Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine–induced hepatotoxicity in rats

Fatemeh Dejan , Amineh Daneshi , Javad Rajabi Aslani , Nasrollah Ahmadi , Narges Eskandari Roozbahani , Elaham Rahmanian , Reza Behmanesh , Hamid Reza Gheisari

Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (4) : 544 -552.

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Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (4) : 544 -552. DOI: 10.1002/ame2.12451
ORIGINAL ARTICLE

Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine–induced hepatotoxicity in rats

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Abstract

Background: Complementary medicine is an interesting field for extracting bioactive compounds from various plant and animal sources. The hepatoprotective effect of the methanolic extract of a species of sea cucumber called Holothuria leucospilota in an animal model of liver cancer caused by dimethyl nitrosamine (DMN) was studied.

Methods: Wistar female rats were randomly divided into five groups (n = 12): control (intact), positive control (received 1% DMN [10 mg/kg/week, intraperitoneally] for 12 weeks), and three treatment groups (received 50, 100, and 200 mg/kg/day H. leucospilota extract orally for 12 weeks along with intraperitoneal administration of 1% DMN [10 mg/kg/week]). In all groups, ultrasound was performed on the liver every week to check its density. Blood sampling and liver isolation were performed on three occasions, at 4, 8, and 12 weeks, to check liver enzymes and the histopathological condition of the liver tissue (every week, four animals from each group were randomly selected).

Results: Liver density changes were evident from the eighth week onward in the positive control group. Histopathological results indicated pathologic changes in the positive control group after 4 weeks. The increase in liver enzymes in the positive control group was significantly different from that in the treatment and control groups.

Conclusions: We demonstrated the hepatoprotective effect of H. leucospilota on DMN-induced liver damage in rats using biochemical and histological parameters and ultrasonography. More additional research (in silico or in vitro) is needed to find the exact mechanism and the main biological compound in H. leucospilota.

Keywords

dimethyl nitrosamine / hepatotoxicity / Holothuria leucospilota / sea cucumber

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Fatemeh Dejan, Amineh Daneshi, Javad Rajabi Aslani, Nasrollah Ahmadi, Narges Eskandari Roozbahani, Elaham Rahmanian, Reza Behmanesh, Hamid Reza Gheisari. Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine–induced hepatotoxicity in rats. Animal Models and Experimental Medicine, 2024, 7(4): 544-552 DOI:10.1002/ame2.12451

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References

[1]

Lotfollahzadeh SR, Recio-Boiles A, Babiker HM. Liver Cancer. StatPearls [Internet]. StatPearls Publishing;2022.

[2]

Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification. Adv Cancer Res. 2021;149:1-61.

[3]

Serraino D, Fratino L, Piselli P. Epidemiological aspects of hepatocellular carcinoma. In: Ettorre GM, ed. Hepatocellular Carcinoma. Springer International Publishing;2023:3-9.

[4]

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30.

[5]

Jain D, Chaudhary P, Varshney N, Janmeda P. Carcinogenic effects of N-nitroso compounds in the environment. Environ Conserv J. 2020;21(3):25-41.

[6]

Neuman MG. Hepatotoxicity: mechanisms of liver injury. Liver Diseases: A Multidisciplinary Textbook. 2020;1:75-84.

[7]

Sondhi SM, Singh J, Rani R, Gupta P, Agrawal S, Saxena A. Synthesis, anti-inflammatory and anticancer activity evaluation of some novel acridine derivatives. Eur J Med Chem. 2010;45(2):555-563.

[8]

Bordbar S, Anwar F, Saari N. High-value components and bioactives from sea cucumbers for functional foods—a review. Mar Drugs. 2011;9(10):1761-1805.

[9]

Shiell G. Field observations of juvenile sea cucumbers. SPC Beche-de-Mer Inf Bull. 2004;20:6-11.

[10]

Conand C. Sea cucumber biology, taxonomy, distribution and conservation status. workshop on the conservation of sea cucumbers in the families Holothuriidae and Stichopodidae. 2006.

[11]

Sil’chenko AS, Avilov SA, Kalinin VI, et al. Monosulfated triterpene glycosides from Cucumaria okhotensis Levin et Stepanov, a new species of sea cucumbers from Sea of Okhotsk. Bioorg Khim. 2007;33(1):81-90.

[12]

Zou ZR, Yi YH, Wu HM, Wu JH, Liaw CC, Lee KH. Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert. J Nat Prod. 2003;66(8):1055-1060.

[13]

Rowe FWE, Gates J. Zoological Catalogue of Australia. Australian Government Publishing Service;1983.

[14]

Kamarudin KR, Rehan MM. Morphological and molecular identification of Holothuria (Merthensiothuria) leucospilota and Stichopus horrens from Pangkor Island, Malaysia. Trop Life Sci Res. 2015;26(1):87-99.

