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. 2019 Jun 19:2019:1629638.
doi: 10.1155/2019/1629638. eCollection 2019.

Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

Matthew A Tucker  1 , Brandon M Fox  1   2 , Nichole Seigler  1 , Paula Rodriguez-Miguelez  1 , Jacob Looney  1 , Jeffrey Thomas  1 , Kathleen T McKie  3 , Caralee Forseen  4 , Gareth W Davison  5 , Ryan A Harris  1   5
Affiliations

Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

Matthew A Tucker et al. Oxid Med Cell Longev. .

Abstract

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3%), compared to no change following placebo (Δ - 0.8 ± 1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 μM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 μM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

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Figures

Figure 1
Figure 1
Schematic illustrating the recruitment/enrollment process and overall experimental design. Flow-mediated dilation (FMD) was assessed in healthy controls (n = 18) and in patients with CF (n = 18) following an antioxidant cocktail (AOC). In a subgroup of patients with CF (n = 9), measures of oxidative stress balance were assessed following ingestion of the AOC and a placebo condition.
Figure 2
Figure 2
Changes in flow-mediated dilation (FMD) in patients with CF following either the AOC treatment (CF-AOC; n = 18) or the placebo (CF-PLC; n = 9). ∗Significantly greater than CF-PLC (p = 0.032). Values are presented as the mean ± SEM.
Figure 3
Figure 3
Changes in plasma levels of antioxidants (a, b) and lipid hydroperoxide (LOOH, (c)) in patients with CF in the AOC treatment and placebo (PLC) condition (n = 9). ∗Significant difference between treatments when controlling for HbA1c as an index of disease severity (p < 0.05).
See this image and copyright information in PMC

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