Комбінована гепатопротекторна терапія захворювань печінки
DOI:
https://doi.org/10.30978/MG-2025-1-96Ключові слова:
адеметіонін, силімарин, комбінація гепатопротекторів, переваги та ефективність терапії, Аденомак ПлюсАнотація
Метою комбінованого застосування гепатопротекторів може бути розширення спектра гепатотропної дії або односпрямоване збільшення певного фармакологічного ефекту завдяки сумації або потенціюванню (синергізму). Прикладом сумації ефектів адеметіоніну й силімарину є дослідження, яке вперше показало, що комбінація адеметіоніну та силібініну інгібує як запалення, так і окисний стрес за допомогою двох окремих сигнальних шляхів. І адеметіонін, і силімарин гальмують накопичення жиру в печінці, що підтверджено в пілотному клінічному дослідженні. У хворих на метаболічноасоційовану стеатотичну хворобу печінки при лікуванні комбінацією гепатопротекторів зменшився ступінь стеатозу печінки за даними ультразвукового дослідження. Синергізм дії комбінації виявляється в лікуванні депресії при стеатотичній хворобі печінки й агоністичному впливі на фарнезоїдний рецептор при алкогольній хворобі печінки. Ефективність комбінації при алкогольних гепатопатіях доведена в клінічному дослідженні. Розширення спектра терапевтичної дії при комбінації адеметіоніну та силімарину полягає в тому, що, незважаючи на ефективність обох засобів при токсичних та лікарських ураженнях печінки, є ситуації, коли доцільнішим є призначення певного лікарського засобу. Наприклад, силімарин ефективний при отруєнні блідою поганкою, а адеметіонін — ні. Адеметіонін ефективний при внутрішньопечінковому холестазі, а силімарин — ні. Важливими є й інші властивості силімарину, які також дають змогу розширити спектр ефектів комбінації: антифібротичні, протипухлинні, імуномодулювальні, жовчогінні, противірусні, участь у регуляції апоптозу та регенерації гепатоцитів. І адеметіонін, і силімарин при тривалому лікуванні сприяють збільшенню тривалості життя хворих на цироз печінки. Таким чином, комбінація адеметіоніну та силімарину (препарат «Аденомак Плюс») є патогенетично обґрунтованою, ефективною та перспективною, ґрунтується на доказових дослідженнях.
Посилання
Anstee QM, Day CP. S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J Hepatol. 2012 Nov;57(5):1097-109. http://doi.org/10.1016/j.jhep.2012.04.041. Epub 2012 May 30. PMID: 22659519.
Arold D, Bornstein SR, Perakakis N, Ehrlich S, Bernardoni F. Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK Biobank cohort study. Metabolism. 2024 Oct;159:155983. http://doi.org/10.1016/j.metabol.2024.155983. Epub 2024 Jul 30. PMID: 39089490.
Ashique S, Mohanto S, Kumar N, Nag S, Mishra A, Biswas A, Rihan M, Srivastava S, Bhowmick M, Taghizadeh-Hesary F. Unlocking the possibilities of therapeutic potential of silymarin and silibinin against neurodegenerative Diseases-A mechanistic overview. Eur J Pharmacol. 2024 Oct 15;981:176906. http://doi.org/10.1016/j.ejphar.2024.176906. Epub 2024 Aug 16. PMID: 39154829.
Au AY, Hasenwinkel JM, Frondoza CG. Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro. J Anim Physiol Anim Nutr (Berl). 2013 Apr;97(2):331-41. http://doi.org/10.1111/j.1439-0396.2012.01275.x. Epub 2012 Feb 9. PMID: 22320165.
Bingül İ, Küçükgergin C, Fatih Aydın A, Çevik A, Soluk-Tekkeşin M, Olgaç V, Doğru-Abbasoğlu S, Uysal M. Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs. Gen Physiol Biophys. 2024 Sep;43(5):411-421. http://doi.org/10.4149/gpb_2024021. PMID: 39140684.
