Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice
The effects of 12-week exposure to zidovudine (AZT) at 400, 500, and 600 mg/kg/d were examined on expression of 542 mitochondria-related genes and mitochondrial DNA (mtDNA) copy number in the liver of male and female B6C3F1 mice to understand mitochondrial role in sex-related differences in developm...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | AIDS Research and Treatment |
| Online Access: | http://dx.doi.org/10.1155/2012/317695 |
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| author | Varsha G. Desai Taewon Lee Carrie L. Moland William S. Branham Roberta A. Mittelstaedt Sherry M. Lewis Julian E. A. Leakey James C. Fuscoe |
| author_facet | Varsha G. Desai Taewon Lee Carrie L. Moland William S. Branham Roberta A. Mittelstaedt Sherry M. Lewis Julian E. A. Leakey James C. Fuscoe |
| author_sort | Varsha G. Desai |
| collection | DOAJ |
| description | The effects of 12-week exposure to zidovudine (AZT) at 400, 500, and 600 mg/kg/d were examined on expression of 542 mitochondria-related genes and mitochondrial DNA (mtDNA) copy number in the liver of male and female B6C3F1 mice to understand mitochondrial role in sex-related differences in development of lactic acidosis. Plasma lactate levels and hematologic parameters were also examined. Results indicated increased red blood cell (RBC) count in vehicle-treated controls, whereas a dose-related decline in the RBC count was noted in AZT-treated mice compared to the basal levels before treatments began. These decreases were associated with significant dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin levels. This effect was greater in AZT-treated females compared to males. In both sexes, 12-week AZT or vehicle exposure significantly reduced plasma lactate levels compared to the basal levels. Results also showed modest, but significant, changes in the expression of genes associated with apoptosis and lipid metabolism at 600 mg/kg/d AZT. Neither drug nor sex influenced hepatic mtDNA copy number. Altogether, 12-week AZT exposure as high as 600 mg/kg/d did not impair hepatic mitochondria or induce lactic acidosis in B6C3F1 mice. However, AZT-mediated hematologic toxicity appeared to be greater in females compared to males. |
| format | Article |
| id | doaj-art-de3287a29a3c45bfb09c952ecd52aa43 |
| institution | Kabale University |
| issn | 2090-1240 2090-1259 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | AIDS Research and Treatment |
| spelling | doaj-art-de3287a29a3c45bfb09c952ecd52aa432025-08-20T03:26:30ZengWileyAIDS Research and Treatment2090-12402090-12592012-01-01201210.1155/2012/317695317695Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 MiceVarsha G. Desai0Taewon Lee1Carrie L. Moland2William S. Branham3Roberta A. Mittelstaedt4Sherry M. Lewis5Julian E. A. Leakey6James C. Fuscoe7Division of Systems Biology, Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USADepartment of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700, Republic of KoreaDivision of Systems Biology, Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USADivision of Systems Biology, Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USADivision of Genetic and Molecular Toxicology, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USAOffice of Scientific Coordination, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USAOffice of Scientific Coordination, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USADivision of Systems Biology, Center for Functional Genomics, U.S. FDA/National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USAThe effects of 12-week exposure to zidovudine (AZT) at 400, 500, and 600 mg/kg/d were examined on expression of 542 mitochondria-related genes and mitochondrial DNA (mtDNA) copy number in the liver of male and female B6C3F1 mice to understand mitochondrial role in sex-related differences in development of lactic acidosis. Plasma lactate levels and hematologic parameters were also examined. Results indicated increased red blood cell (RBC) count in vehicle-treated controls, whereas a dose-related decline in the RBC count was noted in AZT-treated mice compared to the basal levels before treatments began. These decreases were associated with significant dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin levels. This effect was greater in AZT-treated females compared to males. In both sexes, 12-week AZT or vehicle exposure significantly reduced plasma lactate levels compared to the basal levels. Results also showed modest, but significant, changes in the expression of genes associated with apoptosis and lipid metabolism at 600 mg/kg/d AZT. Neither drug nor sex influenced hepatic mtDNA copy number. Altogether, 12-week AZT exposure as high as 600 mg/kg/d did not impair hepatic mitochondria or induce lactic acidosis in B6C3F1 mice. However, AZT-mediated hematologic toxicity appeared to be greater in females compared to males.http://dx.doi.org/10.1155/2012/317695 |
| spellingShingle | Varsha G. Desai Taewon Lee Carrie L. Moland William S. Branham Roberta A. Mittelstaedt Sherry M. Lewis Julian E. A. Leakey James C. Fuscoe Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice AIDS Research and Treatment |
| title | Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice |
| title_full | Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice |
| title_fullStr | Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice |
| title_full_unstemmed | Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice |
| title_short | Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F1 Mice |
| title_sort | evaluation of hepatic mitochondria and hematological parameters in zidovudine treated b6c3f1 mice |
| url | http://dx.doi.org/10.1155/2012/317695 |
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