Skip to main content
Log in

Effects of long-term silymarin oral supplementation on the blood biochemical profile of rainbow trout (Oncorhynchus mykiss)

  • Published:
Fish Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Silymarin, an extract from “milk thistle” (Silybum marianum) plant is traditionally used as herbal medicine. The present study was conducted to investigate the clinical effects and possible side effects of silymarin on biochemical blood parameters of rainbow trout (Oncorhynchus mykiss). Fishes were treated with 0 (control), 100, 400, and 800 mg of silymarin per kg of food during 4 weeks. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine kinase (CK), glucose, total protein, creatinine, triglyceride, cholesterol, urea, uric acid and liver cellular total antioxidant, and protein content were measured after 7, 14, and 28 days of silymarin treatment. The results showed that oral administration of silymarin in fish significantly reduced plasma glucose and cholesterol levels and relatively increased plasma total protein and globulin concentrations (P < 0.05). Increasing plasma albumin levels indicate the important role of albumin in drug transportation in circulatory system of fish. Silymarin also stabilized cellular membrane structure and regulated the levels of AST, ALT, ALP, CK, and LDH activity. In conclusion, on the basis of these results, oral administration of silymarin up to 400 mg per 1 kg of food has no side effect on blood biochemical and clinical parameters of fishes. However, oral administration of 800 mg/kg- of silymarin caused cytotoxicity and modifications in blood biochemical parameters of fish.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alqasoumi SI, Al-Howiriny TA, Abdel-Kaer MS (2008) Evaluation of the hepatoprotective effect of Aloe vera, Clematis hirsute and bee propolis against experimentally induced liver injury in rats. Int J Pharmacol 4(3):213–217

    Article  Google Scholar 

  • Banaee M (2010) Influence of silymarin in decline of sub-lethal diazinon-induced oxidative stress in rainbow trout (Oncorhynchus mykiss). Ph.D. Thesis, Aquaculture and Environmental Department, Natural Resource Faculty, Natural Resource and Agriculture Collage, Tehran University, Iran, 149 pp

  • Basiglio CL, Sánchez Pozzi EJ, Mottino AD, Roma MG (2009) Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chemico-Biological Interact 179:297–303. doi:10.1016/j.cbi.2008.12.008

    Article  CAS  Google Scholar 

  • Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, Böcker RH, Beckurts KT, Lang W, Hunz M, Fuhr U (2000) Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 86(6):250–256. doi:10.1111/j.0901-9928.2000.860602.x

    Article  PubMed  CAS  Google Scholar 

  • Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F (2001) Silybin, a new iron-chelating agent. J Inorg Biochem 85:123–129

    Article  PubMed  CAS  Google Scholar 

  • Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T, Uslu S, Demirustu C, Aral E, Can Baser KH (2008) Effects of carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine 15(6–7):447–452. doi:10.1016/j.phymed.2007.11.022

    Article  PubMed  CAS  Google Scholar 

  • Christybapita D, Divyagnaneswari M, Dinakaran Michael R (2007) Oral administration of Eclipta alba leaf aqueous extract enhances the non-specific immune responses and disease resistance of Oreochromis mossambicus. Fish Shellfish Immunol 23:840–852. doi:10.1016/j.fsi.2007.03.010

    Article  PubMed  CAS  Google Scholar 

  • Citarasu T, Sivaram V, Immanuel G, Rout N, Murugan V (2006) Influence of selected Indian immunostimulant herbs against white spot syndrome virus (WSSV) infection in black tiger shrimp, Penaeus monodon with reference to haematological, biochemical and immunological changes. Fish Shellfish Immunol 21:372–384. doi:10.1016/j.fsi.2006.01.002

    Article  PubMed  Google Scholar 

  • D’Andrea V, Perez LM, Pozzi EJS (2005) Inhibition of rat liver UDP-glucuronosyltransferase by silymarin and the metabolite silibinin-glucuronide. Life Sci 77:683–692. doi:10.1016/j.lfs.2005.01.011

    Article  PubMed  Google Scholar 

  • Divyagnaneswari M, Christybapita D, Dinakaran Michael R (2007) Enhancement of nonspecific immunity and disease resistance in Oreochromis mossambicus by Solanum trilobatum leaf fractions. Fish Shellfish Immunol 23:249–259. doi:10.1016/j.fsi.2006.09.015

    Article  PubMed  CAS  Google Scholar 

  • Dügenci SK, Arda N, Candan A (2003) Some medicinal plants as immunostimulant for fish. J Ethnopharmacol 88:99–106. doi:10.1016/S0378-8741(03)00182-X

