782
Views
45
CrossRef citations to date
0
Altmetric
Review Article

Milk thistle (Silybum Marianum) as an antidote or a protective agent against natural or chemical toxicities: a review

, , & ORCID Icon
Pages 240-254 | Received 04 Feb 2018, Accepted 31 May 2018, Published online: 22 Jul 2018

References

  • Abenavoli, L., 2010. Milk thistle in liver diseases: past, present, future. Phytotherapy Research, 24 (10), 1423–1432.
  • Adewale, O., 2015. The potential for plant derivatives against acrylamide neurotoxicity. Phytotherapy Research, 29 (7), 978–985.
  • Ahmad, I., et al., 2013. Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb-and paraquat-induced hepatotoxicity in rats. Chemico-Biological Interactions, 201 (1), 9–18.
  • Al-Anati, L., et al., 2009. Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells. Molecular Nutrition & Food Research, 53 (4), 460–466.
  • Alamolhodaei, N.S., Shirani, K., and Karimi, G., 2015. Arsenic cardiotoxicity: an overview. Environmental Toxicology and Pharmacology, 40 (3), 1005–1014.
  • Alcaraz-Contreras, Y., et al., 2016. Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats. Human & Experimental Toxicology, 35 (4), 398–403.
  • Alvarez-Erviti, L., et al., 2005. Alterations induced in vitro by ochratoxin A in rat lymphoid cells. Human &Amp; Experimental Toxicology, 24 (9), 459–466.
  • Anon, 1987. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Supplement, 7, 1–440.
  • Arshad, S., et al., 1992. Clinico-pathological studies of experimentally induced mycotoxicosis in broiler chickens. Pakistan Veterinary Journal, 12, 183–183.
  • Asghar, Z., and Masood, Z., 2008. Evaluation of antioxidant properties of silymarin and its potential to inhibit peroxyl radicals in vitro. Pakistan Journal of Pharmaceutical Sciences, 21 (3), 249–254.
  • Aydin, G., et al., 2003. Histopathologic changes in liver and renal tissues induced by Ochratoxin A and melatonin in rats. Human Experimental Toxicology, 22 (7), 383–391.
  • Baluchnejadmojarad, T., Roghani, M., and Mafakheri, M., 2010. Neuroprotective effect of silymarin in 6-hydroxydopamine hemi-parkinsonian rat: involvement of estrogen receptors and oxidative stress. Neuroscience Letters, 480 (3), 206–210.
  • Banaee, M., et al., 2015. Protective effects of silymarin extract on malthion-induced zebra cichlid (Cichlasoma nigrofasciatum) hepatotoxicity. Iranian Journal of Toxicology, 9 (28), 1239–1246.
  • Begg, E.J., and Barclay, M.L., 1995. Aminoglycosides-50 years on. British Journal of Clinical Pharmacology, 39 (6), 597–603.
  • Bektur, N.E., et al., 2016. Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice. Toxicology and Industrial Health, 32 (4), 589–600.
  • Blonde-Cynober, F., et al., 1994. Assessment of the carbon tetrachloride-induced cirrhosis model for studies of nitrogen metabolism in chronic liver disease. Annals of Nutrition and Metabolism, 38 (4), 238–248.
  • Blum, R.H., and Carter, S.K., 1974. Adriamycin: a new anticancer drug with significant clinical activity. Annals of Internal Medicine, 80 (2), 249–259.
  • Bondarenko, S., et al., 2004. Persistence of selected organophosphate and carbamate insecticides in waters from a coastal watershed. Environmental Toxicology and Chemistry, 23 (11), 2649–2654.
  • Bongiovanni, G.A., Soria, E.A., and Eynard, A.R., 2007. Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells. Food and Chemical Toxicology, 45 (6), 971–976.
  • Borsari, M., et al., 2001. Silybin, a new iron-chelating agent. Journal of Inorganic Biochemistry, 85 (2-3), 123–129.
  • Campos, R., et al., 1989. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Medica, 55 (5), 417–419.
  • Cebral, E., et al., 1997. Impaired mouse fertilization by low chronic alcohol treatment. Alcohol and Alcoholism (Oxford, Oxfordshire), 32 (5), 563–572.
