Mitochondrial and Metabolic Effects of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in Mice Receiving One of Five Single- and Three Dual-NRTI Treatments

Antimicrobial Agents and Chemotherapy

Volumn 47, Issue 11, 2003, Pages 3384-3392

  Note, Reine ^a   Maisonneuve, Caroline ^a   Lettéron, Philippe ^a   Peytavin, Gilles ^b   Djouadi, Fatima ^c   Igoudjil, Anissa ^a   Guimont, Marie Christine ^a   Biour, Michel ^d   Pessayre, Dominique ^a   Fromenty, Bernard ^a  

^a BEAUJON HOSPITAL   (France)

^b BICHAT HOSPITAL   (France)

^c HÔPITAL NECKER ENFANTS MALADES   (France)

^d HÔPITAL SAINT ANTOINE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 2 METHYLPROPIONIC ACID; CARNITINE PALMITOYLTRANSFERASE; DIDANOSINE; LAMIVUDINE; MITOCHONDRIAL DNA; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; ZALCITABINE; ZIDOVUDINE;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN TISSUE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; FATTY ACID OXIDATION; HEART; LACTATE BLOOD LEVEL; LIPID METABOLISM; MALE; MITOCHONDRIAL RESPIRATION; MOUSE; MUSCLE TISSUE; NONHUMAN; PRIORITY JOURNAL;

AMINOISOBUTYRIC ACIDS; ANIMALS; BLOTTING, NORTHERN; CHOLESTEROL; DNA; FATTY ACIDS; IMMUNOBLOTTING; KETONE BODIES; LACTIC ACID; LIPID METABOLISM; LIVER; MALE; METABOLISM; MICE; MITOCHONDRIA; OXIDATION-REDUCTION; PHOSPHOLIPIDS; PYRUVIC ACID; REVERSE TRANSCRIPTASE INHIBITORS; THYMIDINE; TRIGLYCERIDES; ZIDOVUDINE;

EID: 10744220267     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.47.11.3384-3392.2003     Document Type: Article

References (52)

