Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

OBJECTIVES: Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). METHODS: A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. RESULTS: After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. CONCLUSIONS: When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

Endothelin-1 expression during early response after antigen challenge in brown-norway rats.

The objective of this study is to investigate if endothelin-1 (ET-1) gene expression changes during the early response phase following antigen challenge. We used sensitized Brown-Norway rats known to develop an early airway response after antigen challenge. After ovalbumin challenge, sensitized rats presented an early response, characterized by an increase in pulmonary pressure (209+/-14.53%,P<0. 01) and diminished functional parameters (inspiratory capacity, forced vital capacity (FVC) and expiratory flow at 75% of FVC), compared to their respective basal values. ET-1 mRNA expression was assessed by reverse transcription and polymerase chain reaction using specific primers for prepro-ET-1. A group of unsensitized rats was used as control. ET-1 expression was significantly enhanced in sensitized rats during the early response (290+/-62%,P<0.01) compared to the control group. In conclusion, antigen challenge induces an activation of ET-1 gene expression during the early response in Brown-Norway rats, suggesting a contribution of this protein to the development of bronchoconstriction.