Botacin EC, Duarte SMB, Stefano JT, Barbosa MED, Pessoa MG, Oliveira CP. Association between anxiety and depression in metabolic dysfunction-associated steatotic liver disease (MASLD). Arq Gastroenterol. 2024 Jul 19;61:e23128. http://doi.org/10.1590/S0004-2803.24612023-128. PMID: 39045999.
Caballero F, Fernández A, Matías N, Martínez L, Fucho R, Elena M, Caballeria J, Morales A, Fernández-Checa JC, García-Ruiz C. Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-L-methionine and glutathione. J Biol Chem. 2010 Jun 11;285(24):18528-36. http://doi.org/10.1074/jbc.M109.099333. Epub 2010 Apr 15. PMID: 20395294; PMCID: PMC2881778.
Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med. 1989 Oct;55(5):417-9. http://doi.org/10.1055/s-2006-962055. PMID: 2813577.
Cano A, Buqué X, Martínez-Uña M, Aurrekoetxea I, Menor A, García-Rodríguez JL, Lu SC, Martínez-Chantar ML, Mato JM, Ochoa B, Aspichueta P. Methionine adenosyltransferase 1A gene deletion disrupts hepatic very low-density lipoprotein assembly in mice. Hepatology. 2011 Dec;54(6):1975-86. http://doi.org/10.1002/hep.24607. PMID: 21837751; PMCID: PMC3222787.
Capelo-Diz A, Lachiondo-Ortega S, Fernández-Ramos D, Cañas-Martín J, Goikoetxea-Usandizaga N, Serrano-Maciá M, González-Rellan MJ, Mosca L, Blazquez-Vicens J, Tinahones-Ruano A, Fondevila MF, Buyan M, Delgado TC, Gutierrez de Juan V, Ayuso-García P, Sánchez-Rueda A, Velasco-Avilés S, Fernández-Susavila H, Riobello-Suárez C, Dziechciarz B, Montiel-Duarte C, Lopitz-Otsoa F, Bizkarguenaga M, Bilbao-García J, Bernardo-Seisdedos G, Senra A, Soriano-Navarro M, Millet O, Díaz-Lagares Á, Crujeiras AB, Bao-Caamano A, Cabrera D, van Liempd S, Tamayo-Carro M, Borzacchiello L, Gomez-Santos B, Buqué X, Sáenz de Urturi D, González-Romero F, Simon J, Rodríguez-Agudo R, Ruiz A, Matute C, Beiroa D, Falcon-Perez JM, Aspichueta P, Rodríguez-Cuesta J, Porcelli M, Pajares MA, Ameneiro C, Fidalgo M, Aransay AM, Lama-Díaz T, Blanco MG, López M, Villa-Bellosta R, Müller TD, Nogueiras R, Woodhoo A, Martínez-Chantar ML, Varela-Rey M. Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting. Cell Metab. 2023 Aug 8;35(8):1373-1389.e8. http://doi.org/10.1016/j.cmet.2023.07.002. Epub 2023 Jul 31. PMID: 37527658; PMCID: PMC10432853.
De Berardis D, Orsolini L, Serroni N, et al. A comprehensive review on the efficacy of S-adenosyl-L-methionine in major depressive disorder. CNS Neurol Disord Drug Targets. 2016;15(1):35-44. http://doi.org/10.2174/1871527314666150821103825 44.
Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002 Nov;76(5):1172S-6S. http://doi.org/10.1093/ajcn/76/5.1172S. PMID: 12418499.
Dey A, Caro AA, Cederbaum AI. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103. http://doi.org/10.1152/ajpgi.00004.2007.
Doğan D, Meydan İ, Kömüroğlu AU. Protective effect of silymarin and gallic acid against cisplatin-induced nephrotoxicity and hepatotoxicity. Int J Clin Pract. 2022 Apr 16;2022:6541026. http://doi.org/10.1155/2022/6541026. PMID: 35685593; PMCID: PMC9159130.