  • Cecen, E., et al., 2011. Protective effects of silymarin against doxorubicin-induced toxicity. Asian Pacific Journal of Cancer, 12 (10), 2697–2704.
  • Cersosimo, M.G., and Koller, W.C., 2006. The diagnosis of manganese-induced parkinsonism. Neurotoxicology, 27 (3), 340–346.
  • Chand, N., et al., 2011. Protective effects of milk thistle (Silybum marianum) against aflatoxin B1 in broiler chicks. Asian-Australasian Journal of Animal Sciences, 24 (7), 1011–1018.
  • Chen, J.H., et al., 2004. Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants. The American Journal of Clinical Nutrition, 80 (3), 742–751.
  • Chlopčíková, Š., et al., 2004. Chemoprotective effect of plant phenolics against anthracycline‐induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Phytotherapy Research, 18 (2), 107–110.
  • Cho, S.I., Lee, J.E., and Do, N.Y., 2014. Protective effect of silymarin against cisplatin-induced ototoxicity. International Journal of Pediatric Otorhinolaryngology, 78 (3), 474–478.
  • Chouhan, S., et al., 2011. Silymarin and quercetin abrogates fluoride induced oxidative stress and toxic effects in rats. Molecular & Cellular Toxicology, 7 (1), 25–32.
  • Chrungoo, V. J., Singh, K., and Singh, J., 1997. Silymarin mediated differential modulation of toxicity induced by carbon tetrachloride, paracetamol and D-galactosamine in freshly isolated rat hepatocytes. Indian Journal of Experimental Biology, 35 (6), 611–617.
  • Chtourou, Y., et al., 2014. Protective role of silymarin against manganese-induced nephrotoxicity and oxidative stress in rat. Environmental Toxicology, 29 (10), 1147–1154.
  • Cicek, E., et al., 2005. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Human Experimental Toxicology, 24 (2), 79–87.
  • de Figueiredo, D.R., et al., 2004. Microcystin-producing blooms–a serious global public health issue. Ecotoxicology and Environmental Safety , 59 (2), 151–163.
  • De La Puerta, R., et al., 1996. Effect of silymarin on different acute inflammation models and on leukocyte migration. The Journal of Pharmacy and Pharmacology, 48 (9), 968–970.
  • de Punder, K., and Pruimboom, L., 2015. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Frontiers in Immunology, 6, 223.
  • Dorri, M., Hashemitabar, S., and Hosseinzadeh, H., 2018. Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug and Chemical Toxicology, 1, 14.
  • Dorri, S. A., et al., 2015. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iranian Journal of Basic Medical Sciences, 18 (10), 958–966.
  • Draz, E. I., et al., 2015. Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs. Pharmacological Reports, 67 (2), 317–325.
  • Dutta, M., et al., 2014. Silymarin protects against copper-ascorbate induced injury to goat cardiac mitochondria in vitro: involvement of antioxidant mechanism (s). International Journal of Pharmacy and Pharmaceutical Sciences, 6, 422–429.
  • El-Awady el, S.E., et al., 2011. Cisplatin-induced cardiotoxicity: mechanisms and cardioprotective strategies. European Journal of Pharmacology, 650 (1), 335–341.
  • El-Shitany, N.A., El-Haggar, S., and El-desoky, K., 2008. Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats. Food and Chemical Toxicology , 46 (7), 2422–2428.
  • Escalante, T., et al., 2011. Key events in microvascular damage induced by snake venom hemorrhagic metalloproteinases. Journal of Proteomics, 74 (9), 1781–1794.
  • Eskandari, F., and Momeni, H.R., 2016. Protective effect of silymarin on viability, motility and mitochondrial membrane potential of ram sperm treated with sodium arsenite. International Journal of Reproductive Biomedicine, 14 (6), 397–402.
  • Eskandari, F., and Momeni, H.R., 2016. Silymarin protects plasma membrane and acrosome integrity in sperm treated with sodium arsenite. International Journal of Reproductive Biomedicine, 14 (1), 47–52.
