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Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2008 Dec 20;23(4):356–360. doi: 10.1007/s12291-008-0078-3

Calcium antagonist prevents calcium flux induced necrosis and apoptosis in ischemic reperfusion of rat liver

Pronobesh Chattopadhyay 1,2,✉, Nevneet Verma 1, Anurag Verma 1, Gunjan Shukla 3, Arun Kumar Wahi 1
PMCID: PMC3453145  PMID: 23105786

Abstract

Ca2+ accumulation in mitochondria is responsible for the cell abnormality associated with ischemia and reperfusion injury. The present study was aimed to evaluate the efficacy of Ca2+ channel blocker- amlodipine on the mitochondrial Ca2+ accumulation in ischemic and reperfusion (I/R) induced liver injury. Eighteen wistar rats were divided in sham-operated control group-I (n = 6), ischemia and reperfusion group-II (n = 6) and amlodipine treated group-III (1 mg/kg body weight /daily by oral route for 7 days before induced ischemia reperfusion manouver) (n = 6). Rats were subjected to 1h of hepatic ischemia followed by 3 h reperfusion. Mitochondrial Ca2+ content was measured and damage of mitochondria was confirmed by transmission electron microscopic examination. Bcl-2 gene expression was measured by reverse transcriptase polymerase chain reaction method. Pretreatment with Amlodipine effectively counteracted the alternation in mitochondrial Ca2+ content. TEM and expression of Bcl-2 protein confirms the restoration of cellular normalcy and accredits the cytoprotective role of Amlodipine against I/R induced hepatic injury. These findings showed that the mechanism of regulation of Bcl-2 gene expression by amlodipine may be the inhibitory action of Ca2+ entry into mitochondria and prevent apoptosis and necrosis.

Key Words: Calcium channel blocker, Amlodipine, Ischemic and reperfusion injury

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References

  • 1.Toledo-Pereyra L.H., Simmons R.L., Najarian J.A. Protection of the ischemic liver by donor pretreatment before transplantation. Am J Surg. 1975;129:513–517. doi: 10.1016/0002-9610(75)90308-6. [DOI] [PubMed] [Google Scholar]
  • 2.Elimadi A., Sapena R., Settaf A., Louet H., Tillement J., Morin D. Attenuation of liver normothermic ischemia-reperfusion injury by preservation of mitochondrial functions with S-15176 a potent trimetazidine derivative. Biochem Pharmacol. 2001;62:509–516. doi: 10.1016/S0006-2952(01)00676-1. [DOI] [PubMed] [Google Scholar]
  • 3.Detmers P.A., Lo S.K., Olsen-Egbert E., Walz A., Baggiolini M., Cohn Z.A. Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J Exp Med. 1990;171:1155–1162. doi: 10.1084/jem.171.4.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Nieminen A.L., Byrne A.M., Herman B., Lemasters J.J. Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD (P) H and reactive oxygen species. Am J Physiol Cell Physiol. 1997;272:C1286–C1294. doi: 10.1152/ajpcell.1997.272.4.C1286. [DOI] [PubMed] [Google Scholar]
  • 5.Siesjo B.K., Bengtsson F. Calcium fluxes, calcium antagonists and calcium related pathology in brain ischemia, hypoglycemia and spreading depression: a unifying hypothesis. J Cerb Blood Flow Metab. 1989;9:127–140. doi: 10.1038/jcbfm.1989.20. [DOI] [PubMed] [Google Scholar]
  • 6.Qian T., Nieminen A.L., Herman B., Lemasters J.J. Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes. Am J Physiol Cell Physiol. 1997;273:C1783–C1792. doi: 10.1152/ajpcell.1997.273.6.C1783. [DOI] [PubMed] [Google Scholar]
  • 7.Cory S., Huang D.C., Adams J.M. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003;22:8590–8607. doi: 10.1038/sj.onc.1207102. [DOI] [PubMed] [Google Scholar]
  • 8.Chattopadhyay P., Sharma A.K., Wahi A.K. Folic acid protects hepatobiliary function in ischemic reperfusion of rat liver. Ind J Gastroenterology. 2007;26:95–96. [PubMed] [Google Scholar]
  • 9.Jonshon D., Lardy H. Isolation of liver kidney mitochondria. In: Estarbook R.W., editor. Methods in enzymology. Vol 10. London: Academic Press; 1947. p. P94. [Google Scholar]
  • 10.Kreamer B., Stacker J.L., Sawada N., Sattler G.L., Hsia M.T., Pitot H.C. Use of low- speed, iso-density percoll centrifugation method to increase the viability of isolated rat hepatocytes preparations. In Vitro Cell Dev Biol. 1986;22:201–211. doi: 10.1007/BF02623304. [DOI] [PubMed] [Google Scholar]
  • 11.Tong X., Lin S., Fujii N., Hou D. X. Echinocystic acid induces apoptosis in HL-60 cells through mitochondria mediated death pathway. Cancer Lett. 2004;212:21–32. doi: 10.1016/j.canlet.2004.03.035. [DOI] [PubMed] [Google Scholar]
  • 12.Satoh H., Mukai M., Urushida T., Katoh H., Terada H., Hayashi H. Importance of Ca2+ influx by Na+/Ca2+ exchange under normal and sodium-loaded conditions in mammalian ventricles. Mol Cell Biochem. 2003;242:11–17. doi: 10.1023/A:1021192318882. [DOI] [PubMed] [Google Scholar]
  • 13.Farrow S.N., White J.H., Martinou I., Raven T., Punm K.T., Grinham C.J., Martinou J.C., Brown R. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature. 1995;374:731–733. doi: 10.1038/374731a0. [DOI] [PubMed] [Google Scholar]
  • 14.Gibson L., Holmgreen S.P., Huang D.C.S., Bernard O., Copeland N.G., Jenkins N.A., Sutherland G.R., Baker E., Adams J.M., Cory S. Bcl-W, a novel member of the Bcl-2 family, promotes cell survival. Oncogene. 1996;13:665–675. [PubMed] [Google Scholar]
  • 15.Rosse T., Olivier R., Monney L., Rager M., Conus S., Fellay I., Jansen B., Borner C. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature. 1989;391:496–499. doi: 10.1038/35160. [DOI] [PubMed] [Google Scholar]
  • 16.Jason P., Alejandro S.A. Cell Turnover and Adult Tissue Homeostasis: From Humans to Planarians. Annual Review of Genetics. 2007;41:83–105. doi: 10.1146/annurev.genet.41.110306.130244. [DOI] [PubMed] [Google Scholar]

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