Dos Santos AC, França TCS, Venzon L, et al. Are silymarin and N-acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS-induced liver injury in mice. J Biochem Mol Toxicol. 2024 Jan;38(1):e23560. http://doi.org/10.1002/jbt.23560. Epub 2023 Oct 20. PMID: 37860953.
Dunn W, Shah V. Pathogenesis of alcoholic liver disease. Clin Liver Dis. 2016;20(3):445-56. http://doi.org/10.1016/j.cld.2016.02.004.
El-Kamary SS, Shardell MD, Abdel-Hamid M, et al. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine. 2009 May;16(5):391-400. http://doi.org/10.1016/j.phymed.2009.02.002. Epub 2009 Mar 19. PMID: 19303273; PMCID: PMC2733865.
Eminzade S, Uraz F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab (Lond). 2008 Jul 5;5:18. http://doi.org/10.1186/1743-7075-5-18. PMID: 18601745; PMCID: PMC2491620.
Enjalbert F, Rapior S, Nouguier-Soulé J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol. 2002;40(6):715-57. http://doi.org/10.1081/clt-120014646. PMID: 12475187.
Fava M, Giannelli A, Rapisarda V, et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Res. 1995;56(3):295-7. http://doi.org/10.1016/0165-1781(95)02656-h.
Fehér J, Deák G, Müzes G, et al. Silymarin kezelés májvédö hatása idült alkoholos májbetegségben [Liver-protective action of silymarin therapy in chronic alcoholic liver diseases]. Orv Hetil. 1989 Dec 17;130(51):2723-7. Hungarian. PMID: 2574842.
Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13. http://doi.org/10.1016/0168-8278(89)90083-4. PMID: 2671116.
Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest. 1982 Nov;47(5):412-26. PMID: 6290784.
Frezza M. Metanalisi dei trial terapeutici con ademetionina nel trattamento della colestasi intraepatica [A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. Ann Ital Med Int. 1993 Oct;8 Suppl:48S-51S. Italian. PMID: 8117521.
Giangrandi I, Dinu M, Pagliai G, et al. Efficacy of oral supplementation with silymarin and s-adenosyl-l-methionine in patients with non-alcoholic fatty liver disease — a pilot study. Altern Integr Med. 2016;5(4):224. http://doi.org/10.4172/2327-5162.1000224.
Guo T, Chang L, Xiao Y, Liu Q. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS One. 201;10(3):e0122124. http://doi.org/10.1371/journal.pone.0122124.
Gür FM, Bilgiç S. Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel. Tissue Cell. 2023 Aug;83:102158. http://doi.org/10.1016/j.tice.2023.102158. Epub 2023 Jul 7. PMID: 37459721.
Hardy ML, Coulter I, Morton SC, Favreau J, Venuturupalli S, Chiappelli F, Rossi F, Orshansky G, Jungvig LK, Roth EA, Suttorp MJ, Shekelle P. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evid Rep Technol Assess (Summ). 2003 Aug;(64):1-3. PMID: 12899148; PMCID: PMC4781303.
Kasper P, Lang S, Steffen HM, Demir M. Management of alcoholic hepatitis: A clinical perspective. Liver Int. 2023 Oct;43(10):2078-2095. http://doi.org/10.1111/liv.15701. Epub 2023 Aug 22. PMID: 37605624.
Kim J, Gao C, Guo P, Sheng J, Wang J. A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis. Cell Commun Signal. 2024 Jun 18;22(1):334. http://doi.org/10.1186/s12964-024-01700-z. PMID: 38890646; PMCID: PMC11184736.
Kim JY, Suh JW, Ji GE. Evaluation of S-adenosyl-l-methionine production by Bifidobacterium bifidum BGN4. Food Sci Biotechnol. 2008;17:184-7. https://koreascience.kr/article/JAKO200833338360303.page.