    Article  PubMed  Google Scholar 

  • El-Kamary SS, Shardell MD, Abdel-Hamid M, Ismail S, El-Ateek M, Metwally M, Mikhail N, Hashem M, Mousa A, Aboul-Fotouh A, El-Kassas M, Esmat G, Strickland GT (2009) A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine 16:391–400. doi:10.1016/j.phymed.2009.02.002

    Article  PubMed  CAS  Google Scholar 

  • El-Shitany NA, El-Haggar S, El-desoky K (2008) Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats. Food Chem Toxicol 46:2422–2428. doi:10.1016/j.fct.2008.03.033

    Article  PubMed  CAS  Google Scholar 

  • Fallah Huseini H, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Mohsin R (2006) The efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the treatment of type II diabetes: A randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 20(12):1036–1039. doi:10.1002/ptr.1988

    Article  PubMed  Google Scholar 

  • Flora K, Hahn M, Rosen H, Benner K (1998) Milk thistle (Silybum matinum) for the therapy of liver disease. Am J Gastroenterol 93(2):139–143 PII: S0002-9270(97)00082-8

    Article  PubMed  CAS  Google Scholar 

  • Gilbert SC, Emmett M, Menter A, Silverman A, Klintmalm G (1989) Cyclosporine therapy for psoriasis: serum creatinine measurements are an unreliable predictor of decreased renal function. J Am Acad Dermatol 21:470–474 PII: S0190-9622(89)70209-7

    Article  PubMed  CAS  Google Scholar 

  • Han MH, Yoon WK, Lee H, Han SB, Lee K, Park SK, Yang KH, Kim HM, Kang JS (2007) Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice. Int Immunopharmacol 7:1651–1658. doi:10.1016/j.intimp.2007.08.019

    Article  PubMed  CAS  Google Scholar 

  • Harikrishnan R, Balasundaram C, Heo MS (2010a) Herbal supplementation diets on hematology and innate immunity in goldfish against Aeromonas hydrophila. Fish Shellfish Immunol 28:354–361. doi:10.1016/j.fsi.2009.11.013

    Article  PubMed  CAS  Google Scholar 

  • Harikrishnan R, Heo J, Balasundaram C, Kim MC, Kim JS, Han YJ, Heo MS (2010b) Effect of Punica granatum solvent extracts on immune system and disease resistance in Paralichthys olivaceus against lymphocystis disease virus (LDV). Fish Shellfish Immunol 29:668–673. doi:10.1016/j.fsi.2010.07.006

    Article  PubMed  Google Scholar 

  • Haroun EM, Mahmoud OM, Adam SE (2002) Effect of feeding Cuminum cyminum fruits, Thymus vulgaris leaves or their mixture to rats. Vet Hum Toxicol 44(2):67–69 PMID: 11933909 [PubMed—indexed for MEDLINE]

    PubMed  CAS  Google Scholar 

  • Hinshaw JM (1999) Trout production (feeds and feeding methods). SRAC publication no. 223

  • Iris F, Benzie F, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76

    Google Scholar 

  • Iwashima M, Mori J, Ting X, Matsunaga T, Hayashi K, Shinoda D, Saito H, Sankawa U, Hayashi T (2005) Antioxidant and antiviral activities of plastoquinones from the brown alga Sargassum micracanthum, and a new chromene derivative converted from the plastoquinones. Biol Pharm Bull 28:374–377

    Google Scholar 

  • Jeney G, Yin G, Ardó L, Jeney Z (2009) The use of immunostimulating herbs in fish. An overview of research. Fish Physiol Biochem 35:669–676. doi:10.1007/s10695-009-9304-z

    Article  PubMed  Google Scholar 

  • Jia JD, Bauer M, Cho JJ, Ruehl M, Milani S, Boigk G, Riecken OE, Schuppan D (2001) Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen α1(I) and TIMP-1. J Hepatol 35:392–398 PII: S0l68-8278(01)00148-9

    Article  PubMed  CAS  Google Scholar 

  • Kaur M, Agarwal R (2007) Silymarin and epithelial cancer chemoprevention: how close we are to bedside? Toxicol Appl Pharmacol 224(3):350–359. doi:10.1016/j.taap.2006.11.011

    Article  PubMed  CAS  Google Scholar 

  • Kiruthiga PV, Beema Shafreen R, Karutha Pandian S, Arun S, Govindu S, Pandima Devi K (2007) Protective effect of silymarin on erythrocyte haemolysate against benzo(a) pyrene and exogenous reactive oxygen species (H2O2) induced oxidative stress. Chemosphere 68:1511–1518. doi:10.1016/j.chemosphere.2007.03.015

