyprus Journal of Medical Sciences, vol.7, no.6, 2022, ss.787 - 793. 10.4274/cjms.2020.2822
AMA	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. Cyprus Journal of Medical Sciences. 2022; 7(6): 787 - 793. 10.4274/cjms.2020.2822
Vancouver	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats. Cyprus Journal of Medical Sciences. 2022; 7(6): 787 - 793. 10.4274/cjms.2020.2822
IEEE	Özbeyli D,Sen A,Cevik O,erdoğan ö,Cilingir-Kaya O,Ede-Pazarbasi S,Şener G "The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats." Cyprus Journal of Medical Sciences, 7, ss.787 - 793, 2022. 10.4274/cjms.2020.2822
ISNAD	Özbeyli, Dilek vd. "The Protective Effects of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats". Cyprus Journal of Medical Sciences 7/6 (2022), 787-793. https://doi.org/10.4274/cjms.2020.2822