Li M, Luo Q, Tao Y, Sun X, Liu C. Pharmacotherapies for Drug-Induced Liver Injury: A Current Literature Review. Front Pharmacol. 2022 Jan 5;12:806249. http://doi.org/10.3389/fphar.2021.806249. PMID: 35069218; PMCID: PMC8766857.
Liang W, Zhong K, Lai T, et al. Causal relationship between depression and metabolic dysfunction-associated steatotic liver disease: a bidirectional Mendelian randomized study. Front Psychiatry. 2024 Jun 6;15:1384003. http://doi.org/10.3389/fpsyt.2024.1384003. PMID: 38903646; PMCID: PMC11187267.
Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol. 2003 Oct;37(4):336-9. http://doi.org/10.1097/00004836-200310000-00013. PMID: 14506392.
Mao H. Hepatoprotective effect of S-ademetionine in the treatment of intrahepatic cholestasis through farnesoid X receptor mechanism in rats. J Biomol Res Ther. 2019;8:176. http://doi.org/10.35248/2167-7956.19.8.176.
Marjani M, Fahim F, Sadr M, Kazempour Dizaji M, Moniri A, Khabiri S, Tabarsi P, Velayati AA. Evaluation of Silymarin for management of anti-tuberculosis drug induced liver injury: a randomized clinical trial. Gastroenterol Hepatol Bed Bench. 2019 Spring;12(2):138-142. PMID: 31191838; PMCID: PMC6536020.
Mastron JK, Siveen KS, Sethi G, Bishayee A. Silymarin and hepatocellular carcinoma: a systematic, comprehensive, and critical review. Anticancer Drugs. 2015 Jun;26(5):475-86. http://doi.org/10.1097/CAD.0000000000000211. PMID: 25603021.
Mato JM, Cámara J, Fernández de Paz J, Caballería L, Coll S, Caballero A, García-Buey L, Beltrán J, Benita V, Caballería J, Solà R, Moreno-Otero R, Barrao F, Martín-Duce A, Correa JA, Parés A, Barrao E, García-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodés J. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999 Jun;30(6):1081-9. http://doi.org/10.1016/s0168-8278(99)80263-3. PMID: 10406187.
Ni X, Wang H. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD). Am J Transl Res. 2016 Feb 15;8(2):1073-81. PMID: 27158393; PMCID: PMC4846950.
Noureddin M, Mato JM, Lu SC. Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp Biol Med (Maywood). 2015;240(6):809-20. http://doi.org/10.1177/1535370215579161.
Okovityi SV, Raikhelson KL, Prikhodko VA. Combined hepatoprotective pharmacotherapy for liver disease. Experimental and Clinical Gastroenterology. 2022;(7):5-20. In Russian. https://doi.org/10.31146/1682-8658-ecg-203-7-5-20.
Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol. 2002;5(4):287-94. http://doi.org/10.1017/S1461145702003085.
Pannu A, Sharma PC, Thakur VK, Goyal RK. Emerging role of flavonoids as the treatment of depression. Biomolecules. 2021 Dec 3;11(12):1825. http://doi.org/10.3390/biom11121825. PMID: 34944471; PMCID: PMC8698856.
Pascale RM, Simile MM, Calvisi DF, Feo CF, Feo F. S-Adenosylmethionine: from the discovery of its inhibition of tumorigenesis to its use as a therapeutic agent. Cells. 2022 Jan 25;11(3):409. http://doi.org/10.3390/cells11030409. PMID: 35159219; PMCID: PMC8834208.
Peng TR, Cheng HY, Wu TW. S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis. Gen Hosp Psychiatry. 2024;86:118-26. http://doi.org/10.1016/j.genhosppsych.2024.01.001.
Rostamian S, Heidari-Soureshjani S, Sherwin CMT. The therapeutic effect of silymarin and silibinin on depression and anxiety disorders and possible mechanism in the brain: a systematic review. Cent Nerv Syst Agents Med Chem. 2023;23(2):86-94. http://doi.org/10.2174/1871524923666230823094403. PMID: 37612866.
