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Planta Med 2023; 89(06): 584-607
DOI: 10.1055/a-1969-2440
Biological and Pharmacological Activity
Reviews

Use of Milk Thistle in Farm and Companion Animals: A Review

Doriana Eurosia Angela Tedesco
Department of Environmental Science and Policy, University of Milan, Italy
,
Alessandro Guerrini
Department of Environmental Science and Policy, University of Milan, Italy
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Abstract

Milk thistle, Silybum marianum, is a medicinal plant grown for its bioactive compounds with well-documented antioxidant and hepatoprotective properties. Milk thistle has a well-established pharmacological reputation for treatments of human liver disease, but it is also used in animals. This review summarizes the experimental evidence of milk thistleʼs effects on animals when administered as silymarin extract (feed additive) or a feed ingredient, if administered as seed or expeller/cake with the seed residue still containing the bioactive components. The use as a feed additive or feed ingredient is motivated by the complexity of silymarin registration as a veterinary drug. In farm animals, the drug improves the animalsʼ performance and product quality and oxidative stability, supports liver function during the productive life-cycle, improves gut-health and morphology, and can reduce intestinal pathogens. In dogs and cats, the treatment is focused on acute and chronic liver diseases including the detoxification processes and support of drug treatments including chemotherapy. In equine athletes, milk seed cake showed positive effects and a faster return of cortisol to the resting values before exercise occurred. In aquaculture, it confirms its usefulness in supporting animal health and performance. In certain studies it is not clear what has been administered, and the composition and doses are not always clearly reported. A few studies reported no effects, but none reported problems connected to milk thistle administration. However, the overall picture shows that the use of milk thistle results in improved or restored health parameters or better animal performance.

Key words

Silybum marianum - Asteraceae - silymarin - nutraceuticals - hepatoprotector - animal health


Publication History

Received: 10 May 2022

Accepted after revision: 05 September 2022

Accepted Manuscript online:
27 October 2022

Article published online:
10 January 2023

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Karkanis A, Bilalis D, Efthimiadou A. Cultivation of milk thistle (Silybum marianum L. Gaertn.), a medicinal weed. Ind Crops Prod 2011; 34: 825-830
    CrossrefPubMedGoogle Scholar
  • 2 Martinelli T, Potenza E, Moschella A, Zaccheria F, Benedettelli S, Andrzejewska J. Phenotypic evaluation of a milk thistle germplasm collection: Fruit morphology and chemical composition. Crop Sci 2016; 56: 3160-3172
    CrossrefPubMedGoogle Scholar
  • 3 Martinelli T, Fulvio F, Pietrella M, Focacci M, Lauria M, Paris R. In Silybum marianum Italian wild populations the variability of silymarin profiles results from the combination of only two stable chemotypes. Fitoterapia 2021; 148: 104797
    CrossrefPubMedGoogle Scholar
  • 4 European Medicines Agency. Assessment report on Silybum marianum (L.) Gaertn., fructus. Comm Herb Med Prod EMA/HMPC/294188/2013 2018; 44: 78
    PubMedGoogle Scholar
  • 5 Franz Ch, Bauer R, Carle R, Tedesco D, Tubaro A, Zitterl-Eglseer K. Study on the assessment of plants/herbs, plant/herb extracts and their naturally or synthetically produced components as ‘additives’ for use in animal production. EFSA Supporting Pubblications 2007; 4: 070828
    PubMedGoogle Scholar
  • 6 Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-143
    CrossrefPubMedGoogle Scholar
  • 7 Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Complement Med Res 2007; 14: 70-80
    CrossrefPubMedGoogle Scholar
  • 8 European Pharmacopoeia 9th ed. Milk Thistle Fruit. Council of Europe; 1860