    Article  PubMed  CAS  Google Scholar 

  • Kohno H, Tanaka T, Kawabata K, Hirose Y, Sugie S, Tsuda H, Mori H (2002) Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 101:461–468. doi:10.1002/ijc.10625

    Article  PubMed  CAS  Google Scholar 

  • Kumar RS, Sivakumar T, Sivakumar P, Nethaji R, Vijayabasker M, Perumal P, Gupta M, Mazumder UK (2005) Hepatoprotective and in vivo antioxidant effects of Careya arbrorea against carbon tetrachloride induced liver damage in rats. Int J Mol Med Adv Sci 1(4):418–424

    Google Scholar 

  • Nencini C, Giorgi G, Micheli L (2007) Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 14:129–135. doi:10.1016/j.phymed.2006.02.005

    Article  PubMed  CAS  Google Scholar 

  • Oliveira CPMS, Lopasso FP, Laurindo FRM, Leitão RMC, Laudanna AA (2001) Protection against liver ischemia-reperfusion injury in rats by silymarin or verapamil. Transpl Proc 33(6):3010–3014 PII:S0041-1345(01)02288-6

    Article  CAS  Google Scholar 

  • Palanisamy D, Syamala S, Kannan E, Bhojraj S (2007) Protective and therapeutic effects of the Indian medicinal plant Pterocarpus santalinus on d-Galactosamine induced liver damage. Asian J Tradit Med 2(2):51–57

    CAS  Google Scholar 

  • Pradeep K, Mohan CVR, Gobianand K, Karthikeyan S (2007) Silymarin modulates the oxidant–antioxidant imbalance during diethylnitrosamine induced oxidative stress in rats. Eur J Pharmacol 560:110–116. doi:10.1016/j.ejphar.2006.12.023

    Article  PubMed  CAS  Google Scholar 

  • Premalakshmi V, Thenmozhi CD (2011) Hepatoprotective effect of hyroethanolic extract of Hybanthus enneaspermus against paracetamol induced liver damage in rats. Int J Biotechnol Biochem 7(2):239–244

    Google Scholar 

  • Ramadan LA, Roushdy HM, Abu-Senna GM, Amin NE (2002) Radio-protective effect of silymarin against radiation induced hepatotoxicity. Pharmacol Res 45(6):447–454. doi:10.1006/phrs.2002.990

    Article  PubMed  CAS  Google Scholar 

  • Ramasamy K, Agarwal R (2008) Multitargeted therapy of cancer by silymarin. Cancer Lett 269:352–362. doi:10.1016/j.canlet.2008.03.053

    Article  PubMed  CAS  Google Scholar 

  • Rao YV, Chakrabarti R (2005) Stimulation of immunity in Indian major carp Catla catla with herbal feed ingredients. Fish Shellfish Immunol 18:327–334. doi:10.1016/j.fsi.2004.08.005

    Article  PubMed  Google Scholar 

  • Rao YV, Das BK, Jyotyrmayee P, Chakrabarti R (2006) Effect of Achyranthes aspera on the immunity and survival of Labeo rohita infected with Aeromonas hydrophila. Fish Shellfish Immunol 20:263–273. doi:10.1016/j.fsi.2005.04.006

    Article  Google Scholar 

  • Šeršeň F, Vencel T, Annus J (2006) Silymarin and its components scavenge phenylglyoxylic ketyl radicals. Fitoterapia 77:525–529. doi:10.1016/j.fitote.2006.06.005

    Article  PubMed  Google Scholar 

  • Shaarawy SM, Tohamy AA, Elgendy SM, Abd Elmageed ZY, Bahnasy A, Mohamed MS, Kandil E, Kh Matrougui (2009) Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity. Int J Biol Sci 5(6):549–557 PMID: 19742242 [PubMed—indexed for MEDLINE]

    PubMed  CAS  Google Scholar 

  • Shaker E, Mahmoud H (2010) Mnaa S (2010) Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol 48:803–806. doi:10.1016/j.fct.2009.12.011

    Article  PubMed  CAS  Google Scholar 

  • Sivaram V, Babu MM, Citarasu T, Immanuel G, Murugadass S, Marian MP (2004) Growth and immune response of juvenile greasy groupers (Epinephelus tauvina) fed with herbal antibacterial active principle supplemented diets against Vibrio harveyi infections. Aquaculture 237:9–20. doi:10.1016/j.aquaculture.2004.03.014

