Document Type : Original Article
Authors
Abstract
Background and Aim: Both cell proliferation and apoptosis are required for proper development of the neonatal parenchyma of the liver. This study was conducted to evaluate the effects of swimming endurance training and silymarin supplementation during pregnancy on maternal cadmium – induced apoptosis in hepatocytes of neonates. Materials and Methods: 72 pregnant Wistar rats (200 ± 20 g) were divided into 9 groups. Cadmium chloride was given orally (400 mg/kg in drinking water) from the first day of pregnancy. Training protocol was included 60 minutes swimming for 5 days per week during pregnancy. Silymarin (100 mg/kg) was injected subcutaneously three times a week. Liver tissue was removed two days after born and apoptotic index also determined by nonradioactive in situ end labeling method using TUNEL immunocytochemical technique. The ANOVA and post hoc LSD tests were used to analyze the collected data at p≤ 0.05. Results: Apoptotic index of hepatocytes were decreased significantly in cadmium- silymarin and cadmium- silymarin-training groups (p<0.001). Swimming training caused no significant changes in apoptotic index of hepatocytes (p=0.83). Conclusion: Swimming endurance training during pregnancy probably have no effect on maternal cadmium – induced of apoptosis in hepatocytes of neonates, however, silymarin could reduce it.
Keywords
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9. Hakkak-Dokht, E., Salami, F., Rajabi, H., Hedayati, M., 2011. Effect of aerobic training and vitamins E and C supplementation on GSH and antioxidative enzymes (GPX and SOD) in pregnant rats. Journal of Olympic, vol. 3, no. 55, pp. 47-56. [persian]
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28. Scott, M., Arnold, R.L.Z., Tracey, V., Marc-Andre, R., 2006. Public health evaluation of cadmium concentrations in liver and kidney of moose (Alces alces) from four areas of Alask. Science of the Total Environment, vol. 357 pp. 103– 111.
29. Shu-Hui S., Chauying J.J., Hsiun-ing Ch., 2011. NO signaling in exercise training-induced anti-apoptotic effects in human neutrophils. Biochemical and Biophysical Research Communications, vol. 405, pp. 58–63.
30. Sonnenbichler, J., Zetl, I., 1986. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. Plant Flavonoids in Biology and Medicine, 1985. vol. 213, pp. 319-331.
31. Tsai, C.C., Wu, J.P., Lin, Y.M., Yeh, Y.L., et al. 2013. The effect of Elephantopus scaber L. on liver regeneration after partial hepatectomy. Evidence-Based Complementary and Alternative Medicine, Vol. 2013, pp. 1-11.
32. Van Pelt, L.F., 1977. Ketamine and xylazine for surgical anesthesia in rats. journal of the American Veterinary Medical Association, vol. 171, no. 9, p. 842.
33. Waalkes, M.P., 2003. Cadmium carcinogenesis. Mutation Research, vol. 533, no. 1-2, pp.107-120.
34. Waisberg, M., Joseph, P., Hale, B., Beyersmann, D., 2003. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology, vol. 192, no. 2-3, pp. 95-117.
stem cell proliferation in the presence of silymarin. Journal of Medicinal Plants, vol. 9, no. 34, pp. 156-164. [persian]
2. Boodaqi, H., Mahvi. A.H., Mohammadi, M.A., Dehqani, M.H., et al., 2009. Evaluation of amount of arsenic, cadmium and lead in soil and groundwater and its relationship with the fertilizers in Qaemshahr. Journal of Mazandaran University Medical Science, vol. 21, no. 1, pp. 20-28. [persian]
3. Bruscalupi, G., Massimi, M., Devirgiliis, L.C., Leoni, S., 2009. Multiple parameters are involved in the effects of cadmium on prenatal hepatocytes. Toxicology In Vitro, vol. 23, no. 7, pp. 1311-1318.
4. Douglas, M.T., Ying, L., 2010. Multiple roles of cadmium in cell death and survival. Chemico-Biological Interactions, vol. 188, pp. 267-275.
5. El, H.J., Sfar S., Hammouda, F., 2011. Interrelationships between cadmium, zinc and antioxidants in the liver of the rat exposed orally to relatively high doses of cadmium and zinc. Ecotoxicology and Environmental Safety, vol. 74, pp. 2099-2104.
6. Falah Hosseini, H., Hemmati, A., Alavian, S., 2004. A review of herbal medicine: Silybum marianum. Journal of Medicinal Plants, vol. 3, no. 11, pp. 14-24. [persian]
7. Faulstich, H., Jahn, W., Wieland, T., 1980. Silybin inhibition of amatoxin uptake in Ne perfused rat liver. Drug Research, vol. 30, no. 1, pp. 452-454.
8. Fraschini, F., Demartini, G., Esposti, D., 2002. Pharmacology of silymarin. Clinical Drug Investigation, vol. 22, no. 1, pp. 51-65.
9. Hakkak-Dokht, E., Salami, F., Rajabi, H., Hedayati, M., 2011. Effect of aerobic training and vitamins E and C supplementation on GSH and antioxidative enzymes (GPX and SOD) in pregnant rats. Journal of Olympic, vol. 3, no. 55, pp. 47-56. [persian]
10. Hoffman-Goetz, L., Pervaiz, N., Guan, J., 2009. Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. Brain, Behavior, and Immunity, vol. 23, no. 4, pp. 498-506.
