Abstract
In the present study, we investigated the ability of anti-HIV drugs to interfere with normal cell cycle progression and to induce oxidative stress by perturbing the redox environment. Our results provide evidence that anti-HIV drugs have a differential effect on adipocyte cell cycle and differentiation, being able to modify the response to oxidative stress through an increase of reactive oxygen species (ROS) that compromises the induction of phase-2 and antioxidant enzymes. In detail, saquinavir, efavirenz, and stavudine exert antiadipogenic influences on the model 3T3-L1 cell line, perturbing the oxidative response and inducing of apoptosis. When considered together, the effects of anti-HIV drugs on 3T3-L1 pre adipocytes are distinct but commonly antiadipogenic, thus suggesting another additional possible mechanism by which antiretroviral therapies could contribute to lipoatrophy.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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3T3-L1 Cells / drug effects
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3T3-L1 Cells / metabolism
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Adipocytes / drug effects*
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Adipocytes / pathology
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Adipogenesis / drug effects*
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Alkynes
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Animals
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Anti-HIV Agents / pharmacology*
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Apoptosis / drug effects*
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Benzoxazines / pharmacology
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Carbamates / pharmacology
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Cell Cycle / drug effects
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Cyclopropanes
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Dexamethasone / pharmacology
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Enzyme Induction / drug effects
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Furans
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HIV-Associated Lipodystrophy Syndrome / chemically induced
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HIV-Associated Lipodystrophy Syndrome / pathology
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Heme Oxygenase-1 / biosynthesis
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Heme Oxygenase-1 / genetics
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Indinavir / pharmacology
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Insulin / pharmacology
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Mice
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NAD(P)H Dehydrogenase (Quinone) / biosynthesis
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NAD(P)H Dehydrogenase (Quinone) / genetics
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Oxidation-Reduction
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Oxidative Stress
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Reactive Oxygen Species / metabolism
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Real-Time Polymerase Chain Reaction
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Saquinavir / pharmacology
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Stavudine / pharmacology
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Sulfonamides / pharmacology
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Superoxide Dismutase / biosynthesis
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Superoxide Dismutase / genetics
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Superoxide Dismutase-1
Substances
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Alkynes
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Anti-HIV Agents
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Benzoxazines
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Carbamates
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Cyclopropanes
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Furans
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Insulin
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Membrane Proteins
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Reactive Oxygen Species
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SOD1 protein, human
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Sulfonamides
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amprenavir
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Indinavir
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Dexamethasone
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Stavudine
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1
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NAD(P)H Dehydrogenase (Quinone)
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Nqo1 protein, mouse
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efavirenz
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Saquinavir
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1-Methyl-3-isobutylxanthine