High doses of stavudine induce fat wasting and mild liver damage without impairing mitochondrial respiration in mice

Antiviral Therapy

Volumn 12, Issue 3, 2007, Pages 389-400

  Igoudjil, Anissa ^a   Abbey Toby, Adjé ^b   Begriche, Karima ^a   Grodet, Alain ^a   Chataigner, Karine ^a   Peytavin, Gilles ^c   Maachi, Mustapha ^d   Colin, Marion ^a   Robin, Marie Anne ^a   Lettéron, Philippe ^a   Feldmann, Gérard ^a   Pessayre, Dominique ^a   Fromenty, Bernard ^a  

^a CENTRE DE RECHERCHE BIOMÉDICALE BICHAT BEAUJON CRB3   (France)

^b BEAUJON HOSPITAL   (France)

^c BICHAT HOSPITAL   (France)

^d HÔPITAL TENON   (France)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 2 METHYLPROPIONIC ACID; ACYL COENZYME A DESATURASE; AMINOTRANSFERASE; CARNITINE; KETONE BODY; LACTIC ACID; LEPTIN; LEVOCARNIL; STAVUDINE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD ANALYSIS; BODY FAT; CELL STRUCTURE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG MEGADOSE; DUAL ENERGY X RAY ABSORPTIOMETRY; FATTY ACID OXIDATION; LACTATE BLOOD LEVEL; LIVER; LIVER CELL; LIVER INJURY; MALE; MITOCHONDRIAL RESPIRATION; MOUSE; MUSCLE TISSUE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TREATMENT DURATION; WHITE ADIPOSE TISSUE;

ADIPOSE TISSUE, WHITE; ADMINISTRATION, ORAL; AMINOISOBUTYRIC ACIDS; ANIMALS; CARNITINE; FATTY ACIDS; HEPATOCYTES; KETONE BODIES; LEPTIN; LIPODYSTROPHY; LIVER; LIVER DISEASES; MALE; MICE; MITOCHONDRIA, LIVER; REVERSE TRANSCRIPTASE INHIBITORS; STAVUDINE; STEAROYL-COA DESATURASE; TRANSAMINASES; VITAMIN B COMPLEX; WASTING SYNDROME;

EID: 34249081852     PISSN: 13596535     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (43)

1. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chriholm D, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353:2093-2099.
2. Bastard JP, Caron M, Vidal H, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 2002; 359:1026-1031.
3. Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidemia and liver dysfunction with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 2000; 14:F25-F32.
4. Sutinen J, Häkkinen AM, Westerbacka J, et al. Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy. AIDS 2002; 16:2183-2193.
5. Gougeon ML, Penicaud L, Fromenty B, Leclercq P, Viard JP, Capeau J. Adipocytes targets and actors in the pathogenesis of HIV-associated lipodystrophy and metabolic alterations. Antivir Ther 2004; 9:161-177.
6. Saint-Marc T, Partisani M, Poizot-Martin I, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 1999; 13:1659-1667.
7. Mallal SA, John M, Moore CB, James IR, McKinnon EJ. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 2000; 14:1309-1316.
8. Sánchez-Conde M, de Mendoza C, Jiménez-Nacher I, Barreiro P, Gonzalez-Lahoz J, Soriano V. Reductions in stavudine dose might ameliorate mitochondrial-associated complications without compromising antiviral activity. HIV Clin Trials 2005; 6:197-202.
9. th European AIDS Conference/EACS. 17-20 November 2005, Dublin, Ireland. Abstract PE7.3/19.
10. Fromenty B, Pessayre D. Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol Ther 1995; 67:101-154.
11. Brinkman K, ter Hofstede HJM, Burger DM, Smeitink JA, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998; 12:1735-1744.
12. Igoudjil A, Begriche K, Pessayre D, Fromenty B. Mitochondrial, metabolic and genotoxic effects of antiretroviral nucleoside reverse-transcriptase inhibitors. Anti-infect Agents Med Chem 2006; 5:273-292.
13. Walker UA, Bauerle J, Laguno M, et al. Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine. Hepatology 2004; 39:311-317.
14. Nolan D, Hammond E, Martin A, et al. Mitochondrial depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy. AIDS 2003; 17:1329-1338.
15. Barile M, Valenti D, Passarella S, Quagliariello E. 3′-Azido- 3′-deoxythymidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator. Biochem Pharmacol 1997; 53:913-920.
16. Maisonneuve C, Igoudjil A, Begriche K, et al. Effects of zidovudine, stavudine and β-aminoisobutyric acid on lipid homeostasis in mice : possible role in human fat wasting. Antivir Ther 2004; 9:803-812.
17. Note R, Maisonneuve C, Lettéron P, et al. Mitochondrial and metabolic effects of nucleoside reverse transcriptase inhibitors (NRTIs) in mice receiving one of five single- and three- dual-NRTI treatments. Antimicrob Agents Chemother 2003; 47:3384-3392.
18. Fromenty B, Fish C, Labbe G, et al. Amiodarone inhibits the mitochondrial β-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. J Pharmacol Exp Ther 1990; 255:1371-1376.
19. Gaou I, Malliti M, Guimont MC, et al. Effect of stavudine on mitochondrial genome and fatty acid oxidation in lean and obese mice. J Pharmacol Exp Ther 2001; 297:516-523.
20. Malgat M, Durrieu G, Mazat JP. Enzymatic and polarographic measurements of the respiratory chain complexes. In Mitochondrial Diseases: Models and Methods, 1999; pp. 357-377. Edited by P Lestienne. Paris: Springer Verlag.
21. Attoub S, Levasseur S, Buyse M, et al. Physiological role of cholecystokinin B/gastrin receptor in leptin secretion. Endocrinology 1999; 140:4406-4410.
22. de Sousa C, English NR, Stacey TE, Chalmers RA. Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults. Clin Chim Acta 1990; 187:317-328.
23. Robin MA, Demeilliers C, Sutton A, et al. Alcohol increases tumor necrosis factors α and decreases nuclear factor-κB to activate hepatic apoptosis in genetically obese mice. Hepatology 2005; 42:1280-1290.
24. Rogers PD, Barker KS. Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisiation of azole resistance in Candida albicans clinical isolates. Antimicrob Agents Chemother 2003; 47:1220-1227.
25. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770.
26. Schaff Z, Lapis K. Fine structure of hepatocytes during the etiology of several common pathologies. J Electron Microsc Tech 1990; 14:179-207.
27. Maaswinkel-Mooij PD, Van den Bogert C, Scholte HR, Onkenhout W, Brederoo P, Poorthuis BJH. Depletion of mitochondrial DNA in the liver of a patient with lactic acidemia and hypoketotic hypoglycemia. J Pediatr 1996; 128:679-683.
28. Ducluzeau PH, Lachaux A, Bouvier R, et al. Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. J Hepatol 2002; 36:698-703.
29. Cohen P, Friedman JM. Leptin and the control of metabolism: role for stearoyl-CoA desaturase-1 (SCD-1). J Nutr 2004; 134:2455S-2463S.
30. Dobrzyn P, Dobrzyn A, Miyazaki M, et al. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci U S A 2004; 101:6409-6414.
31. Kaul S, Christofalo B, Raymond RH, Stewart MB, Macleod CM. Effect of food on the bioavailability of stavudine in subjects with human immunodeficiency virus infection. Antimicrob Agents Chemother 1998; 42:2295-2298.
32. van der Valk M, Gisolf EH, Reiss P, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection. AIDS 2001; 15:847-855.
33. Acosta EP, Balfour HH. Intermittent administration of high dose stavudine to nucleoside-experienced individuals infected with HIV-1. J Acquir Immune Defic Syndr 2003; 33:343-348.
34. Asilmaz E, Cohen P, Miyazaki M, et al. Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. J Clin Invest 2004; 113:414-424.
35. Mattacks CA, Sadler D, Pond CM. Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells, and their interaction with dietary lipids. Comp Biochem Physiol C Toxicol Pharmacol 2003; 135:11-29.
36. Lagathu C, Bastard JP, Auclair M, et al. Antiretroviral drugs with adverse effects on adipocyte lipid metabolism and survival alter the expression and secretion of proinflammatory cytokines and adiponectin in vitro. Antiv Ther 2004; 9:911-920.
37. Rodriguez de la Concepcion ML, Yubero P, Domingo JC, et al. Reverse transcriptase inhibitors alter uncoupling protein-1 and mitochondrial biogenesis in brown adipocytes. Antiv Ther 2005; 10:515-526.
38. Deveaud C, Beauvoit B, Hagry S, et al. Site specific alterations of adipose tissue mitochondria in 3′-azido-3′-deoxythymidine (AZT)-treated rats: An early stage in lipodystrophy? Biochem Pharmacol 2005; 70:90-101.
39. Clouet P, Niot I, Bézard J. Pathway of α-linolenic acid through the mitochondrial outer membrane in the rat liver and influence on the rate of oxidation. Comparison with linoleic and oleic acids. Biochem J 1989; 263:867-873.
40. Bykov I, Järveläinen H, Lindros K. L-Carnitine alleviates alcohol-induced liver damage in rats: role of tumour necrosis factor-α. Alcohol Alcohol 2003; 38:400-406.
41. Demirdag K, Bahcecioglu IH, Ozercan IH, Ozden M, Yilmaz S, Kalkan A. Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. J Gastroenterol Hepatol 2004; 19:333-338.
42. Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther 2005; 10 Suppl 2:M117-M123.
43. Velsor LW, Kovacevic M, Goldstein M, Leitner HM, Lewis W, Day BJ. Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine. Toxicol Appl Pharmacol 2004; 199:10-19.