11. Kantola, M., Purkunen, R., Kroger, P., Tooming, A., et al., 2000. Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg. Environmental Research Section, vol. 83, no. 1, pp.54-66.
12. Kim, S.H., Kim, H.B., Jang, M.H., Lim, B.V., et al., 2002. Treadmill exercise increases cell proliferation without altering of apoptosis in dentate gyrus of Sprague-Dawley rats. Life Science, vol. 71, no. 11, pp.1331-1340.
13. Koch, H.P., Loffler, E., 1985. Silymarin: Patent inhibitor of cyclic AMP phosphodiesterase. Methods and Findings in Experimental and Clinical Pharmacology, vol. 7, pp. 409-413.
14. Koumentaki, A., Anthony, F., Poston, L., Wheeler, T., 2002. Low-protein diet impairs vascular relaxation in virgin and pregnant rats. Clinical Science, vol. 102, no. 5, pp.553-560.
15. Kuriwaki, J., Nishijo, M., Honda, R., Tawara, K., et al., 2005. Effects of cadmium exposure during pregnancy on trace elements in fetal rat liver and kidney. Toxicology Letters, vol. 156, no. 3, pp. 369-376.
16. La Grange, L., Wang, M., Watkins, R., Ortiz, D., et al., 1999. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver. Journal of Ethnopharmacology, vol. 65, no. 1, pp. 53-61.
17. Lemarie. A., Lagadic-Gossmann, D., Morzadec, C., Allain, N., et al., 2004. cadmium induces caspase-independent apoptosis in liver hep3b cells: role for calcium in signaling oxidative stress-related impairment of mitochondria and relocation of endonuclease g and apoptosis-inducing factor. Free Radical Biology and Medicine, vol. 36, pp. 1517-1531.
18. Lupo, S., Hewitt, W.R., Rush, G.F., 1986. Cadmium toxicity in the isolated perfused rat liver. Toxicology Letters. vol. 34, no. 1, pp. 5-11.
19. Melen-Mucha, G., Balcerczak, E., Mucha, S., Panczyk, M., et al., 2004. Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation. Neoplasma, vol. 51, no. 4, pp. 319-324.
20. Milnerowicz, H., Nowak, P., Wielogorska, D., Wochynski, Z., et al., 2004. Effects of moderate physical exercise on blood and urine concentrations of cadium and metallothionein in runners. Biology of Sport, vol. 21, no. 1, pp. 81-92.
21. Mirdar S., Arab, A., Hedayati, M., Hajizadeh, A., 2013. Evaluation of the effect of a swimming training program on levels of lung hypoxia inducible factor-1 α (HIF-1 α) in pups of mother rats exposed to cadmium. Qom University Medical Science Journal, vol. 7, no. 3, pp. 11-20. [persian]
22. Munter, K., Faulstich, H., 1986. Characterization of a transporting system in rat hepatocytes: studies with competitive and non-competitive inhibitors of phalloidin transport. Biochimie Et Biophysica Acta (bba) - Biomembranes, vol. 860 no. 1, pp. 91-98.
23. Patel, N., Joseph, C., Corcoran, G.B., Ray, S.D., 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, vol. 245, no. 2, pp. 143-152.
24. Prater, M.R., Laudermilch, C.L., Liang, C., Holladay, S.D., 2008. Placental oxidative stress alters expression of murine osteogenic genes and impairs fetal skeletal formation. Placenta, vol. 29, pp.802–808.
25. Queira J,. 2009. Basic histology: text and atlas. Translated by: Montazeri, H. 12th ed. Tehran: Arjmand Pablication. pp. 366-378. [persian]
26. Radko, L., Cybulski, W., 2007. Application of silymarin in human and animal medicine. Journal of Pre-Clinical And Clinical Research, vol. 1, no. 1, pp. 22-26.
27. Ramasamy, K., Agarwal, R., 2008. Multitargeted therapy of cancer by silymarin. Cancer Letters, vol. 269, no. 2, pp.352-362.
28. Scott, M., Arnold, R.L.Z., Tracey, V., Marc-Andre, R., 2006. Public health evaluation of cadmium concentrations in liver and kidney of moose (Alces alces) from four areas of Alask. Science of the Total Environment, vol. 357 pp. 103– 111.
29. Shu-Hui S., Chauying J.J., Hsiun-ing Ch., 2011. NO signaling in exercise training-induced anti-apoptotic effects in human neutrophils. Biochemical and Biophysical Research Communications, vol. 405, pp. 58–63.
30. Sonnenbichler, J., Zetl, I., 1986. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. Plant Flavonoids in Biology and Medicine, 1985. vol. 213, pp. 319-331.
31. Tsai, C.C., Wu, J.P., Lin, Y.M., Yeh, Y.L., et al. 2013. The effect of Elephantopus scaber L. on liver regeneration after partial hepatectomy. Evidence-Based Complementary and Alternative Medicine, Vol. 2013, pp. 1-11.
32. Van Pelt, L.F., 1977. Ketamine and xylazine for surgical anesthesia in rats. journal of the American Veterinary Medical Association, vol. 171, no. 9, p. 842.
33. Waalkes, M.P., 2003. Cadmium carcinogenesis. Mutation Research, vol. 533, no. 1-2, pp.107-120.
34. Waisberg, M., Joseph, P., Hale, B., Beyersmann, D., 2003. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology, vol. 192, no. 2-3, pp. 95-117.
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