1. 14C] thymidine in mice. J. Pharmacol. Exp. Ther. 257:479-486.
2. Barile, M., D. Valenti, S. Passarella, and E. Quagliariello. 1997. 3′-Azido-3′-deoxythymidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator. Biochem. Pharmacol. 53:913-920.
3. Bastard, J. P., M. Caron, H. Vidal, V. Jan, M. Auclair, C. Vigouroux, J. Luboinski, M. Laville, M. Maachi, P. M. Girard, W. Rozenbaum, P. Levan, and J. Capeau. 2002. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 359:1026-1031.
4. Birkus, G., M. J. M. Hitchcock, and T. Cihlar. 2002. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 46:716-723.
5. Brinkman, K., H. J. M. ter Hofstede, D. M. Burger, J. A. Smeitink, and P. P. Koopmans. 1998. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 12:1735-1744.
6. Brinkman, K., J. A. Smeitink, J. A. Romijn, and P. Reiss. 1999. Hypothesis: mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 354:1112-1115.
7. Brivet, F. G., I. Nion, B. Mégarbane, S. Abdelhamid, M. Brivet, P. Rustin, and A. Munnich. 2000. Fatal lactic acidosis and liver steatosis associated with didanosine and stavudine treatment: a respiratory chain dysfunction? J. Hepatol. 32:364-365.
8. Brown, N. F., J. K. Hill, V. Esser, J. L. Kirldand, B. E. Corkey, D. W. Foster, and J. D. McGarry. 1997. Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation: inter-tissue and inter-species expression of CPT I and CPT II enzymes. Biochem. J. 327:225-231.
9. Burcham, P. C., and A. W. Harman. 1991. Acetaminophen toxicity results in site-specific mitochondrial damage in isolated mouse hepatocytes. J. Biol. Chem. 266:5049-5054.
10. Burger, D. M., H. Rosing, R. van Gijn, P. L. Meenhorst, O. van Tellingen, and J. H. Beijnen. 1992. Determination of stavudine, a new antiretroviral agent, in human plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection. J. Chromatogr. 584:239-247.
11. Carpenter, C. C., D. A. Cooper, M. A. Fischl, J. M. Gatell, B. G. Gazzard, S. M. Hammer, M. S. Hirsch, D. M. Jacobsen, D. A. Katzenstein, J. S. Montaner, D. D. Richman, M. S. Saag, M. Schechter, R. T. Schooley, M. A. Thompson, S. Vella, P. G. Yeni, and P. A. Volberding. 2000. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA 283:381-390.
12. Carr, A., and D. A. Cooper. 2000. Adverse effects of antiretroviral therapy. Lancet 356:1423-1430.
13. Chariot, P., I. Drogou, I. de Lacroix-Szmania, M. C. Eliezer-Vanerot, B. Chazaud, A. Lombès, A. Schaeffer, and E. S. Zafrani. 1999. Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. J. Hepatol. 30:156-160.
14. Chêne, G., E. Angelini, L. Cotte, J. M. Lang, P. Morlat, C. Rancinan, T. May, V. Journot, F. Raffi, B. Jarrousse, M. Grappin, G. Lepeu, and J. M. Molina. 2002. Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 34:649-657.
15. Cherry, C. L., M. E. Gahan, J. C. McArthur, S. R. Lewin, J. F. Hoy, and S. L. Wesselingh. 2002. Exposure to dideoxynucleosides is reflected in lowered mitochondrial DNA in subcutaneous fat. J. Acquir. Immune Defic. Syndr. 30:271-277.
16. Chomczynski, P., and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156-159.
17. Clark, S. J., S. Creighton, B. Portmann, C. Taylor, J. A. Wendon, and M. E. Cramp. 2002. Acute liver failure associated with antiretroviral treatment for HIV: a report of six cases. J. Hepatol. 36:295-301.
18. Côté, H. C. F., Z. L. Brumme, K. J. P. Craib, C. S. Alexander, B. Wynhoven, L. Ting, H. Wong, M. Harris, R. Harrigan, M. O'Shaughnessy, and J. S. G. Montaner. 2002. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N. Engl. J. Med. 346:811-820.
19. Cretton, E. M., Z. Zhou, L. B. Kidd, H. M. McClure, S. Kaul, M. J. M. Hitchcock, and J.-P. Sommadossi. 1993. In vitro and in vivo disposition and metabolism of 3′-deoxy-2′,3′-didehydrothymidine. Antimicrob. Agents Chemother. 37:1816-1825.