    Google Scholar
  • 9 Gillessen A, Schmidt HHJ. Silymarin as supportive treatment in liver diseases: A narrative review. Adv Ther 2020; 37: 1279-1301
    CrossrefPubMedGoogle Scholar
  • 10 Ferenci P. Silymarin in the treatment of liver diseases: What is the clinical evidence? Silymarin in the treatment of liver diseases. Clin Liver Dis 2016; 7: 8-10
    CrossrefPubMedGoogle Scholar
  • 11 Di Costanzo A, Angelico R. Formulation strategies for enhancing the bioavailability of silymarin: The state of the art. Molecules 2019; 24: 2155
    CrossrefPubMedGoogle Scholar
  • 12 Morazzoni P, Magistretti MJ, Giachetti C, Zanolo G. Comparative bioavailability of silipide, a new flavanolignan complex, in rats. Eur J Drug Metab Pharmacokinet 1992; 17: 39-44
    CrossrefPubMedGoogle Scholar
  • 13 Wang Y, Zhang D, Liu Z, Liu G, Duan C, Jia L, Feng F, Zhang X, Shi Y, Zhang Q. In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery. Nanotechnology 2010; 21: 155104
    CrossrefPubMedGoogle Scholar
  • 14 Cao X, Deng W, Fu M, Zhu Y, Liu H, Wang L, Zeng J, Wei Y, Xu X, Yu J. Seventy-two-hour release formulation of the poorly soluble drug silybin based on porous silica nanoparticles: In vitro release kinetics and in vitro/in vivo correlations in beagle dogs. Eur J Pharm Sci 2013; 48: 64-71
    CrossrefPubMedGoogle Scholar
  • 15 Yan-Yu X, Yun-Mei S, Zhi-Peng C, Qi-Neng P. Preparation of silymarin proliposome: A new way to increase oral bioavailability of silymarin in beagle dogs. Int J Pharm 2006; 319: 162-168
    CrossrefPubMedGoogle Scholar
  • 16 Yu J, Zhu Y, Wang L, Peng M, Tong S, Cao X, Qiu H, Xu X. Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol Sin 2010; 31: 759-764
    CrossrefPubMedGoogle Scholar
  • 17 Zhang Q, Ahn JM, Kim IH. Micelle silymarin supplementation to sowsʼ diet from day 109 of gestation to entire lactation period enhances reproductive performance and affects serum hormones and metabolites. J Anim Sci 2021; 99: skab354
    CrossrefPubMedGoogle Scholar
  • 18 Kosina P, Ken V, Gebhardt R, Grambal F, Ulrichová J, Walterová D. Antioxidant properties of silybin glycosides. Phytother Res 2002; 16: 33-39
    CrossrefPubMedGoogle Scholar
  • 19 Filburn CR, Kettenacker R, Griffin DW. Bioavailability of a silybin phosphatidylcholine complex in dogs. J Vet Pharmacol Ther 2007; 30: 132-138
    CrossrefPubMedGoogle Scholar
  • 20 Tvrdý V, Pourová J, Jirkovský E, Křen V, Valentová K, Mladěnka P. Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin. Med Res Rev 2021; 41: 2195-2246
    CrossrefPubMedGoogle Scholar
  • 21 Wu JW, Lin LC, Hung SC, Chi CW, Tsai TH. Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application. J Pharm Biomed Anal 2007; 45: 635-641
    CrossrefPubMedGoogle Scholar
  • 22 Webb CB, Gustafson DL, Twedt DC. Bioavailability following oral administration of a silibinin-phosphatidylcholine complex in cats. Intern J Appl Res Vet Med 2012; 10: 107-112
    PubMedGoogle Scholar
  • 23 Hackett SE, Mama RK, Twedt CD, Gustafson DL. Pharmacokinetics and safety of silibinin in horses. Am J Vet Res 2013; 74: 1327-1332
    CrossrefPubMedGoogle Scholar
  • 24 Wu JW, Lin LC, Tsai TH. Drug–drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 2009; 121: 185-193
    CrossrefPubMedGoogle Scholar
  • 25 Tedesco DEA, Cagnardi P. Regulatory Guidelines for Nutraceuticals in the European Union. In: Gupta RC, Srivastava A, Lall R. eds. Nutraceuticals in Veterinary Medicine. Cham: Springer International Publishing; 2019: 793-805
    Google Scholar
  • 26 European Parliament and the Council of the European Union. Regulation (EC) No 1831/2003. Off J Eur Union 2003; 4: 29-43
    PubMedGoogle Scholar
  • 27 European Parliament and the Council of the European Union. No 68/2013 of 16 January 2013 on the Catalogue of feed materials. OJ L 29, 30.1.2013, p. 1–6. Off J Eur Union 2013; 1-64
    PubMedGoogle Scholar
  • 28 European Parliament and the Council of the European Union. Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC. Off J Eur Union 2019; L4: 43-167
