RESUMEN
Paraoxonase 1 (PON1) is a cardioprotective enzyme associated with high-density lipoprotein (HDL). We tested the hypothesis that vitamin C protects HDL and PON1 from deleterious effects of hypochlorous acid, a proinflammatory oxidant. In our experiments, HDL (from human plasma) or diluted human plasma was incubated with hypochlorite in either the absence (control) or presence of vitamin C before measuring chemical modification and PON1 activities. Vitamin C minimized chemical modification of HDL, as assessed by lysine modification and accumulation of chloramines. In the absence of vitamin C, chloramines accumulated to 114 +/- 4 micromol/L in HDL incubated with a 200-fold molar excess of hypochlorite; but addition of vitamin C (200 micromol/L) limited formation to 36 +/- 6 micromol/L (P < .001). In plasma exposed to hypochlorite, IC(50) values of 1.2 +/- 0.1, 9.5 +/- 1.0, and 5.0 +/- 0.6 mmol/L were determined for PON1's phosphotriesterase, arylesterase, and (physiologic) lactonase activities, respectively. Vitamin C lessened this inhibitory effect of hypochlorite on PON1 activities. In plasma supplemented with vitamin C (400 micromol/L), PON1 phosphotriesterase activity was 72% +/- 17% of normal after incubation with hypochlorite (2 mmol/L), compared with 42% +/- 6% for unsupplemented plasma (P < .05). Similar effects were seen for other PON1 activities. In some experiments, vitamin C also appeared to reverse hypochlorite-mediated loss of PON1 phosphotriesterase activity; but this effect was not observed for the other PON1 activities. In conclusion, vitamin C attenuated hypochlorite-mediated loss of PON1 activity in vitro and may, therefore, preserve cardioprotective properties of HDL during inflammation.
Asunto(s)
Antioxidantes/farmacología , Arildialquilfosfatasa/sangre , Ácido Ascórbico/farmacología , Ácido Hipocloroso/farmacología , Lipoproteínas HDL/metabolismo , Ácido Ascórbico/sangre , Hidrolasas de Éster Carboxílico/sangre , Hidrolasas de Éster Carboxílico/metabolismo , Enfermedades Cardiovasculares/prevención & control , Humanos , Lipoproteínas LDL/metabolismo , Hidrolasas de Triéster Fosfórico/sangreRESUMEN
Adequate periconceptional consumption of folic acid can prevent neural tube birth defects, and all women capable of becoming pregnant are recommended to consume 400 microg/d. Most women, however, are unaware of this recommendation and do not consume adequate amounts of folic acid. It is important, therefore, that healthcare professionals, such as pharmacists, be capable of educating women regarding folic acid. The aim of this study was to assess knowledge regarding prevention of birth defects by folic acid among student (future) pharmacists in the final year of a professional degree program. Over a 3-y period (1998-2000), students (n = 98) enrolled in a PharmD program completed a survey consisting of five multiple-choice questions concerning folic acid and birth defects. Almost all students (93.9%) correctly identified folic acid as preventing birth defects. Of these students, many also knew that supplementation should begin before pregnancy (73.9%). Fewer, however, were able to correctly identify either the recommended level of intake (55.4%) or good sources of folic acid (57.6-65.2%). These results show that although student (future) pharmacists are aware of folic acid's ability to prevent birth defects, many lack the specific knowledge needed to effectively counsel women in future clinical practice.