title: Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.
abstract: Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.
authors: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors: Anusha
authors: A
authors: Ande
authors: Department of Oral and Craniofacial Science, School of Dentistry, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors: Carole
authors: C
authors: McArthur
authors: Regional Hospital, Box 818, Bamenda, North West Province, Cameroon.
authors: Leo
authors: L
authors: Ayuk
authors: Regional Hospital, Box 818, Bamenda, North West Province, Cameroon.
authors: Charles
authors: C
authors: Awasom
authors: Mezam Polyclinic HIV/AIDS Treatment Center, Bamenda, Cameroon.
authors: Paul Ngang
authors: PN
authors: Achu
authors: Mezam Polyclinic HIV/AIDS Treatment Center, Bamenda, Cameroon.
authors: Annette
authors: A
authors: Njinda
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors: Namita
authors: N
authors: Sinha
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors: P S S
authors: PS
authors: Rao
authors: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors: Marisela
authors: M
authors: Agudelo
authors: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors: Anantha Ram
authors: AR
authors: Nookala
authors: Department of Medical Informatics, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors: Stephen
authors: S
authors: Simon
authors: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors: Anil
authors: A
authors: Kumar
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors: Santosh
authors: S
authors: Kumar
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012907:Smoking; D019562:Viral Load; D055815:Young Adult
chemical_list: D016207:Cytokines; D003577:Cytochrome P-450 Enzyme System