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Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F(1) Mice.

ABSTRACT: 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 B6C3F(1) 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 B6C3F(1) mice. However, AZT-mediated hematologic toxicity appeared to be greater in females compared to males.

SUBMITTER: Desai VG

PROVIDER: S-EPMC3321529 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F(1) Mice.

Desai Varsha G VG Lee Taewon T Moland Carrie L CL Branham William S WS Mittelstaedt Roberta A RA Lewis Sherry M SM Leakey Julian E A JE Fuscoe James C JC

AIDS research and treatment 20120401

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 B6C3F(1) 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-relate ...[more]

PMID: 22545210

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Project description:BackgroundThe occurrence of variations in routine hematological parameters is closely associated with disease progression, the development of severe illness, and the mortality rate among COVID-19 patients. This study aimed to investigate hematological parameters in COVID-19 hospitalized patients from the 1st to the 5th waves of the current pandemic.MethodsThis cross-sectional study included a total of 1501 hospitalized patients with laboratory-confirmed COVID-19 based on WHO criteria, who were admitted to Shahid Sadoughi Hospital (SSH) in Yazd, Iran, from February 2020 to September 2021. Throughout, we encountered five COVID-19 surge waves. In each wave, we randomly selected approximately 300 patients and categorized them based on infection severity during their hospitalization, including partial recovery, full recovery, and death. Finally, hematological parameters were compared based on age, gender, pandemic waves, and outcomes using the Mann-Whitney U and Kruskal-Wallis tests.ResultsThe mean age of patients (n = 1501) was 61.1±21.88, with 816 (54.3%) of them being men. The highest mortality in this study was related to the third wave of COVID-19 with 21.3%. There was a significant difference in all of the hematological parameters, except PDW, PLT, and RDW-CV, among pandemic waves of COVID-19 in our population. The highest rise in the levels of MCV and RDW-CV occurred in the 1st wave, in the 2nd wave for lymphocyte count, MCHC, PLT count, and RDW-SD, in the 3rd wave for WBC, RBC, neutrophil count, MCH, and PDW, and in the 4th wave for Hb, Hct, and ESR (p < 0.01). The median level of Hct, Hb, RBC, and ESR parameters were significantly higher, while the mean level of lymphocyte and were lower in men than in women (p < 0.001). Also, the mean neutrophil in deceased patients significantly was higher than in those with full recovered or partial recovery (p < 0.001).ConclusionThe findings of our study unveiled notable variations in hematological parameters across different pandemic waves, gender, and clinical outcomes. These findings indicate that the behavior of different strains of the COVID-19 may differ across various stages of the pandemic.

Dataset Information

Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F(1) Mice.

Publications

Evaluation of Hepatic Mitochondria and Hematological Parameters in Zidovudine-Treated B6C3F(1) Mice.

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