Saba P, Galeone F, Salvadorini F. Therapeutic action of silymarin on chronic hepatopathies caused by psychopharmaceuticals. Gazz Med Ital. 1976;135:236-51.
Santini D, Vincenzi B, Massacesi C, et al. S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury. Anticancer Res. 2003 Nov-Dec;23(6D):5173-9. PMID: 14981985.
Sukhanov DS. [Antioxidant properties of remaxol, reamberin, and ademetionine in patients with drug-induced liver injury on the background of antituberculous therapy]. Eksp Klin Farmakol. 2013;76(4):45-8. PMID: 23762990.
Talebi A, Soltani R, Khorvash F, Jouabadi SM. The effectiveness of silymarin in the prevention of anti-tuberculosis drug-induced hepatotoxicity: a randomized controlled clinical trial. Int J Prev Med. 2023 Apr 26;14:48. http://doi.org/10.4103/ijpvm.ijpvm_81_22. PMID: 37351038; PMCID: PMC10284206.
Terzi F, Ciftci MK. Protective effect of silymarin on tacrolimus-induced kidney and liver toxicity. BMC Complement Med Ther. 2022 Dec 13;22(1):331. http://doi.org/10.1186/s12906-022-03803-x. PMID: 36514062; PMCID: PMC9746137.
Testino G, Leone S, Ansaldi F, Borro P. Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. Minerva Gastroenterol Dietol. 2013 Dec;59(4):341-56. PMID: 24212353.
Tian YM, Dou LP, Yao S, Yao ZL, Zhang QF, Yu L, Jing Y. [Protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapeutic agents]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Oct;21(5):1305-8. Chinese. doi: 10.7534/j.issn.1009-2137.2013.05.044. PMID: 24156455. https://pubmed.ncbi.nlm.nih.gov/24156455/
Tighe SP, Akhtar D, Iqbal U, Ahmed A. Chronic liver disease and silymarin: a biochemical and clinical review. J Clin Transl Hepatol. 2020 Dec 28;8(4):454-8. http://doi.org/10.14218/JCTH.2020.00012. Epub 2020 Oct 16. PMID: 33447529; PMCID: PMC7782115.
Ullah H, Di Minno A, Esposito C. Efficacy of a food supplement based on S-adenosyl methionine and probiotic strains in subjects with subthreshold depression and mild-to-moderate depression: A monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial. Biomed Pharmacother. 2022;156:113930. http://doi.org/10.1016/j.biopha.2022.113930.
Ullah H, Khan A, Rengasamy KRR, Di Minno A, Sacchi R, Daglia M. The Efficacy of S-Adenosyl Methionine and Probiotic Supplementation on Depression: A Synergistic Approach. Nutrients. 2022 Jul 1;14(13):2751. http://doi.org/10.3390/nu14132751. PMID: 35807931; PMCID: PMC9268496.
Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Long-term (23 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol. 1997 Apr;26(4):871-9. http://doi.org/10.1016/s0168-8278(97)80255-3. PMID: 9126802.
Venugopal DC, Viswanathan P, Ravindran S, et al. Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and in vitro analysis. Mol Biol Rep. 2024 Feb 15;51(1):303. http://doi.org/10.1007/s11033-023-09177-8. PMID: 38356030.
Vitetta L, Bambling M, Alford H. The gastrointestinal tract microbiome, probiotics, and mood. Inflammopharmacology. 2014;22:333-9. http://doi.org/10.1007/s10787-014-0216-x.
Wagoner J, Negash A, Kane OJ, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology. 2010 Jun;51(6):1912-21. http://doi.org/10.1002/hep.23587. PMID: 20512985; PMCID: PMC2909978.
Wei F, Liu SK, Liu XY, Li ZJ, Li B, Zhou YL, Zhang HY, Li YW. Meta-analysis: silymarin and its combination therapy for the treatment of chronic hepatitis B. Eur J Clin Microbiol Infect Dis. 2013 May;32(5):657-69. http://doi.org/10.1007/s10096-012-1789-1. Epub 2012 Dec 18. PMID: 23247631.
