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AIDS Research and Treatment
Volume 2012 (2012), Article ID 317695, 8 pages
http://dx.doi.org/10.1155/2012/317695
Research Article

Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated Mice

1Division of Systems Biology, Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA
2Department of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700, Republic of Korea
3Division of Genetic and Molecular Toxicology, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA
4Office of Scientific Coordination, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA

Received 28 November 2011; Accepted 12 January 2012

Academic Editor: Robert R. Redfield

Copyright © 2012 Varsha G. Desai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. T. Dieterich, “Long-term complications of nucleoside reverse transcriptase inhibitor therapy,” AIDS Reader, vol. 13, no. 4, pp. 176–187, 2003. View at Scopus
  2. J. S. Currier, C. Spino, J. Grimes et al., “Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection,” Journal of Acquired Immune Deficiency Syndromes, vol. 24, no. 4, pp. 316–324, 2000.
  3. I. Ofotokun and C. Pomeroy, “Sex differences in adverse reactions to antiretroviral drugs,” Top HIV Med, vol. 11, no. 2, pp. 55–59, 2003. View at Scopus
  4. M. Gandhi, F. Aweeka, R. M. Greenblatt, and T. F. Blaschke, “Sex differences in pharmacokinetics and pharmacodynamics,” Annual Review of Pharmacology and Toxicology, vol. 44, pp. 499–523, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Ofotokun, “Sex differences in the pharmacologic effects of antiretroviral drugs: potential roles of drug transporters and phase 1 and 2 metabolizing enzymes,” Topics in HIV Medicine, vol. 13, no. 2, pp. 79–83, 2005. View at Scopus
  6. H. Lee, J. Hanes, and K. A. Johnson, “Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase,” Biochemistry, vol. 42, no. 50, pp. 14711–14719, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. J. J. Kohler and W. Lewis, “A brief overview of mechanisms of mitochondrial toxicity from NRTIs,” Environmental and Molecular Mutagenesis, vol. 48, no. 3-4, pp. 166–172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. C. L. Cherry, D. Nolan, I. R. James et al., “Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-infected individuals,” Journal of Acquired Immune Deficiency Syndromes, vol. 42, no. 4, pp. 435–440, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. R. L. Divi, T. L. Einem, S. L. L. Fletcher et al., “Progressive mitochondrial compromise in brains and livers of primates exposed in utero to nucleoside reverse transcriptase inhibitors (NRTIs),” Toxicological Sciences, vol. 118, no. 1, pp. 191–201, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Gerschenson, S. W. Erhart, C. Y. Paik et al., “Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3′-azido-3′-deoxythymidine,” AIDS Research and Human Retroviruses, vol. 16, no. 7, pp. 635–644, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. S. M. Torres, R. L. Divi, D. M. Walker et al., “In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue,” Cardiovascular Toxicology, vol. 10, no. 2, pp. 87–99, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. K. C. Lund and K. B. Wallace, “Direct, DNA pol-γ-independent effects of nucleoside reverse transcriptase inhibitors on mitochondrial bioenergetics,” Cardiovascular Toxicology, vol. 4, no. 3, pp. 217–228, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. V. G. Desai, T. Lee, R. R. Delongchamp et al., “Nucleoside reverse transcriptase inhibitors (NRTIs)-induced expression profile of mitochondria-related genes in the mouse liver,” Mitochondrion, vol. 8, no. 2, pp. 181–195, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. R. Geddes, S. Knight, M. Y. S. Moosa, A. Reddi, K. Uebel, and H. Sunpath, “A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context,” South African Medical Journal, vol. 96, no. 8, pp. 722–724, 2006. View at Scopus
  15. C. W. Wester, O. A. Okezie, A. M. Thomas et al., “Higher-than-expected rates of lactic acidosis among highly active antiretroviral therapy-treated women in Botswana: preliminary results from a large randomized clinical trial,” Journal of Acquired Immune Deficiency Syndromes, vol. 46, no. 3, pp. 318–322, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. R. Justo, J. Boada, M. Frontera, J. Oliver, J. Bermúdez, and M. Gianotti, “Gender dimorphism in rat liver mitochondrial oxidative metabolism and biogenesis,” American Journal of Physiology, vol. 289, no. 2, pp. C372–C378, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. G. Moyle, “Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity,” AIDS Reviews, vol. 4, no. 1, pp. 13–20, 2002. View at Scopus
