Handbook of Vitamin C Research

Protective Effect of Vitamin C 337exposed rats, a protective effect of thymoquinone treatment was observed in the rat kidney[53].In humans, the majority of studies have shown beneficial effects on vitamin C treatmentafter lead intoxication. In a long cross-sectional study followed in 19578 individuals, Simonand Hudes [54] analyzed the association between serum vitamin C concentrations and theprevalence of elevated blood lead levels. This study showed an inverse relationship betweenserum vitamin C levels and blood lead concentrations. However, there were no correlationsbetween vitamin C intake and blood lead concentrations [54]. Another study developed inAfrican American women, vitamin C supplementation significatively reduced blood leadlevels, showing a negative correlation between vitamin C and lead serum levels [55].Dawnson and Harries observed that after lead-contained drink intake, vitamin C treatmentproduced a reduction in lead retention [56].Several in vitro and in vivo studies have been realized to determine the beneficial effectsof vitamin C treatment on the deleterious effects of lead on the cardiovascular system. Whileanimal studies have shown that vitamin C treatment has beneficial effects against leadexposure, studies in humans have not shown similar evidence. Lead-induced hypertension isthe issue that has received more attention regarding the deleterious effect of lead in thecardiovascular system. Evidence of the participation of oxidative stress in the pathogenesis oflead-induced hypertension comes from an experiment that demonstrated normalization ofarterial pressure with infusion of the superoxide scavenger drug tempol in lead-exposed rats[39]. A number of other investigators have demonstrated the critical role of oxidative stress inthe pathogenesis of lead-induced endothelial dysfunction and hypertension in experimentalanimals. In this regard, Vaziri et al. observed that lazaroid, a non-chelating antioxidant,improved nitric oxide availability and reduced blood pressure in lead-exposed rats [57].Taken together, these findings suggest that lead reduced the availability of endotheliumdependentnitric oxide in the vascular wall. It was further supported by the fact that tempol, asuperoxide scavenger drug, normalized arterial pressure in lead-exposed rats [39]. Marques etal. demonstrated that concomitant administration of lead and vitamin C prevented an increasein mean arterial blood pressure, improved relaxation to both acetylcholine and sodiumnitroprusside and restored the normal protein expression of endothelial nitric oxide synthaseand soluble guanylate cyclase in the vascular wall [45]. Courtois et al. showed that vitamin Cpartially restored the expression of soluble guanilate ciclase in lead-induced isolated rat aorticsegments [58]. Moreover, vitamin C prevented lead-induced cyclooxygenase-2 expression inthe isolated rat aortic segments that was not observed with rofecoxib, an inhibitor ofcyclooxygenase-2 activity that failed to modify superoxide anion production induced by leadexposure of the vascular wall. It suggests that a superoxide anion was involved in theupregulation of cyclooxigenase-2 expression elicited by lead [58].Taken together, the above-described studies provide evidence that lead exposure causesoxidative stress and alterations of the nitric oxide pathway which culminate in developmentof arterial hypertension. The treatment of oxidative stress is traditionally equated with theadministration of antioxidants like vitamin C. However, perhaps the identification of thesource and control of the production of reactive oxygen species should be more useful.