Acute toxicity and hepatoprotective effect of Arum maculatum on rat liver cirrhosis induced with thioacetamide

1 S. Salama, C. S. Kue, H. Mohamad, F. Omer, M. Y. Ibrahim, M. Abdulla, H. Ali, A. Mariod and S. N. Jayash, Hepatoprotective potential of a novel quinazoline derivative in thioacetamide-induced liver toxicity, Front. Pharmacol. 13 (2022) Article ID 943340 (14 pages); https://doi.org/10.3389/fphar.2022.943340 Search in Google Scholar

2 K. Vyas and M. M. Patel, Insights on drug and gene delivery systems in liver fibrosis, AJPS 18(2) (2023) Article ID 100779 (24 pages); https://doi.org/10.1016/j.ajps.2023.100779 Search in Google Scholar

3 B. S. da Silva, A. M. B. Paulino, M. Taffarel, I. G. Borba, L. O. Telles, V. V. Lima, D. H. Aguiar, M. C. Dias, A. F. Nascimento, V. D. G. Sinhorin, R. de Azevedo Melo Luvizotto and G. F. Bomfim, High sucrose diet attenuates oxidative stress, inflammation and liver injury in thioacetamide-induced liver cirrhosis, Life Sci. 267 (2021) Article ID 118944 (8 pages); https://doi.org/10.1016/j.lfs.2020.118944 Search in Google Scholar

4 F. D. R. Al-Baiaty, A. Ismail, Z. Abdul Latiff, K. N. Muhammad Nawawi, R. A. Raja Ali and N. M. Mokhtar, Possible hepatoprotective effect of tocotrienol-rich fraction vitamin E in non-alcoholic fatty liver disease in obese children and adolescents, Front. Pediatr. 9 (2021) Article ID 667247 (12 pages); https://doi.org/10.3389/fped.2021.667247 Search in Google Scholar

5 S.-H. Ra, R.-H. Shin, H.-C. Ri, J.-H. Ri, H.-C. Ri and Ae-J. Ri, Effect of lesimarin against thioacet-amide-induced liver cirrhosis in rat, Braz. J. Pharm. Sci. 55 (2019) e17821 (9 pages); https://doi.org/10.1590/s2175-97902019000217821 Search in Google Scholar

6 D. Ezhilarasan, Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models, Environ. Toxicol. Pharmacol. 99 (2023) Article ID 104093; https://doi.org/10.1016/j.etap.2023.104093 Search in Google Scholar

7 S. Raghunandhakumar, D. Ezhilarasan and K. Shree Harini, Thymoquinone protects thioacet-amide-induced chronic liver injury by inhibiting TGF-β1/Smad3 axis in rats, J. Biochem. Mol. Toxicol. 38(4) (2024) e23694; https://doi.org/10.1002/jbt.23694 Search in Google Scholar

8 H. Goel, R. L. Printz, V. R. Pannala, M. D. M. AbdulHameed and A. Wallqvist, Probing liver injuries induced by thioacetamide in human in vitro pooled hepatocyte experiments, Int. J. Mol. Sci. 25(6) (2024) Article ID 25063265 (21 pages); https://doi.org/10.3390/ijms25063265 Search in Google Scholar

9 A. S. Derin and A. Kamaran, Evaluation of advanced glycation end products and other biochemical parameters in patients with leukemia, J. Kufa Chem. Sci. 2(10) (2023) Article ID e13365 (17 pages); https://doi.org/10.36329/jkcm/2023/v2.i10.13365 Search in Google Scholar

10 A. Ravichandra and R. F. Schwabe, Mouse Models of Liver Fibrosis, in Myofibroblasts: Methods Protocols (Eds. B. Hinz and D. Lagares), Methods in Molecular Biology (MIMB Vol. 2299), Springer Nature, London 2021, pp. 339–356. Search in Google Scholar

11 L. Sun, Q. Wu, Y. Nie, N. Cheng, R. Wang, G. Wang, D. Zhang, H. He, R. D. Ye and F. Qian, A role for MK2 in enhancing neutrophil-derived ROS production and aggravating liver ischemia/reper-fusion injury, Front. Immunol. 9 (2018) Article ID e02610 (13 pages); https://doi.org/10.3389/fimmu.2018.02610 Search in Google Scholar