    PubMedGoogle Scholar
  • 29 Drackley KJ. Biology of dairy cows during the transition period: The final frontier?. J Dairy Sci 1999; 82: 2259-2273
    CrossrefPubMedGoogle Scholar
  • 30 Bertics SJ, Grummer RR, Cadorniga-Valino C, Stoddard EE. Effects of prepartum dry matter intake on liver triglyceride concentration and early lactation. J Dairy Sci 1992; 75: 1914-1922
    CrossrefPubMedGoogle Scholar
  • 31 Gerloff BJ, Herdt TH, Emery RS. Relationship of hepatic lipidosis to health and performance in dairy cattle. J Am Vet Med Assoc 1986; 188: 845-850
    PubMedGoogle Scholar
  • 32 Tedesco D. The potentiality of herbs and plant extracts as feed additive in livestock production. Zootec Nutr Anim 2001; 3 – 4: 111-133
    PubMedGoogle Scholar
  • 33 Tedesco D, Tava A, Galletti S, Tamei M, Varisco G, Costa A, Steindler S. Effects of silymarin, a natural hepatoprotector, in periparturient dairy cows. J Dairy Sci 2004; 87: 2239-2247
    CrossrefPubMedGoogle Scholar
  • 34 Galletti S. In vitro and in vivo approaches for the assessment of safety and efficacy of plants and plants extracts as feed additives [PhD Thesis]. Milan: Veterinary Medicine, University of Milan; 2006
    Google Scholar
  • 35 Křížová L, Watzková J, Třináctý J, Richter M, Buchta M. Rumen degradability and whole tract digestibility of flavonolignans from milk thistle (Silybum marianum) fruit expeller in dairy cows. Czech J Anim Sci 2011; 56: 269-278
    CrossrefPubMedGoogle Scholar
  • 36 Tedesco D, Domeneghini C, Sciannimanico D, Tameni M, Steindler S, Galletti S. Silymarin, a possible hepatoprotector in dairy cows: Biochemical and histological observations. J Vet Med Series A 2004; 51: 85-89
    CrossrefPubMedGoogle Scholar
  • 37 Ulger I, Onmaz AC, Ayaşan T. Effects of silymarin (Silybum marianum) supplementation on milk and blood parameters of dairy cattle. SA J An Sci 2017; 47: 758
    CrossrefPubMedGoogle Scholar
  • 38 Tedesco D, Galletti S, Rossetti S, Turini J, Varisco G. Silymarin administration to periparturient dairy goats: effects on milk production and quality. J Dairy Sci 2004; 87 (Suppl. 01) 392
    PubMedGoogle Scholar
  • 39 Spagnuolo MS, Abrescia P, Carlucci A, Tedesco D, Galletti S, Ferrara L. Effect of Silymarin Administration on Plasma And Milk Redox Status In Periparturient Dairy Goats. In: Bullitta S, ed. Bioactive Compounds in Pasture Species for Phytotherapy and Animal Welfare Sassari, Italy: Digita Space Press; 2005: 87-95
    Google Scholar
  • 40 Tedesco D, Galletti S, Olivero D, Tameni M, Rossetti S. Silymarin administration to transition dairy goats: Effects on liver tissue and plasma metabolites. J Dairy Sci 2004; 87 (Suppl. 01) 355
    PubMedGoogle Scholar
  • 41 Tedesco D, Turini J, Galletti S. Effects of silymarin administration to middle-lactating dairy goats. In: European Federation of Animal Science. Book of Abstracts of the 56th Annual Meeting of the European Association for Animal Production, Uppsala, Sweden: 2005: 165 Accessed December 14, 2022 at: https://www.wageningenacademic.com/pb-assets/wagen/files/e-books/open_access/9789086865444eaap2005-e-1430309765397.pdf
    Google Scholar
  • 42 Vojtísek B, Hronová B, Hamrík J, Janková B. Milk thistle (Silybum marianum, L., Gaertn.) in the feed of ketotic cows. Vet Med (Praha) 1991; 36: 321-330
    PubMedGoogle Scholar
  • 43 Kim DH, Kim KH, Nam IS, Lee SS, Choi CW, Kim WY, Kwon EG, Lee KY, Lee MJ, Oh YK. Effect of indigenous herbs of growth, blood metabolites and carcass characteristics in the late fattening period of hanwoo steers. Asian Australas J Anim Sci 2013; 34: 7-9
    PubMedGoogle Scholar
  • 44 Dehghan A, Rowshan-Ghasrodashti A, Esfandiari A, Mohebbi-Fani M, Bagher Hoshyar M, Nayeri K. Hepatoprotective effect of silymarin during negative energy balance in sheep. Comp Clin Pathol 2011; 20: 233-238
    CrossrefPubMedGoogle Scholar
  • 45 Mashayekhi M. Renoprotective effect of silymarin on gentamicininduced nephropathy. Afr J Pharm Pharmacol 2012; 6: 2241-2246
