Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals

Anusha Ande, Carole McArthur, Leo Ayuk, Charles Awasom, Paul Ngang Achu, Annette Njinda, Namita Sinha, P. S.S. Rao, Marisela Agudelo, Anantha Ram Nookala, Stephen Simon, Anil Kumar, Santosh Kumar

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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-tomoderate 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.

Original languageEnglish (US)
Article numbere0122402
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 16 2015

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Oxidative stress
viral load
Viral Load
cytochrome P-450
Cytochrome P-450 Enzyme System
Oxidative Stress
cytokines
oxidative stress
Smoking
HIV
Cytokines
enzymes
Plasmas
monocytes
Antioxidants
substance abuse
antioxidants
Cytochrome P-450 CYP3A
therapeutics
smoking (habit)

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals. / Ande, Anusha; McArthur, Carole; Ayuk, Leo; Awasom, Charles; Achu, Paul Ngang; Njinda, Annette; Sinha, Namita; Rao, P. S.S.; Agudelo, Marisela; Nookala, Anantha Ram; Simon, Stephen; Kumar, Anil; Kumar, Santosh.

In: PloS one, Vol. 10, No. 4, e0122402, 16.04.2015.

Research output: Contribution to journalArticle

Ande, A, McArthur, C, Ayuk, L, Awasom, C, Achu, PN, Njinda, A, Sinha, N, Rao, PSS, Agudelo, M, Nookala, AR, Simon, S, Kumar, A & Kumar, S 2015, 'Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals', PloS one, vol. 10, no. 4, e0122402. https://doi.org/10.1371/journal.pone.0122402
Ande, Anusha ; McArthur, Carole ; Ayuk, Leo ; Awasom, Charles ; Achu, Paul Ngang ; Njinda, Annette ; Sinha, Namita ; Rao, P. S.S. ; Agudelo, Marisela ; Nookala, Anantha Ram ; Simon, Stephen ; Kumar, Anil ; Kumar, Santosh. / Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals. In: PloS one. 2015 ; Vol. 10, No. 4.
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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-tomoderate 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.",
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AU - Sinha, Namita

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