Original Article

Using Biochemical Findings to Study the Effect of Silymarin on the Liver of Pregnant Rat that Consumed Ethanol

Abstract

In pregnancy period, there is high risk of hepatic diseases and alcohol consumption increases such risk. Some pregnant mothers are not able to quit the habit of drinking alcohol or they are unaware of its dangers. Finding a drug which is effective and efficient in reducing ethanol misuse consequences during pregnancy can assist the decrease of harmful effects of this habit. The purpose of the current research is to investigate the effects of oral administration of silymarin in preventing consequences of ethanol consumption on the liver during pregnancy, using the rat animal model as well as biochemical findings and clinical symptoms. 45 female rats were randomly divided into 3 groups, each composed of 15 rats. After the first day of pregnancy, the study was performed as follows. The first group received distilled water. The second group was given ethanol equivalent to 35% of their total required calorie. Furthermore, the third group received the same amount of ethanol plus 200 mg/kg silymarin. In order to evaluate liver's activity, biochemical analysis was performed at days 1, 7, 14, and 21, to measure the amount of the enzymes ALT, AST, ALP, and bilirubin. The nutrition and clinical status of animal in the groups was studied and recorded 2 times daily. This study showed that silymarin's protective effects are expressed from the first day of treatment.

Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 2001;61(14):2035-63.

Trauner M, Boyer JL. Cholestatic syndromes. Curr Opin Gastroenterol 2002;18(3):314-29.

Perez MJ, Castaño B, Gonzalez-Buitrago JM, Marin JJ. Multiple protective effects of melatonin against maternal cholestasis-induced oxidative stress and apoptosis in the rat fetal liver-placenta-maternal liver trio. J Pineal Res 2007;43(2):130-9.

Reyes H. The spectrum of liver and gastrointestinal disease seen in cholestasis of pregnancy. Gastroenterol Clin North Am 1992;21(4):905-21.

Mantle D, Preedy VR. Free radicals as mediators of alcohol toxicity. Adverse Drug React Toxicol Rev 1999;18(4):235-52.

van Pelt JF, Verslype C, Crabbé T, Zaman Z, Fevery J. Primary human hepatocytes are protected against prolonged and repeated exposure to ethanol by silibinin-dihemisuccinate. Alcohol Alcohol 2003;38(5): 411-4.

Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clin Drug Invest 2002; 22(1):51-65.

Hernández R, Nazar E. Effect of silymarin in intrahepatic cholestasis of pregnancy (preliminary communication). Rev Chil Obstet Ginecol 1982;47(1):22-9.

La Grange L, Wang M, Watkins R, Ortiz D, Sanchez ME, Konst J, Lee C, Reyes E. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver. J Ethnopharmacol 1999;65(1):53-61.

Saravanan R, Viswanathan P, Pugalendi KV. Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats. Life Sci 2006;78(7):713-8.

Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C. The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury. J Ethnopharmacol 2006;107(3):361-4.

Lu ZM, Tao WY, Zou XL, Fu HZ, Ao ZH. Protective effects of mycelia of Antrodia camphorata and Armillariella tabescens in submerged culture against ethanol-induced hepatic toxicity in rats. J Ethnopharmacol 2007;110(1):160-4.

Mitchell JA, Van Kainen BR. Effects of alcohol on intrauterine oxygen tension in the rat. Alcohol Clin Exp Res 1992;16(2):308-10.

Ledig M, Holownia A, Copin JC, Tholey G, Anokhina I. Development of glial cells cultured from prenatally alcohol treated rat brain: effect of supplementation of the maternal alcohol diet with a grape extract. Neurochem Res 1996;21(3):313-7.

Ertem K, Kekilli E, Elmali N, Ceylan F. The effects of alcohol exposure during intrauterine and postnatal period on bone mineral density and bone growth and body weight in rat’s virgin offspring. Eur J General Med;3(2):54-7.

Vengeliene V, Siegmund S, Singer MV, Sinclair JD, Li TK, Spanagel R. A comparative study on alcoholpreferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake. Alcohol Clin Exp Res 2003;27(7):1048-54.

Song Z, Deaciuc I, Song M, Lee DY, Liu Y, Ji X, McClain C. Silymarin protects against acute ethanol-induced hepatotoxicity in mice. Alcohol Clin Exp Res 2006;30(3):407-13.