  • Essid, E., Dernawi, Y., and Petzinger, E., 2012. Apoptosis induction by OTA and TNF-alpha in cultured primary rat hepatocytes and prevention by silibinin. Toxins (Basel), 4 (11), 1139–1156.
  • Essid, E., and Petzinger, E., 2011. Silibinin pretreatment protects against ochratoxin A-mediated apoptosis in primary rat hepatocytes. Mycotoxin Research, 27 (3), 167–176.
  • Falke, H.E., and Zwennis, W.C., 1990. Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. 1. Biochemical and clinical effects. Archives of Toxicology, 64 (7), 522–529.
  • Farghali, H., 2000. Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacological Research, 41 (2), 231–237.
  • Favari, L., and Perez-Alvarez, V., 1997. Comparative effects of colchicine and silymarin on CCl4-chronic liver damage in rats. Archives of Medical Research, 28 (1), 11–17.
  • Fehér, J., Lengyel, G., and Blázovics, A., 1998. Oxidative stress in the liver and biliary tract diseases. Scandinavian Journal of Gastroenterology. Supplement, 228, 38–46.
  • Fracasso, M.E., et al., 2002. Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C. Mutation Research, 515 (1-2), 159–169.
  • Friedman, M., 2003. Chemistry, biochemistry, and safety of acrylamide. A review. Journal of Agricultural and Food Chemistry, 51 (16), 4504–4526.
  • Geed, M., et al., 2014. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP + injection in rats. Pharmacology Biochemistry & Behavior, 117, 92–103.
  • Geyikoglu, F., et al., 2013. The genotoxic, hepatotoxic, nephrotoxic, haematotoxic and histopathological effects in rats after aluminium chronic intoxication. Toxicology and Industrial Health, 29 (9), 780–791.
  • Gharagozloo, M., Khoshdel, Z., and Amirghofran, Z., 2008. The effect of an iron (III) chelator, silybin, on the proliferation and cell cycle of Jurkat cells: a comparison with desferrioxamine. European Journal of Pharmacology, 589 (1-3), 1–7.
  • Guo, T.L., et al., 1998. Mercuric chloride induces apoptosis in human T lymphocytes: evidence of mitochondrial dysfunction. Toxicology and Applied Pharmacology, 153 (2), 250–257.
  • Hamid, A.S., et al., 2013. Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention. Oncology Letters, 5 (4), 1087–1092.
  • Hao, S., et al., 2002. Protective effect of extra metallothioneins from rabbit liver induced by zinc on toxicity of lead in rat primary hepatocyte culture. Wei Sheng Yan Jiu, 31 (4), 229–231.
  • Hillam, R.P., and Ozkan, A.N., 1986. Comparison of local and systemic immunity after intratracheal, intraperitoneal, and intravenous immunization of mice exposed to either aerosolized or ingested lead. Environmental Research, 39 (2), 265–277.
  • Hosseini, S.M., et al., 2017. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iranian Journal of Basic Medical Sciences, 20 (8), 927–939.
  • Hu, Q., et al., 2015. Rapid methods for detecting acrylamide in thermally processed foods: a review. Food Control, 56, 135–146.
  • Jain, A., et al., 2011. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and Environmental Safety, 74 (4), 607–614.
  • Jalali, M. R., et al., 2010. Effects of silymarin and polyvalent antivenom (Pva) on renal biochemical indicators after envenomation with Hemiscorpius lepturus scorpion venom in rats. Biochemical and Cellular Archives, 10 (1), 123–128.
  • Jangra, A., et al., 2015. Hesperidin and silibinin ameliorate aluminum-induced neurotoxicity: modulation of antioxidants and inflammatory cytokines level in mice hippocampus. Biological Trace Element Research, 168 (2), 462–471.
  • Jayaraj, R., et al., 2007. Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice. Environmental Toxicology, 22 (5), 472–479.
  • Jia, J.D., et al., 2001. Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1. Journal of Hepatology, 35 (3), 392–398.
  • Kang, J.S., et al., 2004. Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol, 67 (1), 175–181.
