Higher Serum Iron Is Associated With Increased Oxidant Stress in HIV-Infected Men

Abstract

Background F2-isoprostanes (F2-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women than men. We explored whether the effect of hemoglobin (Hgb), serum iron, or anemia on F2-IsoP is different between HIV-infected women and men. Methods Plasma F2-IsoP were quantified by gas chromatography/mass spectrometry; clinical and laboratory data were collected at enrollment or from the medical record. Multivariable linear regression was used to assess associations between F2-IsoP and Hgb, anemia as a dichotomous variable, and serum iron with adjustment for age, sex, race, body-mass index, CD4+ lymphocyte count, self-reported current smoking status, and antiretroviral therapy. Results Compared to men, women had lower Hgb (median [IQR] 12.7 [11.8-13.9] vs. 14.9 [13.7-15.8] g/dL, P<0.001), lower iron levels (75 [47-97] vs. 90 [69-121] μg/dL, P=0.004), more anemia (29% vs. 10%, P<0.001), and higher levels of F2-IsoP (42 [32-62] vs. 36 [25-46] pg/mL, P<0.001). The relationship between iron and F2-IsoP differed significantly between men and women (interaction P=0.02). Men had a 21% (95% CI: 8%-36%) increase in F2-IsoP per interquartile increase in iron (P=0.001); while no relationship was seen among women (-4% [-17%-13%], P=0.65). Conclusions Although women have overall higher F2-IsoP than men, a relationship between circulating F2-IsoP and iron levels was observed in men but not in women with HIV infection. The association between female sex and higher F2-IsoP is not explained by iron or Hgb levels as the association persists when controlling for these factors. The role of iron in oxidant stress and sex-specific differences among HIV-infected individuals require further study.

The isoprostanes—25 years later

“…Multiple studies have clearly shown that levels of F 2 -IsoPs, as measured in the plasma or urine, increase in obese adults [74,96–101]. F 2 -IsoPs have been positively correlated with body mass index (BMI), waist circumference (WC), visceral fat area, and percent body fat [102–118]. Interestingly, recent epidemiological studies have implicated possible racial differences in the association of F 2 -IsoPs with obesity.…”

Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

“…In particular, high serum iron levels are associated with increased oxidative stress in HIV-infected men. 1 As a result, the levels of cellular iron are tightly regulated. The role of iron in bacterial and fungal infections is well established [2][3][4] ; however, changes in cellular or systemic iron after HIV infection is not well understood.…”

Antiretroviral Therapy Initiation Alters the Redox System of Asymptomatic HIV‐Infected Individuals: A Longitudinal Study

“…Hulgan et al [6] also found elevated plasma concentrations of F2-isoprostane in PLWHA under cART and viral suppression. Crist et al [31] showed higher 8-isoprostane levels in HIV-infected women as compared to men; therefore it is worth mentioning that, in our study, the analysis was adjusted for gender, age, and other variables that could be confounding.…”