12 V. Singh and S. Ubaid, Role of silent information regulator 1 (SIRT1) in regulating oxidative stress and inflammation, Inflammation 43(5) (2020) Article ID 9 (9 pages); https://doi.org/10.1007/s10753-020-01242-9 Search in Google Scholar

13 F. D. Gratte, S. Pasic, N. D. B. A. Bakar, J. Gogoi-Tiwari, X. Liu, R. Carlessi, T. Kisseleva, D. A. Brenner, G. A. Ramm and J. K. Olynyk, Previous liver regeneration induces fibro-protective mechanisms during thioacetamide-induced chronic liver injury, Int. J. Biochem. Cell Biol. 134 (2021) Article ID 105933 (10 pages); https://doi.org/10.1016/j.biocel.2021.105933 Search in Google Scholar

14 S. H. Shareef, I. A. A. Ibrahim, A. R. Alzahrani, M. H. Al-Medhtiy and M. A. Abdulla, Hepatoprotective effects of methanolic extract of green tea against thioacetamide-induced liver injury in Sprague Dawley rats, Saudi J. Biol. 29(1) (2022) Article ID 228598 (9 pages); https://doi.org/10.1016/j.sjbs.2021.09.023 Search in Google Scholar

15 G. Bilir, M. Sarıahmet and D. Ekinci, Purification and characterization of glutathione reductase enzyme from Arum maculatum leaf, Black Sea J. Agr. 6(3) (2023) Article ID 2937285 (5 pages); https://doi.org/10.47115/bsagriculture.1247272 Search in Google Scholar

16 N. Comlekcioglu, S. Çolak and A. Aygan, A study on the bioactivity of plant extracts obtained from Arum maculatum leaves by different extraction techniques, Prehr. Tehnol. Biotehnol. Nutr. 16(1–2) (2021) Article ID 384898 (5 pages); https://doi.org/10.31895/hcptbn.16.1-2.6 Search in Google Scholar

17 E. Kozuharova, Z. Naychov, V. Kochmarov, N. Benbassat, M. Gibernau and G. Momekov, The potential of Arum spp. as a cure for hemorrhoids: Chemistry, bioactivities, and application, Adv. Trad. Med. 20(2) (2020) Article ID 13596 (8 pages); https://doi.org/10.1007/s13596-020-00425-x Search in Google Scholar

18 M. Karaköse, An ethnobotanical study of medicinal plants in Güce district, north-eastern Turkey, Plant. Divers. 44(6) (2022) Article ID 2128461 (20 pages); https://doi.org/10.1016/j.pld.2022.03.005 Search in Google Scholar

19 R. Farahmandfar, R. E. Kenari, M. Asnaashari, D. Shahrampour and T. Bakhshandeh, Bioactive compounds, antioxidant and antimicrobial activities of Arum maculatum leaves extracts as affected by various solvents and extraction methods, Food Sci. Nutr. 7(2) (2019) Article ID 815 (10 pages); https://doi.org/10.1002/fsn3.815 Search in Google Scholar

20 B. Ergene and M. Karaaslan, Food, medicine or a poisonous plant: Arum maculatum L., J. Res. Pharm. 27(2) (2023) Article ID 332 (14 pages); http://doi.org/10.29228/jrp.332 Search in Google Scholar

21 Z. A. Amin, M. Bilgen, M. A. Alshawsh, H. M. Ali, A. H. A. Hadi and M. A. Abdulla, Protective role of Phyllanthus niruri extract against thioacetamide-induced liver cirrhosis in rat model, Evid. Based Complement. Alternat. Med. 2012 (2012) Article ID 241583 (9 pages); https://doi.org/10.1155/2012/241583 Search in Google Scholar

22 F. A. Kadir, N. M. Kassim, M. A. Abdulla and W. A. Yehye, Hepatoprotective role of ethanolic extract of Vitex negundo in thioacetamide-induced liver fibrosis in male rats, Evid. Based Complement. Alternat. Med. 2013 (2013) Article ID 739850 (9 pages); https://doi.org/10.1155/2013/739850 Search in Google Scholar