  • Karimi, G., Ramezani, M., and Tahoonian, Z., 2005. Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evidence-Based Complementary and Alternative Medicine, 2 (3), 383–386.
  • Kemparaju, K., and Girish, K.S., 2006. Snake venom hyaluronidase: a therapeutic target. Cell Biochemistry and Function, 24 (1), 7–12.
  • Khandelwal, P.J., Herman, A.M., and Moussa, C.E.-H., 2011. Inflammation in the early stages of neurodegenerative pathology. Journal of Neuroimmunology, 238 (1-2), 1–11.
  • Khatoon, A., et al., 2013. Amelioration of ochratoxin A-induced immunotoxic effects by silymarin and Vitamin E in White Leghorn cockerels. Journal of Immunotoxicology, 10 (1), 25–31.
  • Kim, J., and Sharma, R.P., 2006. Cadmium-induced apoptosis in murine macrophages is antagonized by antioxidants and caspase inhibitors. Journal of Toxicology and Environmental Health, Part A, 69 (12), 1181–1201.
  • Kim, S.H., and Sharma, R.P., 2004. Mercury-induced apoptosis and necrosis in murine macrophages: role of calcium-induced reactive oxygen species and p38 mitogen-activated protein kinase signaling. Toxicology and Applied Pharmacology, 196 (1), 47–57.
  • Kovarik, J.M., and Burtin, P., 2003. Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases. Expert Opinion on Emerging Drugs, 8 (1), 47–62.
  • Kronbach, T., Fischer, V., and Meyer, U.A., 1988. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clinical Pharmacology and Therapeutics, 43 (6), 630–635.
  • Kumar, V., and Gill, K.D., 2014. Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its amelioration: a review. Neurotoxicology, 41, 154–166.
  • Lee, T.Y., et al., 2003. Protective mechanism of salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. Journal of Pharmacological Sciences, 91 (3), 202–210.
  • Lee, Y., et al., 2015. Silibinin suppresses astroglial activation in a mouse model of acute Parkinson's disease by modulating the ERK and JNK signaling pathways. Brain Research, 1627, 233–242.
  • Lee, Y., et al., 2015. Silibinin prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease via mitochondrial stabilization. Journal of Neuroscience Research, 93 (5), 755–765.
  • Letteron, P., et al., 1990. Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. Biochemical Pharmacology, 39 (12), 2027–2034.
  • Li, L., et al., 2017. Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells. Food and Chemical Toxicology, 102, 93–101.
  • Lu, P., et al., 2009. Silibinin attenuates amyloid β25–35 peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-α in mice. Journal of Pharmacology and Experimental Therapeutics, 331 (1), 319–326.
  • Lu, P., et al., 2009. Silibinin prevents amyloid β peptide‐induced memory impairment and oxidative stress in mice. British Journal of Pharmacology, 157 (7), 1270–1277.
  • Lucena, M.I., et al., 2002. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled. International Journal of Clinical Pharmacology and Therapeutics, 40 (1), 2–8.
  • Luper, S., 1998. A review of plants used in the treatment of liver disease: part 1. Alternative Medicine Review , 3 (6), 410–421.
  • Manna, S. K., et al., 1999. Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. Journal of Immunology, 163 (12), 6800–6809.
  • Mansour, H.H., Hafez, H.F., and Fahmy, N.M., 2006. Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. Journal of Biochemistry and Molecular Biology, 39 (6), 656–661.
  • Marchlewicz, M., et al., 1993. Effect of long-term exposure to lead on testis and epididymis in rats. Folia Histochemica Et Cytobiologica, 31 (2), 55–62.
  • Mehdizadeh, R., et al., 2013. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iranian Journal of Basic Medical Sciences, 16 (1), 56–63.
  • Mehri, S., et al., 2016. Evaluation of the neuroprotective effect of silymarin on acrylamide-induced neurotoxicity. Jundishapur Journal of Natural Pharmaceutical Products, 11 (4), e37644.
  • Meili, S., et al., 2016. Inhibitory effect of silymarin preconditioning on acrylamide-induced apoptosis in hepatocyte and its mechanism. Journal of Chinese Institute of Food Science and Technology, 4, 18–24.
