Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

Abstract

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

“…However, under certain conditions it can be harmful, especially for the brain. Although the cellular metabolism of the CNS requires iron as a redox metal for energy generation, mainly the production of ATP, nervous tissue is vulnerable to oxidative damage generated by excess iron and decreased antioxidant systems [ 110 , 111 , 112 , 113 ]. The explicit identification of ferroptosis in vivo is hampered by the lack of specific biomarkers, due to several factors that may be associated with the ferroptotic process.…”

Effects of fullerenol nanoparticles on kidney tissue in sevoflurane‑treated rats

“…Therefore, in this study, PON-1 levels in the renal tissues were used to determine the protective effects of fullerenol. PON-1 plays a signifi cant role in delaying/ inhibiting the oxidation and in preventing the accumulation of lipid peroxides (40). The results of this study suggested that antioxidant activity of PON-1 was an important factor which provided protection from oxidative stress and lipid peroxidation against sevofl urane-related renal injury.…”

Paraoxonase Role in Human Neurodegenerative Diseases

“…The PON1 arylesterase and lactonase activities contribute to the maintenance the physiological functions of HDL in both cells and tissues. Changes in PON1 activities and HDL function have been associated with physiological conditions such as pregnancy and aging, as well as pathophysiological conditions such as atherosclerosis, diabetes, cerebrovascular and neurodegenerative diseases, iron overload, renal disease, drug metabolism and detoxification of organophosphate compounds [ 25 , 40 , 41 , 42 , 43 ]. Diet rich in fruits and vegetables, olive oils, polyphenols and flavonoids such as quercetin, increases the activity of the enzyme PON1, contributing to the reduction of oxidative stress in the degeneration process [ 44 , 45 , 46 , 47 , 48 , 49 ].…”

“…In addition, serum ferritin concentration was inversely correlated with PON1 activity [ 255 ]. The association between ferritin and PON1 may be a link between inflammation and the enzymatic antioxidant system [ 43 ]. Decreased serum paraoxonase activity in PD patients has been associated with increased oxidative stress, lipid peroxidation and changes in iron metabolism markers [ 256 , 257 , 258 ].…”