Mitochondrial disruption and apoptosis in lymphocytes of an HIV infected patient affected by lactic acidosis after treatment with highly active antiretroviral therapy
| Autor: | M Catalano, M Todaro, Manlio Tolomeo, Vincenzo Abbadessa, Giuliana Cannizzo, Eleonora Barbusca, G Stassi, Serenella Arista, Salvatrice Mancuso |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
medicine.medical_specialty Anti-HIV Agents Lymphocyte Apoptosis HIV Infections Case Reports Mitochondrion Biology Pathology and Forensic Medicine chemistry.chemical_compound immune system diseases Indinavir Antiretroviral Therapy Highly Active Internal medicine medicine Humans Lymphocytes Didanosine Acridine orange Stavudine virus diseases General Medicine medicine.disease Mitochondria Endocrinology medicine.anatomical_structure chemistry Lactic acidosis Immunology Acidosis Lactic Female medicine.drug |
| Zdroj: | Journal of Clinical Pathology. 56:147-151 |
| ISSN: | 0021-9746 |
| Popis: | Aims: Highly active antiretroviral therapy (HAART) can induce an increase in lactic acid concentrations that seems to be caused by mitochondrial dysfunction induced by the interaction of nucleoside reverse transcriptase inhibitors (NRTIs) with DNA polymerase γ in the mitochondria. Mitochondrial alterations have been described in liver and muscle cells of NRTI treated human immunodeficiency virus (HIV) infected patients. Because lymphocytes are the main target for HIV and because mitochondria are involved in apoptosis, we studied mitochondrial morphology and apoptosis in the lymphocytes of an HIV infected patient with severe lactic acidosis after treatment with stavudine, didanosine, and indinavir. Methods: The patient was a 39 year old woman. After two years of treatment she developed rapid weight loss with severe fat wasting, peripheral neuropathy, and hyperlacticaemia, which persisted after treatment withdrawal. The numbers and the morphology of the mitochondria were evaluated by electronic microscopy; the percentage of apoptotic cells was calculated by flow cytometry after staining with annexine V and by fluorescent microscopy after staining with ethidium bromide and acridine orange. Results: The numbers of mitochondria in the lymphocytes were greatly decreased when compared with the lymphocytes of healthy individuals. The most important mitochondrial morphological alterations were swelling and the disruption of cristae and internal mitochondrial structure. These alterations were more evident during the period in which lactic acid values were very high. Moreover, a high percentage of apoptotic lymphocytes was seen. Morphological examination conducted one week after the normalisation of lacticaemia showed a pronounced increase in the number of mitochondria. The morphological alterations were no longer evident, although the size of each mitochondrion was smaller than normal. Moreover, the percentage of apoptotic cells was lower than 5%. Conclusions: This report describes important morphological alterations in lymphocyte mitochondria in an HIV infected patient during a severe phase of HAART induced hyperlacticaemia. These alterations persisted for several weeks after treatment withdrawal and were associated with an increase in lymphocyte apoptosis. Considering the important role of mitochondria in the apoptotic pathway, the increase in lymphocyte apoptosis may be a consequence of proapoptotic factors released from altered mitochondria. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|