  • Mereish, K.A., and Solow, R., 1990. Effect of antihepatotoxic agents against microcystin-LR toxicity in cultured rat hepatocytes. Pharmaceutical Research, 7 (3), 256–261.
  • Merxmuller, H., et al., 1977. The biology and chemistry of compositae. In V.H. Heyood, J.B. Harborne and B.L. Turner, eds. London: Academic Press, 586.
  • Mira, L., Silva, M., and Manso, C.F., 1994. Scavenging of reactive oxygen species by silibinin dihemisuccinate. Biochemical Pharmacology, 48 (4), 753–759.
  • Mohammadzadeh, L., et al., 2017a. Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats. Environmental Science and Pollution Research, 25 (5), 4904–4914.
  • Mohammadzadeh, N., Mehri, S., and Hosseinzadeh, H., 2017. Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities. Iranian Journal of Basic Medical Sciences, 20 (5), 538–551.
  • Momeni, A., et al., 2015. Effect of silymarin in the prevention of Cisplatin nephrotoxicity, a clinical trial study. Journal of Clinical and Diagnostic Research, 9 (4), OC11–Oc13.
  • Moon, K., Guallar, E., and Navas-Acien, A., 2012. Arsenic exposure and cardiovascular disease: an updated systematic review. Current Atherosclerosis Reports, 14 (6), 542–555.
  • Moulisova, V., et al., 2006. Silybin reduces lipid peroxidation of rat hepatocyte membrane caused by cyclosporin A. Biochemistry (Mosc), 71 (10), 1110–1114.
  • Murata, N., et al., 2010. Silymarin attenuated the amyloid beta plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model. Bioscience, Biotechnology, and Biochemistry, 74 (11), 2299–2306.
  • Murphy, C.J., and Oudit, G.Y., 2010. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. Journal of Cardiac Failure, 16 (11), 888–900.
  • Muthumani, M., and Prabu, S.M., 2014. Silibinin potentially attenuates arsenic-induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. Cardiovascular Toxicology, 14 (1), 83–97.
  • Muzes, G., et al., 1991. Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme. Acta Physiologica Hungarica, 78 (1), 3–9.
  • Nabavi, S., et al., 2011. Protective effects of curcumin against fluoride-induced oxidative stress in the rat brain. Neurophysiology, 43 (4), 287–291.
  • Nabavi, S.M., et al., 2012. Neuroprotective effects of silymarin on sodium fluoride-induced oxidative stress. Journal of Fluorine Chemistry, 142, 79–82.
  • Nabavi, S.M., et al., 2012. Cytoprotective effect of silymarin against sodium fluoride-induced oxidative stress in rat erythrocytes. Fluoride, 45 (1), 27–34.
  • Najafzadeh, H., et al., 2010. Comparison of the prophylactic effect of silymarin and deferoxamine on iron overload-induced hepatotoxicity in rat. Journal of Medical Toxicology, 6 (1), 22–26.
  • Nanjaraj Urs, A.N., et al., 2015. Progressive hemorrhage and myotoxicity induced by echis carinatus venom in murine model: neutralization by inhibitor cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) ethane-1,2-diamine and silymarin. PLoS One, 10 (8), e0135843.
  • Navidi-Shishaone, M., et al., 2014. Co-Administration of silymarin and deferoxamine against kidney, liver and heart iron deposition in male iron overload rat model. International Journal of Preventive Medicine, 5 (1), 110–116.
  • Nencini, C., Giorgi, G., and Micheli, L., 2007. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 14 (2-3), 129–135.
  • Ninsontia, C., et al., 2011. Silymarin selectively protects human renal cells from cisplatin-induced cell death. Pharmaceutical Biology, 49 (10), 1082–1090.
  • O'Brien, E., and Dietrich, D.R., 2005. Ochratoxin A: the continuing enigma. Critical Reviews in Toxicology, 35 (1), 33–60.
  • Olaleye, M., Adegboye, O., and Akindahunsi, A., 2006. Alchornea cordifolia extract protects wistar albino rats against acetaminophen-induced liver damage. African Journal of Biotechnology, 5 (24), 2439–2445.