23 S. S. Alkiyumi, M. A. Abdullah, A. S. Alrashdi, S. M. Salama, S. I. Abdelwahab and A. H. A. Hadi, Ipomoea aquatica extract shows protective action against thioacetamide-induced hepatotoxicity, Molecules 17(5) (2012) Article ID e56146 (9 pages); https://doi.org/10.3390/molecules17056146 Search in Google Scholar

24 S. M. Salama, M. A. Abdulla, A. S. AlRashdi, S. Ismail, S. S. Alkiyumi and S. Golbabapour, Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats, BMC Complement. Alternat. Ther. 13 (2013) Article ID 56 (17 pages); https://doi.org/10.1186/1472-6882-13-56 Search in Google Scholar

25 W. N. Abood, N. A. Al-Henhena, A. Najim Abood, M. M. Al-Obaidi, S. Ismail, M. A. Abdulla and R. Al Batran, Wound-healing potential of the fruit extract of Phaleria macrocarpa, Bosnian J. Basic Med. Sci. 15(2) (2015) Article ID 39 (5 pages); https://doi.org/10.17305/bjbms.2015.39 Search in Google Scholar

26 P. Zhu, L. Fan, X. Yan and J. Li, Advances of α-linolenic acid: Sources, extraction, biological activity and its carrier, Trends Food Sci. Technol. 152 (2024) Article ID 104676 (15 pages); https://doi.org/10.1016/j.tifs.2024.104676 Search in Google Scholar

27 W. Huang, X. Guo, C. Wang, A. Alzhan, Z. Liu, X. Ma and Q. Shu, α-Linolenic acid induces apoptosis, inhibits the invasion and metastasis, and arrests cell cycle in human breast cancer cells by inhibiting fatty acid synthase, J. Funct. Foods 92 (2022) Article ID 105041(19 pages); https://doi.org/10.1016/j.jff.2022.105041 Search in Google Scholar

28 I. Djuricic and P. C. Calder, Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: An update for 2021, Nutrients 13(7) (2021) Article ID 2421 (23 pages); https://doi.org/10.3390/nu13072421 Search in Google Scholar

29 M. Alagawany, S. S. Elnesr, M. R. Farag, K. El-Sabrout, O. Alqaisi, M. A. Dawood, H. Soomro and S. A. Abdelnour, Nutritional significance and health benefits of omega-3, -6, and -9 fatty acids in animals, Anim. Biotechnol. 33(7) (2022) Article ID 1869562 (12 pages); https://doi.org/10.1080/10495398.2020.1869562 Search in Google Scholar

30 S. Zhu, W. Jiao, Y. Xu, L. Hou, H. Li, J. Shao, X. Zhang, R. Wang and D. Kong, Palmitic acid inhi bits prostate cancer cell proliferation and metastasis by suppressing the PI3K/Akt pathway, Life Sci. 286 (2021) Article ID 120046 (13 pages); https://doi.org/10.1016/j.lfs.2021.120046 Search in Google Scholar

31 P. Sirikhansaeng, T. Tanee, R. Sudmoon and A. Chaveerach, Major phytochemical as γ-sitosterol disclosing and toxicity testing in Lagerstroemia species, Evid. Based Complement. Alternat. Med. 2017 (2017) Article ID 7209851 (10 pages); https://doi.org/10.1155/2017/7209851 Search in Google Scholar

32 H. F. Shen, Y. Liu, P. P. Qu, Y. Tang, B. B. Li and G. L. Cheng, MiR-361-5p/abca1 and MiR-196-5p/arhgef12 axis involved in γ-sitosterol inducing dual anti-proliferative effects on bronchial epithelial cells of chronic obstructive pulmonary disease, Int. J. Chron. Obstruct. Pulmon. Dis. 6 (2021) Article ID 326015 (13 pages); https://doi.org/10.2147/COPD.S326015 Search in Google Scholar

33 F. Galli, M. Bonomini, D. Bartolini, L. Zatini, G. Reboldi, G. Marcantonini, G. Gentile, V. Sirolli and N. Di Pietro, Vitamin E (alpha-tocopherol) metabolism and nutrition in chronic kidney disease, Antioxidants 11(5) (2022) Article ID 990 (19 pages); https://doi.org/10.3390/antiox11050989 Search in Google Scholar