    PubMedGoogle Scholar
  • 46 Tian MY, Fan JH, Zhuang ZW, Dai F, Wang CY, Hou HT, Ma YZ. Effects of silymarin on p65 NF-κB, p38 MAPK and CYP450 in LPS-induced hoof dermal inflammatory cells of dairy cows. BMC Vet Res 2019; 15: 127
    CrossrefPubMedGoogle Scholar
  • 47 Zheng XC, Wu QJ, Song ZH, Zhang H, Zhang JF, Zhang LL, Zhang TY, Wang C, Wang T. Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide. Poultry Sciences 2016; 95: 2281-2289
    CrossrefPubMedGoogle Scholar
  • 48 Peng G, Huang E, Ruan J, Huang L, Liang H, Wei Q, Xie X, Zeng Q, Huang J. Effects of a high energy and low protein diet on hepatic and plasma characteristics and Cidea and Cidec mRNA expression in liver and adipose tissue of laying hens with fatty liver hemorrhagic syndrome. Anim Sci J 2019; 90: 247-254
    CrossrefPubMedGoogle Scholar
  • 49 Jahanian E, Mahdavi HA, Jahanian R. Silymarin improved the growth performance via modulating the microbiota and mucosal immunity in Escherichia coli-challenged broiler chicks. Livest Sci 2021; 249: 104529
    CrossrefPubMedGoogle Scholar
  • 50 Elnaggar SA, Reham AMA, El-Said EM. Physiological and immunological responses of ducks (Cairina moschata domestica) to Silymarin supplementation. Egypt. Poult Sci 2020; 40: 895-913
    PubMedGoogle Scholar
  • 51 Shahsavan M, Salari S, Ghorbani M. Effect of dietary inclusion of Silybum marianum oil extraction byproduct on growth performance, immune response and cecal microbial population of broiler chicken. Biotechnol Anim Husb 2021; 37: 45-64
    CrossrefPubMedGoogle Scholar
  • 52 Hashemi Jabali NS, Mahdavi AH, Ansari Mahyari S, Sedghi M, Akbari MKR. Effects of milk thistle meal on performance, ileal bacterial enumeration, jejunal morphology and blood lipid peroxidation in laying hens fed diets with different levels of metabolizable energy. J Anim Physiol Anim Nutr 2018; 102: 410-420
    CrossrefPubMedGoogle Scholar
  • 53 Faryadi S, Sheikhahmadi A, Farhadi A, Nourbakhsh H. Effects of silymarin and nano-silymarin on performance, egg quality, nutrient digestibility, and intestinal morphology of laying hens during storage. Ital J Anim Sci 2021; 20: 1633-1644
    CrossrefPubMedGoogle Scholar
  • 54 Gholamalian R, Mahdavi HA, Riasi A. Hepatic fatty acids profile, oxidative stability and egg quality traits ameliorated by supplementation of alternative lipid sources and milk thistle meal. J Anim Physiol Anim Nutr 2021; 106: 860-871
    CrossrefPubMedGoogle Scholar
  • 55 Šťastník O, Mrkvicová E, Pavlata L, Roztočilová A, Umlášková B, Anzenbacherová E. Performance, biochemical profile and antioxidant activity of hens supplemented with addition of milk thistle (Silybum marianum) seed cakes in diet. Acta Univ Agric Silvic Mendelianae Brun 2019; 67: 993-1003
    CrossrefPubMedGoogle Scholar
  • 56 Erişir Z, Mutlu Sİ, Şimşek ÜG, Çiftçi M, Azman MA, Benzer F, Erişir M. Yüksek Kalorili Bıldırcın Karma Yemlerine Deve Dikeni (Silybum marianum) Tohumu İlavesinin Yumurta Verimi, Yumurta Kalite Özellikleri, Kuluçka Randımanı ve Oksidatif Stres Parametreleri Üzerine Etkisi. Kafkas Univ Vet Fak Derg 2016; 22: 577-584
    PubMedGoogle Scholar
  • 57 Lukanov H, Pavlova I, Ivanov V, Slavov T, Petrova Y, Bozakova NA. Effect of silymarin supplementation on some productive and hematological parameters in meat type male Japanese quails. Emir J Food Agric 2018; 30: 984-989
    PubMedGoogle Scholar
  • 58 Schiavone A, Righi F, Quarantelli A, Bruni R, Serventi P, Fusari A. Use of Silybum marianum fruit extract in broiler chicken nutrition: influence on performance and meat quality. J Anim Physiol Anim Nutr 2007; 91: 256-262
    CrossrefPubMedGoogle Scholar
  • 59 Šťastník O, Jůzl M, Karásek F, Štenclová H, Nedomová S, Pavlata L, Mrkvicová E, Doležal P, Jarošová A. The effect of feeding milk thistle seed cakes on quality indicators of broiler chickens meat. Potr S J F Sci 2016; 10: 248-254
    CrossrefPubMedGoogle Scholar
