SignificanceLiver steatosis, or fatty liver, is the most common liver disease in the world, affecting up to 25% of all Americans. There is currently no approved drug available for this condition, which may progress to serious disease, including steatohepatitis, fibrosis, and cirrhosis. Here, we show in rodent and human models of metabolic syndrome that steatosis can be prevented by a simple dietary approach. Inorganic nitrate, present in green leafy vegetables, is converted in vivo to nitric oxide (NO) in a process involving symbiotic host bacteria. NO then induces key metabolic regulatory pathways to ultimately reduce oxidative stress and improve cardiometabolic functions. Clinical trials would be helpful to tell if dietary nitrate is useful in treatment and prevention of fatty liver disease.

In this study, we demonstrated that plasma collected from women who subsequently developed preeclampsia caused increased heme oxygenase-1 (HO-1) production and decreased levels of nitric oxide (NO) markers in endothelial cells (HUVECs). Conversely, no changes in HO-1 or NO markers were found when HUVECs were treated with plasma from women who remained healthy throughout pregnancy. These alterations in HO-1 and NO markers were prevented by cotreatment with the polyphenol resveratrol, which also improved GSH levels. In addition, we evaluated changes induced by plasma incubation in the expression of genes and their related pathways associated with antioxidant defenses, such as Nrf2, ARE activity, and GSR. Collectively, our findings suggest that even before the appearance of clinical symptoms of preeclampsia, plasma from affected women is able to induce modifications in endothelial cells with respect to HO-1 production and NO markers. We believe that this in vitro strategy may offer an attractive alternative to the exploitation of candidate markers or screening molecules, such as resveratrol, for the prevention and management of preeclampsia.

Elevated levels of myeloperoxidase have been demonstrated in women with preeclampsia where it may contribute to endothelial dysfunction mediated, in part, by nitric oxide impairment. In this study, we investigated myeloperoxidase in hypertensive disorders of pregnancy and its contribution to the impairment of the vasodilator nitric oxide. We found higher levels of myeloperoxidase in supernatant from human umbilical vein endothelial cells cultures incubated with plasma from preeclampsia group compared with healthy pregnant women. Further, we measured plasma concentration and activity of myeloperoxidase in 219 healthy pregnant women, 130 gestational hypertension (on antihypertensive therapy or not), and 143 preeclampsia patients (on antihypertensive therapy or not). We found that patients with preeclampsia and gestational hypertension without antihypertensive treatment showed higher levels and activity of this enzyme, respectively. Moreover, the inhibition of myeloperoxidase activity in vitro improved nitric oxide bioavailability. Our results indicate a higher cardiovascular risk in pregnant women with hypertensive disorders, and that active myeloperoxidase may play a role in endothelial dysfunction in these conditions by impairment of nitric oxide availability. Besides, the use of antihypertensive drugs seems to decrease enzyme levels suggesting a new protective feature for these drugs.

Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (H2S) have been reported previously. However, no studies examined involvement of H2S in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished H2S plasmatic levels. In order to expand our findings, male Wistar rats were divided into four groups: Saline, Pb, NaHS, and Pb + NaHS. Pb-intoxicated animals received intraperitoneally (i.p.) 1st dose of 8 μg/100 g of Pb acetate and subsequent doses of 0.1 μg/100 g for seven days and sodium hydrosulfide- (NaHS-) treated animals received i.p. NaHS injections (50 μmol/kg/twice daily) for seven days. NaHS treatment blunted increases in systolic blood pressure, increased H2S plasmatic levels, and diminished whole-blood lead levels. Treatment with NaHS in Pb-induced hypertension seems to induce a protective role in rat aorta which is dependent on endothelium and seems to promote non-NO-mediated relaxation. Pb-intoxication increased oxidative stress in rats, while treatment with NaHS blunted increases in plasmatic MDA levels and increased antioxidant status of plasma. Therefore, H2S pathway may be involved in Pb-induced hypertension and treatment with NaHS exerts antihypertensive effect, promotes non-NO-mediated relaxation, and decreases oxidative stress in rats with Pb-induced hypertension.