34 G. Fatima, A. Dzupina, A. A. Mahdi, J. Fedacko, A. Magomedova and N. G. Yousif, Role of vita-min-E as a vital nutrient in health and diseases, Ind. J. Clin. Biochem. (2025) Article ID 12291 (14 pages), in press; https://doi.org/10.1007/s12291-025-01309-0 Search in Google Scholar

35 A. M. H. Gowifel, M. G. Khalil, S. A. Nada, S. A. Kenawy, K. A. Ahmed, M. M. Salama and M. M. Safar, Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: Impact on TGF-β/Smad3 and NF-κB signaling pathways, Toxicol. Mech. Methods 30 (2020) 620–633; https://doi.org/10.1080/15376516.2020.1801926 Search in Google Scholar

36 S. W. Bradosty, S. W. Hamad, N. F. S. Agha, F. K. Shaikh, N. M. Qadir Nanakali, P. Y. Aziz, N. A. Salehen, F. Suzergoz and M. A. Abdulla, In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide, Environ. Toxicol. 36(12) (2021) Article ID 23353 (9 pages); https://doi.org/10.1002/tox.23353 Search in Google Scholar

37 W. N. Abood, S. W. Bradosty, F. K. Shaikh, N. A. Salehen, R. Farghadani, N. F. S. Agha, M. H. Al-Medhtiy, T. D. A. Kamil, A. S. Agha and M. A. Abdulla, Garcinia mangostana peel extracts exhibit hepatoprotective activity against thioacetamide-induced liver cirrhosis in rats, J. Funct. Foods 74 (2020) Article ID 104200 (17 pages); https://doi.org/10.1016/j.jff.2020.104200 Search in Google Scholar

38 A. A. Sakul, M. E. Okur, S. Ayla, B. Daylan, A. E. Karadag, S. Batur, E. M. Ozdemir, E. Altinalan and M. Y. Gunal, Wound healing activity of Arum maculatum, Medeni Med. J. 38(1) (2023) Article ID 73368 (7 pages); https://doi.org/10.4274/MMJ.galenos.2022.73368 Search in Google Scholar

39 M. Hong, S. Li, N. Wang, H.-Y. Tan, F. Cheung and Y. Feng, A biomedical investigation of the hepatoprotective effect of radix salviae miltiorrhizae and network pharmacology-based prediction of the active compounds and molecular targets, Int. J. Mol. Sci. 18(3) (2017) Article ID 620 (18 pages); https://doi.org/10.3390/ijms18030620 Search in Google Scholar

40 S. H. Shareef, M. H. Al-Medhtiy, A. S. Al Rashdi, P. Y. Aziz and M. A. Abdulla, Hepatoprotective effect of pinostrobin against thioacetamide-induced liver cirrhosis in rats, Saudi J. Biol. Sci. 30(1) (2023) Article ID 103506 (10 pages); https://doi.org/10.1016/j.sjbs.2022.103506 Search in Google Scholar

41 H. S. Al-Shmgani, Z. H. M. Kadri, M. M. Al-Halbosiy and Y. H. Dewir, Phytochemical analysis, cytotoxicity and antioxidant activity of cuckoo pint (Arum maculatum) leaf extract, Acta Biol. Szeged 63(2) (2019) Article ID 3084 (5 pages); https://doi.org/10.14232/abs.2019.2.119-124 Search in Google Scholar

42 I. Kandilarov, P. Gardjeva, M. Georgieva-Kotetarova, H. Zlatanova, N. Vilmosh, I. Kostadinova, M. Katsarova, K. Atliev and S. Dimitrova, Effect of plant extracts combinations on TNF-α, IL-6 and IL-10 levels in serum of rats exposed to acute and chronic stress, Plants 12 (2023) Article ID 3049 (16 pages); https://doi.org/10.3390/plants12173049 Search in Google Scholar

43 L. Luo, Z. Zhou, J. Xue, Y. Wang, J. Zhang, X. Cai, Y. Liu and F. Yang, Bletilla striata polysaccharide has a protective effect on intestinal epithelial barrier disruption in TAA-induced cirrhotic rats, Exp. Ther. Med. 16(3) (2018) Article ID 6430 (7 pages); https://doi.org/10.3892/etm.2018.6430 Search in Google Scholar