  • 60 Janocha A, Milczarek A, Pietrusiak D. Impact of milk thistle (Silybum marianum [L.] Gaertn.) seeds in broiler chicken diets on rearing results, carcass composition, and meat quality. Animals 2021; 11: 1550
    CrossrefPubMedGoogle Scholar
  • 61 Rashidi N, Bujarpoor M, Chaji M, Aghaei A. Effect of Silybum marianum seed on performance, carcass characteristics and blood parameters of broiler chickens. Anim Prod Res 2015; 3: 11-21
    PubMedGoogle Scholar
  • 62 Gawel A, Kotonski B, Madej JA, Mazurkiewicz M. Effect of silymarin on chicken and turkey broilersʼ rearing and the production indices of reproduction hen flocks. Med Weter 2003; 59: 517-520
    PubMedGoogle Scholar
  • 63 Suchý P, Straková E, Kummer V, Herzig I, Písaříková V, Blechová R, Mašková J. Hepatoprotective effects of milk thistle (Silybum marianum) seed cakes during the chicken broiler fattening. Acta Vet Brno 2008; 77: 31-38
    CrossrefPubMedGoogle Scholar
  • 64 Gharahveysi S. Milk thistle protective effect on liver and kidney of broiler chickens. Agr Nat Resour 2019; 53: 429-432
    PubMedGoogle Scholar
  • 65 Bagno O, Shevchenko S, Shevchenko A, Prokhorov O, Shentseva A, Vavin G, Ulrich E. Physiological status of broiler chickens with diets supplemented with milk thistle extract. Vet World 2021; 14: 1319-1323
    CrossrefPubMedGoogle Scholar
  • 66 Zarei A, Morovat M, Chamani M, Sadeghi AA, Dadvar P. Effect of in ovo feeding and dietary feeding of Silybum marianum extract on performance, immunity and blood cation-anion balance of broiler chickens exposed to high temperatures. Iran J Appl Anim Sci 2016; 6: 697-705
    PubMedGoogle Scholar
  • 67 Abdalla AA, Abou-Shehema BM, Hamed RS, El-deken RM. Effect of silymarin supplementation on the performance of developed chickens under summer conditions 1-during growth period. Egypt Poult Sci 2018; 38: 305-329
    PubMedGoogle Scholar
  • 68 Sultan A, Ahmad S, Khan S, Chand N, Tahir M, Shakoor A. Comparative effect of zinc oxide and silymarin on growth, nutrient utilization and hematological parameters of heat distressed broiler. Pakistan J Zool 2018; 50: 751-756
    CrossrefPubMedGoogle Scholar
  • 69 Ahmad M, Chand N, Rifat UK, Ahmad N, Khattak I, Naz S. Dietary supplementation of milk thistle (Silybum marianum): growth performance, oxidative stress, and immune response in natural summer stressed broilers. Trop Anim Health Prod 2020; 52: 711-715
    CrossrefPubMedGoogle Scholar
  • 70 Baradaran A, Samadia F, Ramezanpour SS, Yousefdousta S. Hepatoprotective effects of silymarin on CCl4-induced hepatic damage in broiler chickens model. Toxicol Rep 2019; 6: 788-794
    CrossrefPubMedGoogle Scholar
  • 71 Kamali M, Mostafaei SA. Hepatoprotective effect of Silybum marianum on experimental hepatotoxicity in broilers. Comp Clin Pathol 2014; 23: 967-973
    CrossrefPubMedGoogle Scholar
  • 72 Behboodi HR, Samadi F, Shams SM, Gangi F, Samadi S. Effects of silymarin on growth performance, internal organs and some blood parameters in Japanese quail subjected to oxidative stress induced by carbon tetrachloride. Poultry Science Journal 2017; 5: 31-40
    PubMedGoogle Scholar
  • 73 Yi D, Wang C, Sun D, Hou Y, Ding B, Wang L, Gong J. Diet supplementation of silymarin increased the antioxidantive capacity in cumene hydroperoxide-challenged ducks. J Anim Vet Adv 2012; 11: 2986-2994
    CrossrefPubMedGoogle Scholar
  • 74 Radko L, Cybulski W. The decrease of lasalocid residue in the edible tissues by silymarin supplementation of chicken diet. Food Addit Contam – Chem Ana 2019; 36: 722-728
    CrossrefPubMedGoogle Scholar
  • 75 Clauss M, Hatt JM. Evidence-based rabbit housing and nutrition. Vet Clin North Am Exot Anim Pract 2017; 20: 871-884
    CrossrefPubMedGoogle Scholar
  • 76 Crowell-Davis S. Rabbit Behavior. Vet Clin North Am Exot Anim Pract 2021; 24: 53-62
    CrossrefPubMedGoogle Scholar
  • 77 Kosina P, Dokoupilová A, Janda K, Grambal F, Ulrichová J, Walterova D. Effect of Silybum marianum fruit constituents on the health status of rabbits in repeated 42-day fattening experiment. Anim Feed Sci Technol 2017; 223: 128-140