20. de Martino, M., E. Zammarchi, L. Filippi, M. A. Donati, F. Mannelli, L. Galli, and A. Vierucci. 1995. Redox potential status in children with perinatal HIV-1 infection treated with zidovudine. AIDS 9:1381-1383.
21. Demeilliers, C., C. Maisonneuve, A. Grodet, A. Mansouri, R. Nguyen, M. Tinel, P. Lettéron, C. Degott, G. Feldmann, D. Pessayre, and B. Fromenty. 2002. Impaired adaptive resynthesis and prolonged depletion of hepatic mitochondrial DNA after repeated alcohol binges in mice. Gastroenterology 123:1278-1290.
22. Djouadi, F., C. J. Weinheimer, J. E. Saffitz, C. Pitchford, J. Bastin, F. J. Gonzalez, and D. P. Kelly. 1998. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor α-deficient mice. J. Clin. Investig. 102:1083-1091.
23. Drynan, L., P. A. Quant, and V. A. Zammit. 1996. The role of changes in the sensitivity of hepatic mitochondrial overt carnitine palmitoyltransferase in determining the onset of the ketosis of starvation in the rat. Biochem. J. 318:767-770.
24. Ducluzeau, P. H., A. Lachaux, R. Bouvier, N. Streichenberger, G. Stepien, and B. Mousson. 1999. Depletion of mitochondrial DNA associated with infantile cholestasis and progressive liver fibrosis. J. Hepatol. 30:149-155.
25. Ducluzeau, P. H., A. Lachaux, R. Bouvier, H. Duborjal, G. Stepien, D. Bozon, and B. Mousson de Camaret. 2002. Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. J. Hepatol. 36:698-703.
26. Fellay, J., K. Boubaker, B. Ledergerber, E. Bernasconi, H. Furrer, M. Battegay, B. Hirschel, P. Vernazza, P. Francioli, G. Greub, M. Flepp, and A. Telenti. 2001. Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV cohort study. Lancet 358:1322-1327.
27. Fromenty, B., C. Fisch, A. Berson, P. Lettéron, D. Larrey, and D. Pessayre. 1990. Dual effect of amiodarone on mitochondrial respiration: initial protonophoric uncoupling effect followed by inhibition of the respiratory chain at the levels of complex I and complex II. J. Pharmacol. Exp. Ther. 255:1377-1384.
28. Fromenty, B., C. Fish, G. Labbe, C. Degott, D. Deshamps, A. Berson, P. Lettéron, and D. Pessayre. 1990. Amiodarone inhibits the mitochondrial β-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. J. Pharmacol. Exp. Ther. 255:1371-1376.
29. Fromenty, B., E. Fréneaux, G. Labbe, D. Deschamps, D. Larrey, P. Lettéron, and D. Pessayre. 1989. Tianeptine, a new tricyclic antidepressant metabolized by β-oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice. Biochem. Pharmacol. 38:3743-3751.
30. Fromenty, B., S. Grimbert, A. Mansouri, M. Beaugrand, S. Erlinger, A. Rötig, and D. Pessayre. 1995. Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis. Gastroenterology 108:193-200.
31. Fromenty, B., P. Lettéron, C. Fish, A. Berson, D. Deschamps, and D. Pessayre. 1993. Evaluation of human blood lymphocytes as a model to study the effects of drugs on human mitochondria. Effects of low concentrations of amiodarone on fatty acid oxidation, ATP levels and cell survival. Biochem. Pharmacol. 46:421-432.
32. Fromenty, B., and D. Pessayre. 1995. Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol. Ther. 67:101-154.
33. Gaou, I., M. Malliti, M. C. Guimont, P. Lettéron, C. Demeilliers, G. Peytavin, C. Degott, D. Pessayre, and B. Fromenty. 2001. Effect of stavudine on mitochondrial genome and fatty acid oxidation in lean and obese mice. J. Pharmacol. Exp. Ther. 297:516-523.
34. Jacotot, E., L. Ravagnan, M. Loeffler, K. F. Ferri, H. L. A. Vieira, N. Zamzami, P. Costantini, S. Druillennec, J. Hoebeke, J. P. Brland, T. Irinopoulou, E. Daugas, S. A. Susin, D. Cointe, Z. H. Xie, J. C. Reed, B. P. Roques, and G. Kroemer. 2000. The HIV-viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J. Exp. Med. 191:33-45.
35. John, M., C. B. Moore, I. R. James, D. Nolan, R. P. Upton, E. J. McKinnon, and S. A. Mallal. 2001. Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy. AIDS 15:717-723.