  18. A. Sharma, R. Vora, M. Modi, A. Sharma, and Y. Marfatia, “Adverse effects of antiretroviral treatment,” Indian Journal of Dermatology, Venereology and Leprology, vol. 74, no. 3, pp. 234–237, 2008.
  19. Center for Disease Control (CDC) and Prevention, Public Health Services Task Force. Recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States, 2008, http://www.aidsinfo.nih.gov/guidelines/.
  20. V. G. Desai, T. Lee, R. R. Delongchamp et al., “Development of mitochondria-specific mouse oligonucleotide microarray and validation of data by real-time PCR,” Mitochondrion, vol. 7, no. 5, pp. 322–329, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Delongchamp, T. Lee, and C. Velasco, “A method for computing the overall statistical significance of a treatment effect among a group of genes,” BMC Bioinformatics, vol. 7, supplement 2, article S11, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. M. B. Myers, R. A. Mittelstaedt, and R. H. Heflich, “Using ΦX174 DNA as an exogenous reference for measuring mitochondrial DNA copy number,” BioTechniques, vol. 47, no. 4, pp. 867–869, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Matsushita, K. Yoshimura, T. Kimura et al., “Spontaneous recovery of hemoglobin and neutrophil levels in Japanese patients on a long-term Combivir® containing regimen,” Journal of Clinical Virology, vol. 33, no. 3, pp. 188–193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. D. Mildvan, T. Creagh, and G. Leitz, “Prevalence of anemia and correlation with biomarkers and specific antiretroviral regimens in 9690 human immunodeficiency virus-infected patients: findings of the Anemia Prevalence Study,” Current Medical Research and Opinion, vol. 23, no. 2, pp. 343–355, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. M. I. Luster, G. J. Rosenthal, W. Cao et al., “Experimental studies of the hematologic and immune system toxicity of nucleoside derivatives used against HIV infection,” International Journal of Immunopharmacology, vol. 13, supplement 1, pp. 99–107, 1991. View at Publisher · View at Google Scholar · View at Scopus
  27. M. B. Thompson, J. K. Dunnick, M. E. Sutphin, H. D. Giles, R. D. Irwin, and J. D. Prejean, “Hematologic toxicity of AZT and ddC administered as single agents and in combination to rats and mice,” Fundamental and Applied Toxicology, vol. 17, no. 1, pp. 159–176, 1991. View at Publisher · View at Google Scholar · View at Scopus
  28. National Institute of Environmental Health Sciences, “NIEHS technical report on the 13-week toxicity study of 3-Azido-3-deoxythymidine (AZT) and Isoniazid combinations administered by gavage to B6C3F1 mice,” NIEHS AIDS Therapeutics Toxicity Report no. 8, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health Research, Triangle Park, NC, USA, 2002.
  29. M. Laguno, A. Milinkovic, E. De Lazzari, et al., “Incidence and risk factors for mitochondrial toxicity in treated HIV/HCV-coinfected patients,” Antiviral Therapy, vol. 10, no. 3, pp. 423–429, 2005. View at Scopus
  30. J. A. Dykens, J. Jamieson, L. Marroquin, S. Nadanaciva, P. A. Billis, and Y. Will, “Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro,” Toxicology and Applied Pharmacology, vol. 233, no. 2, pp. 203–210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. C. Wei, W. X. Zong, E. H. Y. Cheng et al., “Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death,” Science, vol. 292, no. 5517, pp. 727–730, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. E. Y. Tan, L. Campo, C. Han et al., “BNIP3 as a progression marker in primary human breast cancer opposing functions in in situ versus invasive cancer,” Clinical Cancer Research, vol. 13, no. 2, pp. 467–474, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. J. L. Fang and F. A. Beland, “Long-term exposure to zidovudine delays cell cycle progression, induces apoptosis, and decreases telomerase activity in human hepatocytes,” Toxicological Sciences, vol. 111, no. 1, pp. 120–130, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. D. J. Hooker and C. L. Cherry, “Apoptosis: a clinically useful measure of antiretroviral drug toxicity? Apoptosis: a clinically useful measure of antiretroviral drug toxicity? Hooker & Cherry,” Expert Opinion on Drug Metabolism and Toxicology, vol. 5, no. 12, pp. 1543–1553, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. L. Day, C. Shikuma, and M. Gerschenson, “Mitochondrial injury in the pathogenesis of antiretroviral-induced hepatic steatosis and lactic acidemia,” Mitochondrion, vol. 4, no. 2-3, pp. 95–109, 2004. View at Publisher · View at Google Scholar · View at Scopus