    CrossrefPubMedGoogle Scholar
  • 78 Carabano R, Badiola I, Chamorro S, García J, García-Ruiz AI, García-Rebollar P, Gómez-Conde MS, Gutiérrez I, Nicodemus N, Villamide MJ, de Blas JC. New trends in rabbit feeding: Influence of nutrition on intestinal health. Span J Agric Res 2008; 6: 15-25
    CrossrefPubMedGoogle Scholar
  • 79 Attia AY, Hamed SR, Bovera F, Abd El-Hamid AEE, Al-Harthi MA, Shahba HA. Semen quality, antioxidant status and reproductive performance of rabbits bucks fed milk thistle seeds and rosemary leaves. Anim Reprod Sci 2017; 184: 178-186
    CrossrefPubMedGoogle Scholar
  • 80 Cullere M, Dalle Zotte A, Celia C, Renteria-Monterrubio AL, Gerencsér ZS, Szendrő ZS, Kovács M, Kachlek ML, Matics ZS. Effect of Silybum marianum herb on the productive performance, carcass traits and meat quality of growing rabbits. Livest Sci 2016; 194: 31-36
    CrossrefPubMedGoogle Scholar
  • 81 Pebriansyah A, Lukešová D, Knížková I, Siberová P, Kunc P. The effect of natural phytoadditive Silybum marianum on performance of broiler rabbits. Sci Agric Bohem 2019; 50: 40-45
    PubMedGoogle Scholar
  • 82 Aboelhadid MS, El-Ashramb S, Hassan KM, Arafa WM, BahaaEldin DA. Hepato-protective effect of curcumin and silymarin against Eimeria stiedae in experimentally infected rabbits. Livest Sci 2019; 221: 33-38
    CrossrefPubMedGoogle Scholar
  • 83 Jahan S, Khan M, Imran S, Sair M. The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits. J Pak Med Assoc 2015; 65: 620-622
    PubMedGoogle Scholar
  • 84 Grela ER, Świątkiewicz M, Florek M, Wojtaszewska I. Impact of milk thistle (Silybum marianum L.) seeds in fattener diets on pig performance and carcass traits and fatty acid profile and cholesterol of meat, backfat and liver. Livest Sci 2020; 239: 104180
    CrossrefPubMedGoogle Scholar
  • 85 Jiang X, Lin S, Lin Y, Fang Z, Xu S, Feng B, Zhuo Y, Li J, Che L, Jiang X, Wu D. Effects of silymarin supplementation during transition and lactation on reproductive performance, milk composition and haematological parameters in sows. J Anim Physiol Anim Nutr 2020; 104: 1896-1903
    CrossrefPubMedGoogle Scholar
  • 86 Farmer C, Lapointe J, Palin MF. Effects of the plant extract silymarin on prolactin concentrations, mammary gland development, and oxidative stress in gestating gilts. J Anim Sci 2014; 92: 2922-2930
    CrossrefPubMedGoogle Scholar
  • 87 Farmer C, Lapointe J, Cormier I. Providing the plant extract silymarin to lactating sows: effects on litter performance and oxidative stress in sows. Animal 2017; 11: 405-410
    CrossrefPubMedGoogle Scholar
  • 88 Loisel F, Quesnel H, Farmer C. Short Communication: Effect of silymarin (Silybum marianum) treatment on prolactin concentrations in cyclic sows. Can J Anim Sci 2013; 93: 227-230
    CrossrefPubMedGoogle Scholar
  • 89 Koo HD, Zhang Q, Sampath V, Kim I. Effect of micelle silymarin supplementation on the growth performance, nutrient digestibility, fecal microbiome, gas emissions, blood profile, meat quality, and antioxidant property in finishing pigs. J Anim Sci 2022; 100: 150-151
    CrossrefPubMedGoogle Scholar
  • 90 Banaee M, Sureda A, Mirvaghefi AR, Rafei GR. Effects of long-term silymarin oral supplementation on the blood biochemical profile of rainbow trout (Oncorhynchus mykiss). Fish Physiol Biochem 2011; 37: 885-896
    CrossrefPubMedGoogle Scholar
  • 91 Ahmadi K, Banaee M, Vosoghei AR, Mirvaghefei AR, Ataeimehr B. Evaluation of the immunomodulatory effects of silymarin extract (Silybum marianum) on some immune parameters of rainbow trout, Oncorhynchus mykiss (actinopterygii: salmoniformes: salmonidae). Acta Icth et Piscat 2012; 42: 113-120
    CrossrefPubMedGoogle Scholar
  • 92 El-Houseiny W, Abd El-Hakim YM, Metwally MMM, Abdel-Ghfar SS, Khalil AA. The single or combined Silybum marianum and co-enzyme Q10 role in alleviating fluoride-induced impaired growth, immune suppression, oxidative stress, histological alterations, and reduced resistance to Aeromonas sobria in African catfish (Clarias gariepinus). Aquaculture 2022; 548: 737693