    Article  Google Scholar 

  • Škottová N, Večeřa R, Urbánek K, Vána P, Walterová D, Cvak L (2003) Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. Pharmacol Res 47:17–26 PII: S1043-6618(02)00252-9

    Article  PubMed  Google Scholar 

  • Sobolová L, Škottová N, Večeřa R, Urbánek K (2006) Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats. Pharmacol Res 53:104–112. doi:10.1016/j.phrs.2005.09.004

    Article  PubMed  Google Scholar 

  • Soto C, Recoba R, Barrón H, Alvarez C, Favari L (2003) Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas. Compar Biochem Physiol Part C Toxicol Pharmacol 136(3):205–212. doi:10.1016/S1532-0456(03)00214-X

    Article  Google Scholar 

  • Soto C, Mena R, Luna J, Cerbón M, Larrieta E, Vital P, Uría E, Sánchez M, Recoba R, Barrón H, Favari L, Lara A (2004) Silymarin induces recovery of pancreatic function after alloxan damage in rats. Life Sci 75:2167–2180. doi:10.1016/j.lfs.2004.04.019

    Article  PubMed  CAS  Google Scholar 

  • Soto C, Pérez J, García V, Uría E, Vadillo M, Raya L (2010) Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus. Phytomedicine 17(14):1090–1094. doi:10.1016/j.phymed.2010.04.011

    Article  PubMed  CAS  Google Scholar 

  • Stickel F, Patsenker E, Schuppan D (2005) Herbal hepatotoxicity. J Hepatol 43:901–910. doi:10.1016/j.jhep.2005.08.002

    Article  PubMed  Google Scholar 

  • Toklu HZ, Tunalı-Akbay T, Erkanlı G, Yüksel M, Ercan F, Şener G (2007) Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury burns. 33:908–916. doi:10.1016/j.burns.2006.10.407

  • Toklu HZ, Tunalı-Akbay T, Velioglu-Ogunc A, Ercan F, Gedik N, Keyer-Uysal M, Sener G (2008) Silymarin, the antioxidant component of Silybum marianum, prevents sepsis-induced acute lung and brain injury. J Surg Res 145:214–222. doi:10.1016/j.jss.2007.03.072

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela A, Monica A, Soledad V, Ricardo G (1989) Selectivity of silymarin on the increase of the glutathione content in different tissues of the rats. Planta Med 55:420–422

    Article  PubMed  CAS  Google Scholar 

  • Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC (2000) Milk thistle, an herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28:1270–1273

    PubMed  CAS  Google Scholar 

  • Wu CC, Liu CH, Chang YP, Hsieh SL (2010) Effects of hot-water extract of Toona sinensis on immune response and resistance to Aeromonas hydrophila in Oreochromis mossambicus. Fish Shellfish Immunol 29:258–263. doi:10.1016/j.fsi.2010.04.021

    Article  PubMed  Google Scholar 

  • Yadava NP, Pal A, Shanker K, Bawankule DU, Gupta AK, Darokar MP, Khanuja SPS (2008) Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4-induced hepatotoxicity in Rattus norvegicus. Phytomedicine 15:1053–1061. doi:10.1016/j.phymed.2008.08.002

    Article  Google Scholar 

  • Yin G, Ardo L, Thompson KD, Adams A, Jeney Z, Jeney G (2009) Chinese herbs (Astragalus radix and Ganoderma lucidum) enhance immune response of carp, Cyprinus carpio, and protection against Aeromonas hydrophila. Fish Shellfish Immunol 26:140–145. doi:10.1016/j.fsi.2008.08.015

    Article  PubMed  Google Scholar 

  • Zuber R, Modrianský M, Dvořák Z, Rohovský P, Ulrichová J, Šimánek V, Anzenbacher P (2002) Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 16(7):632–638. doi:10.1002/ptr.1000

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the support offered from the Natural Resource Faculty; (Tehran University). The authors are also grateful to Mr. Reza Ashori and Mrs. Maryam Mossavei, laboratory technicians, for their cooperation and assistance throughout the research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahdi Banaee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banaee, M., Sureda, A., Mirvaghefi, A.R. et al. Effects of long-term silymarin oral supplementation on the blood biochemical profile of rainbow trout (Oncorhynchus mykiss). Fish Physiol Biochem 37, 885–896 (2011). https://doi.org/10.1007/s10695-011-9486-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10695-011-9486-z

Keywords

Navigation