  • Ottai, M., and Abdel-Moniem, A., 2006. Genetic parameter variations among milk thistle, Silybum marianum varieties and varietal sensitivity to infestation with seed-head weevil, Larinus latus Herbst. International Journal of Agriculture and Biology, 6, 862–866.
  • Par, A., et al., 2000. Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C. Orvosi Hetilap, 141 (30), 1655–1659.
  • Patel, N., et al., 2010. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver. Toxicology and Applied Pharmacology, 245 (2), 143–152.
  • Pereira, N.A., et al., 1994. Pharmacological screening of plants recommended by folk medicine as snake venom antidotes; IV. Protection against Jararaca venom by isolated constituents1. Planta Medica, 60 (02), 99–100.
  • Pérez-H, J., et al., 2014. Neuroprotective effect of silymarin in a MPTP mouse model of Parkinson's disease. Toxicology, 319, 38–43.
  • Phillipson, J.D., and Anderson, L.A., 1989. Ethnopharmacology and western medicine. Journal of Ethnopharmacology, 25 (1), 61–72.
  • Podder, B., et al., 2012. Antioxidant effect of silymarin on paraquat-induced human lung adenocarcinoma A549 cell line. Food and Chemical Toxicology , 50 (9), 3206–3214.
  • Pook, S.H., Toh, C.K., and Mahendran, R., 2006. Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity. Cancer Letters, 238 (1), 146–152.
  • Pourbakhsh, H., et al., 2014. Effect of Nigella sativa fixed oil on ethanol toxicity in rats. Iranian Journal of Basic Medical Sciences, 17 (12), 1020–1031.
  • Prabu, S.M., and Muthumani, M., 2012. Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats. Molecular Biology Reports, 39 (12), 11201–11216.
  • Rahim, M., et al., 1999. Immuno-modulatory and growth inhibitory effects of mycotoxins (Aflatoxin B1) in broiler chickens and the reversal influence of hydrated sodium calcium aluminosilicate. Pakistan Journal of Biological Sciences (Pakistan), 2 (3), 1027–1029.
  • Rameshrad, M., Razavi, B.M., and Hosseinzadeh, H., 2017. Protective effects of green tea and its main constituents against natural and chemical toxins: A comprehensive review. Food and Chemical Toxicology , 100, 115–137.
  • Rao, P.V., Jayaraj, R., and Bhaskar, A.S., 2004. Protective efficacy and the recovery profile of certain chemoprotectants against lethal poisoning by microcystin-LR in mice. Toxicon, 44 (7), 723–730.
  • Raskovic, A., et al., 2011. The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules, 16 (10), 8601–8613.
  • Rastogi, R., Srivastava, A.K., and Rastogi, A.K., 2001. Long term effect of aflatoxin B(1) on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarin. Phytotherapy Research, 15 (4), 307–310.
  • Razavi, B.M., and Hosseinzadeh, H., 2015. Saffron as an antidote or a protective agent against natural or chemical toxicities. DARU Journal of Pharmaceutical Sciences, 23 (1), 31.
  • Rechnagel, R.O., and Glende, E.A., Jr. 1973. Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Critical Reviews in Toxicology, 2 (3), 263–297.
  • Saad, S.Y., Najjar, T.A., and Alashari, M., 2004. Role of non‐selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin‐induced nephrogonadal toxicity in rats. Clinical and Experimental Pharmacology and Physiology, 31 (12), 862–867.
  • Saller, R., Meier, R., and Brignoli, R., 2001. The use of silymarin in the treatment of liver diseases. Drugs, 61 (14), 2035–2063.
  • Santamaria, A., 2008. Manganese exposure, essentiality & toxicity. The Indian Journal of Medical Research, 128 (4), 484.
  • Sauvant, C., Holzinger, H., and Gekle, M., 2005. The nephrotoxin ochratoxin A induces key parameters of chronic interstitial nephropathy in renal proximal tubular cells. Cellular Physiology and Biochemistry, 15 (1-4), 125–134.