    CrossrefPubMedGoogle Scholar
  • 93 Hassaan MS, Mohammady EY, Soaudy MR, El-Garhy ASH, Mahmoud MAM, Shereen AM, El-Haroun RE. Effect of Silybum marianum seeds as a feed additive on growth performance, serum biochemical indices, antioxidant status, and gene expression of Nile tilapia, Oreochromis niloticus (L.) fingerlings. Aquaculture 2019; 509: 178-187
    CrossrefPubMedGoogle Scholar
  • 94 Owatari MS, Alves Jesus GF, Brum A, Pereira SA, Lehmann NB, de Pádua Pereira U, Martins ML, Pedreira Mouriño JL. Sylimarin as hepatic protector and immunomodulator in Nile tilapia during Streptococcus agalactiae infection. Fish Shellfish Immunol 2018; 82: 565-572
    CrossrefPubMedGoogle Scholar
  • 95 Wang J, Zhou H, Wang X, Mai K, He G. Effects of silymarin on growth performance, antioxidant capacity and immune response in turbot (Scophthalmus maximus L.). J World Aquacult Soc 2019; 50: 1168-1181
    CrossrefPubMedGoogle Scholar
  • 96 Xiao P, Ji H, Ye Y, Zhang B, Chen Y, Tian J, Liu P, Chen L, Du Z. Dietary silymarin supplementation promotes growth performance and improves lipid metabolism and health status in grass carp (Ctenopharyngodon idellus) fed diets with elevated lipid levels. Fish Physiol Biochem 2017; 43: 245-263
    CrossrefPubMedGoogle Scholar
  • 97 Wei L, Wu P, Zhou XQ, Jiang WD, Liu Y, Kuang SY, Tang L, Feng L. Dietary silymarin supplementation enhanced growth performance and improved intestinal apical junctional complex on juvenile grass carp (Ctenopharyngodon idella). Aquaculture 2020; 525: 735311
    CrossrefPubMedGoogle Scholar
  • 98 Colitti M, Grasso S. Nutraceuticals and regulation of adipocyte life: Premises or promises. Biofactors 2014; 40: 398-418
    CrossrefPubMedGoogle Scholar
  • 99 Marchegiani A, Fruganti A, Gavazza A, Mangiaterra S, Candellone A, Fusi E, Rossi G, Cerquetella M. Evidences on Molecules Most Frequently Included in Canine and Feline Complementary Feed to Support Liver Function. Vet Med Int 2020; 2020: 1-7
    CrossrefPubMedGoogle Scholar
  • 100 Vandeweerd JM, Cambier C, Gustin P. Nutraceuticals for Canine Liver Disease. Vet Clin North Am Small Anim Pract 2013; 43: 1171-1179
    CrossrefPubMedGoogle Scholar
  • 101 Gogulski M, Ardois M, Grabska J, Libera K, Szumacher-Strabel M, Cieślak A, Strompfová V. Dietary supplements containing silymarin as a supportive factor in the treatment of canine hepatopathies. Med Weter 2020; 76: 700-708
    PubMedGoogle Scholar
  • 102 Sgorlon S, Stefanon B, Sandri M, Colitti M. Nutrigenomic activity of plant derived compounds in health and disease: Results of a dietary intervention study in dog. Res Vet Sci 2016; 109: 142-148
    CrossrefPubMedGoogle Scholar
  • 103 Gogulski M, Cieślak A, Grabska J, Ardois M, Pomorska-Mól M, Kołodziejski PA, Libera K, Strompfová V, Szumacher-Strabel M. Effects of silybin supplementation on nutrient digestibility, hematological parameters, liver function indices, and liver-specific mi-RNA concentration in dogs. BMC Vet Res 2021; 17: 228
    CrossrefPubMedGoogle Scholar
  • 104 Paulova J, Dvorak M, Kolouch F, Vánová L, Janecková L. Verification of the hepatoprotective and therapeutic effect of silymarin in experimental liver injury with tetrachloromethane in dogs. Vet Med (Praha) 1990; 35: 629-635
    PubMedGoogle Scholar
  • 105 Skorupski KA, Hammond GM, Irish AM, Kent MS, Guerrero TA, Rodriguez CO, Griffin DW. Prospective randomized clinical trial assessing the efficacy of denamarin for prevention of ccnu-induced hepatopathy in tumor-bearing dogs: Hepatoprotection for CCNU. J Vet Intern Med 2011; 25: 838-845
    CrossrefPubMedGoogle Scholar
  • 106 Kocatürk M, Inan OE, Levent P, Yilmaz Z. Protective effects of S-adenosylmethionine (SAMe) and silybin on hepatorenal and hemostatic functions in dogs with endotoxemia. Turkish J Vet Anim Sci 2016; 40: 788-796
    CrossrefPubMedGoogle Scholar
