Effect of Prenatal Silymarin Administration in the Gestational Period on Fetal Growth

Author

Department of Midwifery, School of Nursing and Midwifery, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Abstract

Background: Silymarin is a potent inhibitor of apoptosis. The present study aimed to investigate the effect of prenatal silymarin administration during the gestational period on fetal growth.
Methods: This experimental study was conducted on 24 virgin female BALB/c mice weighing 20-30 grams. One male animal was caged with two females overnight, and they were examined for the presence of a vaginal plug in the next morning. Presence of vaginal plugs was considered to be gestational day zero (GD0). The mice were randomly divided into four groups, including three groups of pregnant mice administered with silymarin via intraperitoneal injection at doses of 50, 100, and 200 mg/kg/day (groups 1, 2, and 3, respectively) during GD6-15 (organogenesis) and a control group. Animals in the control group received normal saline via the same route in equivalent volumes. Data analysis was performed in SPSS version 18.0, and the pathological scores were compared using Kruskal-Wallis, ANOVA, and Dunn’s multiple comparison tests. P-value of less than 0.05 was considered statistically significant.
Results: Administration of silymarin had no effect on the weight gain of the mothers. However, placental weight gain decreased in the second and third group compared to the other groups (P≤0.001). In addition, head circumference was observed to reduce in all the treatment groups compared to the control group (P≤0.001). Also, the findings showed significant differences in the resorption rate and weight gain in all the treatment groups compared to the control group (P=0.001).
Conclusion: According to the results, silymarin administration during gestation may lower weight gain and decrease placental circumference in the fetus of mice.

Keywords


1. Valenzuela A, Garrido A. Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin. Biol Res. 1993; 27(2):105-12.

2. Morazzoni P, Bombardelli E. Silybum marianum (Carduus marianus). Fitoterapia. 1995; 66(1):3-42.

 3. Lecomte J. Pharmacologic properties of silybin and silymarin. Rev Med Liege. 1975; 30(4):110-4.

 4. Valenzuela A, Lagos C, Schmidt K, Videla LA. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem Pharmacol. 1985; 34(12):2209-12 .

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

6. Luper S. A review of plants used in the treatment of liver disease: part 1. Alternat Med Rev. 1998; 3(6):410-21.

7. Magliulo E, Carosi PG, Minoli L, Gorini S. Studies on the regenerative capacity of the liver in rats subjected to partial hepatectomy and treated with silymarin. Arzneimittelforschung. 1973; 23:161-7.

8. Tafazoli M, Saeedi R, Gholami Robatsangi M, Mazloom R. Aloevera gel Vs. lanolin ointment in the treatment of nipple sore: a randomized clinical trial. Tehran Univ Med J. 2010; 67(10):699-704.

9. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology. 1996; 23(4):749-54.

 10. Dehmlow C, Murawski N, de Groot H. Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Life Sci. 1996; 58(18):1591-600.

 11. Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R. Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes. Carcinogenesis. 2004; 25(1):99-106.

 12. Mallikarjuna G, Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Cancer Res. 2004; 64(17):6349-56.

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

14. Ahmadi-Ashtiani HR, Rezazadeh S, Safipourian K, Afraz K, Khaki A, Rastegar H. Study the effects of oral administration of silymarin in preventing consequences of ethanol on liver during pregnancy. J Med Plants. 2010; 3(35):143-50.

15. Metcalfe AD, Hunter HR, Bloor DJ, Lieberman BA, Picton HM, Leese HJ, et al. Expression of 11 members of the BCL‐2 family of apoptosis regulatory molecules during human preimplantation embryo development and fragmentation. Mol Reprod Dev. 2004; 68(1):35-50.

16. Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NFκB, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999; 163(12):6800-9.

 17. Torchinsky A, Fein A, Toder V. Teratogen‐induced apoptotic cell death: does the apoptotic machinery act as a protector of embryos exposed to teratogens? Birth Defects Res Part C Embryo Today. 2005; 75(4):353-61.

18. Saeidi R, Tafazoli M, Gholami Robatsangi M. Kangaroo mother care for infantile colic: a randomized clinical trial. Tehran Univ Med J. 2010; 67(12):870-5.

19. Saeidi R, Ziadi Lotf Abadi M, Saeidi A, Gholami Robatsangi M. The effectiveness of mother infant interaction on infantile colic. Iran J Neonatol. 2014; 4(4):34-8.

20. Abasi E, Tafazzoli M, Esmaily H, Hasanabadi H. The effect of maternal–fetal attachment education on maternal mental health. Turkish J Med Sci. 2013; 43(5):815-20.

21. Moalem SA, Tafazolim M, Niapour M. Evaluation of teratogenic effects of zingiber officinale in mice. Iran J Basic Med Sci. 2003; 6(1):43-52 (Persian.)

22. Yuan HD, Jin GZ, Piao GC. Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice. J Ethnopharmacol. 2010; 127(2):528-33. 23. Agarwal C, Tyagi A, Kaur M, Agarwal R. Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis. 2007; 28(7):1463-70.

 24. Tyagi A, Singh RP, Agarwal C, Agarwal R. Silibinin activates p53-caspase 2 pathway and causes caspasemediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells: evidence for a regulatory loop between p53 and caspase 2. Carcinogenesis. 2006; 27(11):2269-80.

25. Son YG, Kim EH, Kim JY, Kim SU, Kwon TK, Yoon AR, et al. Silibinin sensitizes human glioma cells to TRAIL-mediated apoptosis via DR5 up-regulation and down-regulation of c-FLIP and survivin. Cancer Res. 2007; 67(17):8274-84.

26. Duan WJ, Li QS, Xia MY, Tashiro S, Onodera S, Ikejima T. Silibinin activated p53 and induced autophagic death in human fibrosarcoma HT1080 cells via reactive oxygen species-p38 and c-Jun Nterminal kinase pathways. Biol Pharm Bull. 2011; 34(1):47-53.

 27. Singh RP, Agarwal R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur J Cancer. 2005; 41(13):1969-79.

28. Endo H, Okamoto A, Yamada K, Nikaido T, Tanaka T. Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms. Int J Mol Med. 2005; 16(1):79-84.

29. Smith SC, Baker PN, Symonds EM. Increased placental apoptosis in intrauterine growth restriction. Am J Obstet Gynecol. 1997; 177(6):1395-401.

 30. Wilkinson JM. Effect of ginger tea on the fetal development of Sprague-Dawley rats. Reprod Toxicol. 2000; 14(6):507-12 .

 31. Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr. 1998; 132(3):550-2.