Wortham M, He L, Gyamfi M, Copple BL, Wan YJ. The transition from fatty liver to NASH associates with SAMe depletion in db/db mice fed a methionine choline-deficient diet. Dig Dis Sci. 2008 Oct;53(10):2761-74. http://doi.org/10.1007/s10620-007-0193-7. Epub 2008 Feb 26. PMID: 18299981; PMCID: PMC3991247.
Wu J, Wen L, Liu X, et al. Silybin: A review of its targeted and novel agents for treating liver diseases based on pathogenesis. Phytother Res. 2024 Dec;38(12):5713-40. http://doi.org/10.1002/ptr.8347. Epub 2024 Sep 23. PMID: 39310970.
Xu J, Wang X, Xu W, Zhang Y, Pan L, Gao J. The protective effect of S-adenosylmethionine on chronic adolescent stress-induced depression-like behaviors by regulating gut microbiota. Eur J Pharmacol. 2024 Nov 5;982:176939. http://doi.org/10.1016/j.ejphar.2024.176939. Epub 2024 Aug 23. PMID: 39182548.
Yakut S, Atcalı T, Çaglayan C, Ulucan A, Kandemir FM, Kara A, Anuk T. Therapeutic potential of silymarin in mitigating paclitaxel-induced hepatotoxicity and nephrotoxicity: insights into oxidative stress, inflammation, and apoptosis in Rats. Balkan Med J. 2024 May 3;41(3):193-205. http://doi.org/10.4274/balkanmedj.galenos.2024.2024-1-60. PMID: 38700358; PMCID: PMC11077923.
Yang W, Liang Z, Wen C, Jiang X, Wang L. Silymarin protects against acute liver injury induced by acetaminophen by downregulating the expression and activity of the CYP2E1 enzyme. Molecules. 2022 Dec 13;27(24):8855. http://doi.org/10.3390/molecules27248855. PMID: 36557984; PMCID: PMC9784215.
Yi M, Manzoor M, Yang M, Zhang H, Wang L, Zhao L, Xiang L, Qi J. Silymarin targets the FXR protein through microbial metabolite 7-keto-deoxycholic acid to treat MASLD in obese mice. Phytomedicine. 2024 Oct;133:155947. http://doi.org/10.1016/j.phymed.2024.155947. Epub 2024 Aug 8. PMID: 39178642.
Yokouchi C, Nishimura Y, Goto H, Sato M, Hidoh Y, Takeuchi K, Ishii Y. Reduction of fatty liver in rats by nicotinamide via the regeneration of the methionine cycle and the inhibition of aldehyde oxidase. J Toxicol Sci. 2021;46(1):31-42. http://doi.org/10.2131/jts.46.31. PMID: 33408299.
Zhang C, Sui Y, Liu S, Yang M. Anti-viral activity of bioactive molecules of silymarin against -COVID 19 via in silico studies. Pharmaceuticals (Basel). 2023 Oct 17;16(10):1479. http://doi.org/10.3390/ph16101479. PMID: 37895950; PMCID: PMC10610370.
Zhao X, Wang H, Yang Y, Gou Y, Wang Z, Yang D, Li C. Protective Effects of Silymarin Against D-Gal/LPS-Induced Organ Damage and Inflammation in Mice. Drug Des Devel Ther. 2021 May 4;15:1903-1914. http://doi.org/10.2147/DDDT.S305033. PMID: 33976540; PMCID: PMC8106468.
Zhou S, You H, Qiu S, Yu D, Bai Y, He J, Cao H, Che Q, Guo J, Su Z. A new perspective on NAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR). Biomed Pharmacother. 2022 Oct;154:113577. http://doi.org/10.1016/j.biopha.2022.113577. Epub 2022 Aug 19. PMID: 35988420.
Zhu SS, Dong Y, Gan Y, et al. [Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2010 Apr;24(2):136-8. Chinese. PMID: 21110437.
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