36. Kersten, S., J. Seydoux, J. M. Peters, F. J. Gonzales, B. Desvergne, and W. Wahli. 1999. Peroxisome proliferator-activated receptor α mediates the adaptive response to fasting. J. Clin. Investig. 103:1489-1498.
37. Lewis, W., and M. C. Dalakas. 1995. Mitochondrial toxicity of antiviral drugs. Nat. Med. 1:417-422.
38. Lewis, W., C. P. Haase, S. M. Raidel, R. B. Russ, R. L. Sutliff, B. D. Holt, and A. M. Samarel. 2001. Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice. Lab. Investig. 81:1527-1536.
39. Mansouri, A., I. Gaou, C. De Kerguenec, S. Amsellem, D. Haouzi, A. Berson, A. Moreau, G. Feldmann, P. Lettéron, D. Pessayre, and B. Fromenty. 1999. An alcoholic binge causes massive degradation of hepatic mitochondrial DNA in mice. Gastroenterology 117:181-190.
40. McGarry, J. D., and D. W. Foster. 1980. Regulation of hepatic fatty acid oxidation and ketone body production. Annu. Rev. Biochem. 49:395-420.
41. Nicolas, F., G. De Sousa, P. Thomas, M. Placidi, G. Lorenzon, and R. Rahmani. 1995. Comparative metabolism of 3′-azido-3′-deoxythymidine in cultured hepatocytes from rats, dogs, monkeys, and humans. Drug Metab. Dispos. 23:308-313.
42. Nolan, D., M. John, and S. Mallal. 2001. Antiretroviral therapy and the lipodystrophy syndrome, part 2: concepts in aetiopathogenesis. Antivir. Ther. 6:145-160.
43. Pan-Zhou, X.-R., L. Cui, X.-J. Zhou, J.-P. Sommadossi, and V. M. Darley-Usmar. 2000. Differential effects of antiretroviral nucleoside analogs on mitochondrial function in HepG2 cells. Antimicrob. Agents Chemother. 44:496-503.
44. Patterson, T. A., Z. K. Binienda, G. D. Newport, G. W. Lipe, M. P. Gillam, W. Slikker, and J. A. Sandberg. 2000. Transplacental pharmacokinetics and fetal distribution of 2′, 3′-didehydro-3′-deoxythymidine (d4T) and its metabolites in late-term rhesus macaques. Teratology 62:93-99.
45. Petit, F., D. Arnoult, J.-D. Lelièvre, L. Moutouh-de Parseval, A. J. Hance, P. Schneider, J. Corbeil, J. C. Ameisen, and J. Estaquier. 2002. Productive HIV-1 infection of primary CD4+ T cells induces mitochondrial membrane permeabilization leading to a caspase-independent cell death. J. Biol. Chem. 277:1477-1487.
46. Riddle, T. M., D. G. Kuhel, L. A. Woollett, C. J. Fichtenbaum, and D. Y. Hui. 2001. HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to accumulation of activated sterol regulatory element-binding proteins in the nucleus. J. Biol. Chem. 276:37514-37519.
47. Roche, R., I. Poizot-Martin, C. Martin-El Yazidi, E. Compe, J. A. Gastaut, J. Torresani, and R. Planells. 2002. Effects of antiretroviral drug combinations on the differentiation of adipocytes. AIDS 16:13-20.
48. Shaer, A. J., and A. Rastegar. 2000. Lactic acidosis in the setting of antiretroviral therapy for the acquired immunodeficiency syndrome: a case report and review of the literature. Am. J. Nephrol. 20:332-338.
49. Shaikh, S., C. Ta, A. A. Basham, and S. Mansour. 2001. Leber hereditary optic neuropathy associated with antiretroviral therapy for human immunodeficiency virus infection. Am. J. Ophthalmol. 131:143-145.
50. Thupari, J. N., L. E. Landree, G. V. Ronnett, and F. P. Kuhajda. 2002. C57 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc. Natl. Acad. Sci. USA 99:9498-9502.
51. Touati, G., O. Rigal, A. Lombès, P. Frachon, M. Giraud, and H. Ogier de Baulny. 1997. In vivo functional investigations of lactic acid in patients with respiratory chain disorders. Arch. Dis. Child 76:16-21.
52. Walker, U. A., M. Bickel, S. I. Lütke Volksbeck, U.-P. Ketelsen, H. Schöfer, B. Setzer, N. Venhoff, V. Rickerts, and S. Staszewski. 2002. Evidence of nucleoside analogue reverse transcriptase inhibitor-associated genetic and structural defects of mitochondria in adipose tissue of HIV-infected patients. J. Acquir. Immune Defic. Syndr. 29:117-121.