  • 107 Soltanian A, Mosallanejad B, Jalali MR, Varzi NH, Ghorbanpour M. Comparative evaluation of therapeutic effects of silymarin and hydrocortisone on clinical and hematological alterations, and organ injury (liver and heart) in a low-dose canine lipopolysaccharide-induced sepsis model. Vet Res Forum 2020; 11: 235-241
    PubMedGoogle Scholar
  • 108 Varzi HN, Esmailzadeh S, Morovvati H, Avizeh R, Shahriari A, Givi ME. Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. J Vet Pharmacol Ther 2007; 30: 477-481
    CrossrefPubMedGoogle Scholar
  • 109 Mosallanejad B, Avizeh R, Varzi NH. Succesful treatment of Stanozolol induced-hepatotoxicity with Silymarin in a bitch. Asian J Anim Sci 2011; 5: 213-218
    CrossrefPubMedGoogle Scholar
  • 110 Mosallanejad B, Razi Jalali M, Avizeh R, Pourmahdi M. Evaluation of prophylactic and therapeutic effects of silymarin on phenobarbital–induced hepatoxicity in cats. Iran J Vet Med 2020; 14: 205-214
    PubMedGoogle Scholar
  • 111 Mosallanejad B, Avizeh R, Varzi NH, Pourmahdi M. Evaluation of prophylactic and therapeutic effects of silymarin on acute toxicity due to tetracycline severe overdose in cats: a preliminary study. Iran J Vet Res 2012; 13: 38
    PubMedGoogle Scholar
  • 112 Mosallanejad B, Avizeh R, Varzi NH, Pourmahdi M. Evaluation of prophylactic and therapeutic effects of silymarin on mebendazole-induced hepatotoxicity in cats. Comp Clin Path 2012; 21: 681-685
    CrossrefPubMedGoogle Scholar
  • 113 Avizeh R, Najafzadeh H, Jalali MR, Shirali S. Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats. J Vet Pharmacol Ther 2010; 33: 95-99
    CrossrefPubMedGoogle Scholar
  • 114 Vereckei A, Besch HR, Zipes DP. Combined amiodarone and silymarin treatment, but not amiodarone alone, prevents sustained atrial flutter in dogs. J Cardiovasc Electrophysiol 2003; 14: 861-867
    CrossrefPubMedGoogle Scholar
  • 115 Webb CB, McCord KW, Twedt DC. Assessment of oxidative stress in leukocytes and granulocyte function following oral administration of a silibinin-phosphatidylcholine complex in cats. Am J Vet Res 2009; 70: 57-62
    CrossrefPubMedGoogle Scholar
  • 116 Au AY, Hasenwinkel JM, Frondoza CG. Silybin inhibits interleukin-1β-induced production of pro-inflammatory mediators in canine hepatocyte cultures: Silybin inhibits pro-inflammatory mediators in canine hepatocytes. J Vet Pharmacol Ther 2011; 34: 120-129
    CrossrefPubMedGoogle Scholar
  • 117 Au AY, Hasenwinkel JM, Frondoza CG. Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro: Hepatoprotective effects of S-adenosylmethionine and silybin. J Anim Physiol Anim Nutr (Berl) 2013; 97: 331-341
    CrossrefPubMedGoogle Scholar
  • 118 Dockalova H, Zeman L, Baholet D, Batik A, Skalickova S, Horky P. Dose effect of milk thistle (Silybum marianum) seed cakes on the digestibility of nutrients, flavonolignans and the individual components of the silymarin complex in horses. Animals 2021; 11: 1687
    CrossrefPubMedGoogle Scholar
  • 119 Dockalova H, Zeman L, Horky P. Influence of milk thistle (Silybum marianum) seed cakes on biochemical values of equine plasma subjected to physical exertion. Animals 2021; 11: 1-16
    CrossrefPubMedGoogle Scholar
  • 120 de la Rebiere de Pouyade G. Serteyn D. The role of activated neutrophils in the early stage of equine laminitis. Vet J 2011; 189: 27-33
    CrossrefPubMedGoogle Scholar
  • 121 Taylor S. A review of equine sepsis. Equine Vet Educ 2015; 27: 99-109
    CrossrefPubMedGoogle Scholar
  • 122 Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro . Toxins (Basel) 2014; 6: 2962-2974
    CrossrefPubMedGoogle Scholar
  • 123 Zholobenko A, Mouithys-Mickalad M, Modriansky D, Serteyn D, Franck T. Polyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity. J Vet Pharmacol Therap 2016; 39: 592-601
    CrossrefPubMedGoogle Scholar
  • 124 Gugliandolo E, Crupi R, Biondi V, Licata P, Cuzzocrea S, Passantino A. Protective effect of silibinin on lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells, an in vitro study. Animals 2020; 10: 2022
    CrossrefPubMedGoogle Scholar