[15]

Kamarudin KR, Rehan MM, Bahaman NA. Morphological and molecular identification of sea cucumber species Holothuria scabra, Stichopus horrens and Stichopus ocellatus from Kudat, Sabah, Malaysia. Pertanika J Trop Agr Sci. 2017;40(1):161-171.

[16]

OECD 425– Up-and-Down-Procedure (UDP). 2008.

[17]

Dakrory AI, Fahmy SR, Soliman AM, Mohamed AS, Amer SA. Protective and curative effects of the sea cucumber Holothuria atra extract against DMBA-induced hepatorenal diseases in rats. Biomed Res Int. 2015;2015:563652.

[18]

Thomas L. Clinical Laboratory Diagnostics: Use and Assessment of Clinical Laboratory Results. TH-books Verlagsgesellschaft;1998.

[19]

Lin Y-L, Li Y. Study on the hepatocellular carcinoma model with metastasis. Genes Dis. 2020;7(3):336-350.

[20]

George J, Tsuchishima M, Tsutsumi M. Molecular mechanisms in the pathogenesis of N-nitrosodimethylamine induced hepatic fibrosis. Cell Death Dis. 2019;10(1):18.

[21]

Fujiwara N, Liu P-H, Athuluri-Divakar SK, Zhu S, Hoshida Y. Risk factors of hepatocellular carcinoma for precision personalized care. In: Hoshida Y, ed. Hepatocellular Carcinoma: Translational Precision Medicine Approaches. Springer;2019:3-25.

[22]

Massin C. The holothurians of Easter Island. Bull Inst Roy Sci Nat Belgique Biol. 1996;66:151-178.

[23]

Majid A, Maryam E, Reza DA, Neda S, Ghodrat M. New observation of two sea cucumber species from Abu Musa Island (Persian Gulf, Iran). Eur J Exp Biol. 2012;2(3):611-615.

[24]

Fahmy SR, Mohamed AS. Holoturia arenicola extract modulates bile duct ligation-induced oxidative stress in rat kidney. Int J Clin Exp Pathol. 2015;8(2):1649-1657.

[25]

Zhang SY, Yi YH, Tang HF. Bioactive triterpene glycosides from the sea cucumber Holothuria fuscocinerea. J Nat Prod. 2006;69(10):1492-1495.

[26]

Han H, Yi Y-H, Li L, et al. Triterpene glycosides from sea cucumber Holothuria leucospilota. Chin J Nat Med. 2009;7(5):346-350.

[27]

Silchenko AS, Kalinovsky AI, Avilov SA, et al. Structures and bioactivities of quadrangularisosides A, A(1), B, B(1), B(2), C, C(1), D, D(1)-D(4), and E from the sea cucumber Colochirus quadrangularis: the first discovery of the glycosides, sulfated by C-4 of the terminal 3-O-methylglucose residue. Synergetic effect on colony formation of tumor HT-29 cells of these glycosides with radioactive irradiation. Mar Drugs. 2020;18(8):394.

[28]

Adrian TE, Collin P. The anti-cancer effects of Frondoside A. Mar Drugs. 2018;16(2):64.

[29]

Dhinakaran DI, Lipton AP. Antitumor and antifungal activities of organic extracts of seacucumber Holothuria atra from the southeast coast of India. J Ocean Univ China. 2015;14(1):185-189.

[30]

Mashjoor S, Yousefzadi M, Pishevarzad F. Assessment of anticancer potential of selected Holothuria species. Indian J Tradit Knowl. 2019;18:272-280.

[31]

Tian F, Zhu CH, Zhang XW, et al. Philinopside E, a new sulfated saponin from sea cucumber, blocks the interaction between kinase insert domain-containing receptor (KDR) and alphavbeta3 integrin via binding to the extracellular domain of KDR. Mol Pharmacol. 2007;72(3):545-552.

[32]

Tanaka H. Current role of ultrasound in the diagnosis of hepatocellular carcinoma. J Med Ultrason. 2001;47(2):239-255.

[33]

Song Y, Jin SJ, Cui LH, Ji XJ, Yang FG. Immunomodulatory effect of Stichopus japonicus acid mucopolysaccharide on experimental hepatocellular carcinoma in rats. Molecules. 2013;18(6):7179-7193.

[34]

Subhapradha N, Shanmugam V, Shanmugam A. Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma. Carbohydr Polym. 2017;171:18-26.

[35]

Bhattacharjee A, Giri S, Roy M, Chakraborty A. Correlation of serum lactate dehydrogenase and alkaline phosphatase in different histological grades of head and neck squamous cell carcinoma and premalignant lesions. J Cancer Res Ther. 2018;14(5):934-940.

[36]

Takahashi Y, Dungubat E, Kusano H, et al. Application of immunohistochemistry in the pathological diagnosis of liver tumors. Int J Mol Sci. 2021;22(11):5780.

[37]

Zong J, Fan Z, Zhang Y. Serum tumor markers for early diagnosis of primary hepatocellular carcinoma. J Hepatocell Carcinoma. 2020;7:413-422.

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2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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