Kelly KJ, Meehan SM, Colvin RB, Williams WW, Bonventre JV. Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody. Kidney Int 1999;56(3):922-31.

Murillo-Fuentes L, Artillo R, Carreras O, Murillo L. Effects of maternal chronic alcohol administration in the rat: lactation performance and pup's growth. Eur J Nutr 2001;40(4):147-54.

National Institute of Health (NIH). Guide for the Care and Use of Laboratory Animals. DHEN Publication (NIH). Office of Science and Health Reports, DRR/NIH, Bethesda, MD, 1985, publication no. 85-23.

Matthews GV, Nelson MR. The management of chronic hepatitis B infection. Int J STD AIDS 2001;12(6):353-7.

Diehl AM. Liver disease in alcohol abusers: clinical perspective. Alcohol 2002;27(1):7-11.

Conti M, Malandrino S, Magistretti MJ. Protective activity of silipide on liver damage in rodents. Jpn J Pharmacol 1992;60(4):315-21.

Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982;17(4):517-21.

Das SK, Vasudevan DM. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanolinduced oxidative stress in liver. Indian J Biochem Biophys 2006;43(5):306-11.

Burd L, Martsolf JT, Juelson T. Fetal alcohol spectrum disorder in the corrections system: potenitial screening strategies. J FAS Int 2004;2:e1.

Giannola C, Buogo F, Forestiere G, Scaffidi L, Ferrigno V, Scaffidi A. A two-center study on the effects of silymarin in pregnant women and adult patients with so-called minor hepatic insufficiency. Clin Ter 1985;114(2):129-35.

Lieber CS. Biochemical factors in alcoholic liver disease. Semin Liver Dis 1993;13(2):136-53.

Apte MV, Phillips PA, Fahmy RG, Darby SJ, Rodgers SC, McCaughan GW, Korsten MA, Pirola RC, Naidoo D, Wilson JS. Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells. Gastroenterology 2000;118(4):780-94.

Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 2003;124(3):778-90.

Masini A, Ceccarelli D, Gallesi D, Giovannini F, Trenti T. Lipid hydroperoxide induced mitochondrial dysfunction following acute ethanol intoxication in rats. The critical role for mitochondrial reduced glutathione. Biochem Pharmacol 1994;47(2):217-24.

Song Z, Zhou Z, Chen T, Hill D, Kang J, Barve S, McClain C. S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice small star, filled. J Nutr Biochem 2003;14(10):591-7.

van Pelt JF, Verslype C, Crabbé T, Zaman Z, Fevery J. Primary human hepatocytes are protected against prolonged and repeated exposure to ethanol by silibinindihemisuccinate. Alcohol Alcohol 2003;38(5):411-4.

Song Z, Deaciuc I, Song M, Lee DY, Liu Y, Ji X, McClain C. Silymarin protects against acute ethanol-induced hepatotoxicity in mice. Alcohol Clin Exp Res 2006;30(3):407-13.

Müzes G, Deák G, Láng I, Nékám K, Niederland V, Fehér J. Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol). Orv Hetil1990;131(16):863-6.

Braunwald E, Fauci AD, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005.

Andreoli TE, Carpenter CCJ, Griggs RC, Loscalzo J, editors. Andreoli and Carpenter's Cecil Essentials of Medicine. 7th ed. Philadelphia: WB Saunders; 2007.

Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatology 1997;26(1):143-6.

Stewart SF, Leathart JB, Chen Y, Daly AK, Rolla R, Vay D, Mottaran E, Vidali M, Albano E, Day CP. Valinealanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis. Hepatology 2002;36(6):1355-60.

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;37(4):336-9.

Kliegman RM, Jenson HB, Marcdante KJ, Behrman RE, editors. Nelson Essentials of Pediatrics. 5th ed. Philadelphia: Elsevier Saunders; 2006.

Files
IssueVol 49, No 7 (2011) QRcode
SectionOriginal Article(s)
Keywords
Silymarin Biochemical findings Pregnancy Ethanol Liver Rat

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ahmadi-Ashtiani H, Rastegar H, Javadi L. Using Biochemical Findings to Study the Effect of Silymarin on the Liver of Pregnant Rat that Consumed Ethanol. Acta Med Iran. 1;49(7):407-413.