  • Schreiber, S.L., and Crabtree, G.R., 1992. The mechanism of action of cyclosporin A and FK506. Immunology Today, 13 (4), 136–142.
  • Shafiq-ur-Rehman, S., 1991. Effects of lead on the behavioral complex stereotypes and regional brain dopamine levels in rats. Archives of Environmental Contamination and Toxicology, 20 (4), 527–530.
  • Shahbazi, F., et al., 2015. Effect of silymarin administration on cisplatin nephrotoxicity: report from a pilot, randomized, double-blinded, placebo-controlled clinical trial. Phytotherapy Research, 29 (7), 1046–1053.
  • Shalan, M.G., et al., 2005. Amelioration of lead toxicity on rat liver with vitamin C and silymarin supplements. Toxicology, 206 (1), 1–15.
  • Shin, J.H., et al., 2013. Protective effect of silymarin against ethanol-induced gastritis in rats: role of sulfhydryls, nitric oxide and gastric sensory afferents. Food and Chemical Toxicology, 55, 353–357.
  • Shukla, R., et al., 1991. Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati Lead Study. Pediatrics, 88 (5), 886–892.
  • Silbergeld, E.K., Sacci, J.B., Jr., and Azad, A.F., 2000. Mercury exposure and murine response to Plasmodium yoelii infection and immunization. Immunopharmacology and Immunotoxicology, 22 (4), 685–695.
  • Singhal, N.K., et al., 2011. Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse . Journal of Pineal Research, 50 (2), 97–109.
  • Skottova, N., et al., 2003. Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. Pharmacological Research, 47 (1), 17–26.
  • Smeyne, R.J., and Jackson-Lewis, V., 2005. The MPTP model of Parkinson's disease. Brain Research. Molecular Brain Research, 134 (1), 57–66.
  • Soares, A.M., et al., 2005. Medicinal plants with inhibitory properties against snake venoms. Current Medicinal Chemistry, 12 (22), 2625–2641.
  • Song, X., et al., 2016. Protective effect of silibinin on learning and memory impairment in LPS-treated rats via ROS-BDNF-TrkB Pathway. Neurochemical Research, 41 (7), 1662–1672.
  • Song, Z., et al., 2006. Silymarin protects against acute ethanol‐induced hepatotoxicity in mice. Alcoholism: Clinical and Experimental Research, 30 (3), 407–413.
  • Soria, E.A., Eynard, A.R., and Bongiovanni, G.A., 2010. Cytoprotective effects of silymarin on epithelial cells against arsenic-induced apoptosis in contrast with quercetin cytotoxicity. Life Science, 87 (9-10), 309–315.
  • Srinivasan, R., and Ramprasath, C., 2012a. Beneficial role of silibinin in monitoring the cadmium induced hepatotoxicity in Albino Wistar rats. Recent Research in Science and Technology, 4 (1), 46–52.
  • Srinivasan, R., and Ramprasath, C., 2012b. Protective role of silibinin in cadmium induced changes of acetylcholinesterase, ATPases and oxidative stress in brain of albino wistar rats. Journal of Ecobiotechnology, 3 (11), 34–39.
  • Srivastava, G., et al., 2012. Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. Free Radical Biology and Medicine, 52 (8), 1294–1306.
  • Sroczynski, J., et al., 1987. Biochemical studies in the evaluation of the health status of workers chronically exposed to lead. Med Pr, 38 (6), 429–436.
  • Steinberg, D., 1997. Low density lipoprotein oxidation and its pathobiological significance. The Journal of Biological Chemistry, 272 (34), 20963–20966.
  • Stoev, S.D., et al., 2000. Influence of ochratoxin A and an extract of artichoke on the vaccinal immunity and health in broiler chicks. Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Fur Toxikologische Pathologie, 52 (1), 43–55.
  • Stolf, A.M., Cardoso, C.C., and Acco, A., 2017. Effects of silymarin on diabetes mellitus complications: a review. Phytotherapy Research : Ptr, 31 (3), 366–374.
  • Suntres, Z.E., 2002. Role of antioxidants in paraquat toxicity. Toxicology, 180 (1), 65–77.
  • Tacar, O., Sriamornsak, P., and Dass, C.R., 2013. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of Pharmacy and Pharmacology, 65 (2), 157–170.
  • Tedesco, D., et al., 2004. Efficacy of silymarin-phospholipid complex in reducing the toxicity of aflatoxin B1 in broiler chicks. Poultry Science, 83 (11), 1839–1843.
  • Teixeira, C.F., et al., 2003. Inflammatory effects of snake venom myotoxic phospholipases A2. Toxicon, 42 (8), 947–962.
  • Thomas, M.J., et al., 1997. A comparison of the kinetics of low-density lipoprotein oxidation initiated by copper or by azobis (2-amidinopropane). Free Radical Biology and Medicine, 23 (6), 927–935.
  • Tomljenovic, L., 2011. Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?. Journal of Alzheimer's Disease, 23 (4), 567–598.
  • Tsai, J.H., et al., 2008. Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. Journal of Viral Hepatitis, 15 (7), 508–514.
  • Vahdati Hasani, F., et al., 2016. Silybum marianum extract reduced acrylamide-induced neurotoxicity in both in vitro and in vivo assessments. Medical Journal of Mashhad University of Medical Sciences, 59, 60.
  • Vakulenko, S.B., and Mobashery, S., 2003. Versatility of aminoglycosides and prospects for their future. Clinical Microbiology Reviews, 16 (3), 430–450.
  • Valenzuela, A., et al., 1989. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Medica, 55 (5), 420–422.
  • Valenzuela, A., Guerra, R., and Videla, L.A., 1986. Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Medica, 52 (06), 438–440.
  • Varzi, H.N., et al., 2007. Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. Journal of Veterinary Pharmacology and Therapeutics, 30 (5), 477–481.
  • Vázquez-Claverie, M., et al., 2009. Acute and chronic 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine administrations elicit similar microglial activation in the substantia nigra of monkeys. Journal of Neuropathology & Experimental Neurology, 68 (9), 977–984.
  • von Schönfeld, J., Weisbrod, B., and Müller, M.K., 1997. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cellular and Molecular Life Sciences, 53 (12), 917–920.
  • Vyskocil, A., et al., 1991. The urinary excretion of specific proteins in workers exposed to lead. Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement, 14, 218–221.
  • Wahsha, M., and Al-Jassabi, S., 2009. The role of Silymarin in the protection of mice liver damage against Microcystin-LR toxicity. Jordan Journal of Biological Sciences, 2 (2), 63–68.
  • Wang, C.-H., et al., 2007. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases. Toxicology and Applied Pharmacology, 222 (3), 315–326.
  • Wang, M.J., et al., 2002. Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. European Journal of Neuroscience, 16 (11), 2103–2112.
  • Wang, Y., et al., 2011. Iron-induced cardiac damage: role of apoptosis and deferasirox intervention. The Journal of Pharmacology and Experimental Therapeutics, 336 (1), 56–63.
  • Winneke, G., Collet, W., and Lilienthal, H., 1988. The effects of lead in laboratory animals and environmentally-exposed children. Toxicology, 49 (2-3), 291–298.
  • Xu, C., et al., 2007. Protective effects of green tea polyphenols against subacute hepatotoxicity induced by microcystin-LR in mice. Environmental Toxicology and Pharmacology, 24 (2), 140–148.
  • Yaghmaei, P., et al., 2014. Silymarin effect on amyloid-β plaque accumulation and gene expression of APP in an Alzheimer's disease rat model. Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 22 (1), 24.
  • Yamauchi, H., et al., 2004. Evaluation of DNA damage in patients with arsenic poisoning: urinary 8-hydroxydeoxyguanine. Toxicology and Applied Pharmacology, 198 (3), 291–296.
  • Yokel, R.A., and McNamara, P.J., 2001. Aluminium toxicokinetics: an updated minireview. Pharmacol. Toxicol, 88 (4), 159–167.
  • Zhou, B., et al., 2006. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. Journal of Pharmacological Sciences, 102 (4), 387–395.
  • Zicca, A., et al., 2002. Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats. European Journal of Pharmacology, 442 (3), 265–272.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.