[Effects of vitamin E supplementation on activity of serum paraoxonase, SOD, GPX enzymes and lipid profiles in beta major thalassemia patients]

In pathogenesis of beta major thalassemia, tissue damage is occurring due to oxidative stress. The present study was designed to evaluate the effects of vitamin E supplementation on serum Paraoxonase, SOD, GPX enzyme activity and lipid profiles in beta major thalassemia patients. In this clinical tiral study, Sixty [25 males, 35 females] beta major thalassemia patients with age >/= 18 years who had criterias to enter the study, were selected randomely in two groups. The patients in interventional group, vitamin E at a dose of 400 mg/day were given for three months, with no supplementations in control group. The enzyme activities of paraoxonase, SOD, GPX and lipid profiles [LDL-c, HDL-c, triglyceride, total Antixidant Capacity] were measured prior and after 3 months in both case and control groups. Data analyzed by using paired t-test. Significant increases in serum levels of vitamin E, Paraoxonase activity, HDL cholesterol [P<0.001], BMI [P

Paraoxonasa: sus múltiples funciones y regulación farmacológica / Paraoxonase: its multiple functions and pharmacological regulation

La homocisteína, aminoácido no-proteico, es un importante factor de riesgo de aterosclerosis y trombosis, afecta la vasodilatación y la función normal del endotelio vascular, es pro-inflamatoria e induce estrés de retículo endoplásmico. Su conformación más reactiva, la homocisteína tiolactona, producto de la acción no específica de la metionil-t RNA sintetasa, se incorpora a proteínas mediante puentes disulfuro (S-homocisteinilación) o uniones amida (N-homocisteinilación) produciendo graves efectos sobre la estructura y función proteica conduciendo a toxicidad celular, respuestas autoinmunes y aterogénesis. La enzima paraoxonasa-1, integrante de la lipoproteína de alta densidad, fue inicialmente considerada por su capacidad de hidrolizar derivados organofosfato, pero luego se le atribuyó un importante papel protector contra la aterosclerosis por prevenir la oxidación de lipoproteínas e hidrolizar homocisteína tiolactona. Existen evidencias acerca del papel de paraoxonasa-1 en la enfermedad vascular. Los factores genéticos (polimorfismos de la paraoxonasa-1), ambientales y el estilo de vida influyen sobre su concentración y actividad biológica, pero distintos fármacos como hipolipemiantes o cardioprotectores y otros, como antibióticos y esteroides, son también importantes moduladores. En la presente revisión se actualiza la más destacada información sobre los estudios clínicos y experimentales que permiten entender el papel que cumple esta enzima en la protección ante el desarrollo de la aterosclerosis.

Homocysteine, a non-protein amino acid, important risk factor for atherosclerosis and thrombosis, causes dysfunction of vascular endothelial cells traduced in inadequate vasodilatation mechanism, is pro-inflammatory and induces endoplasmic reticulum stress. The more reactive conformation is the homocysteine thiolactone (HcyT), product to the nonspecific action of methionyl-tRNA synthetase, which is incorporated into proteins by disulfide bonds (S-homocysteinilation) or amide bonds (N-homocysteinilation) affecting protein structure and function leading to cell toxicity, autoimmune responses and atherogenesis. The enzyme paraoxonase-1 (PON1), part of high density lipoprotein (HDL), had been studied only for its ability to hydrolyze organophosphate derivatives. But, more recently it has been attributed other important role. The enzyme activities are involving in protecting against the development of atherosclerosis, by preventing oxidation of lipoproteins and hydrolyze HcyT. There is growing evidence about the protective role of PON1 in vascular disease. Genetic factors (polymorphisms of the PON1), environmental and lifestyle influence their concentration and biological activity, but drugs used as cardioprotectives and lipid-lowering or others, such as antibiotics and steroids, are also important modulators. This review is an updated of the most prominent information on clinical and experimental studies for understanding the role of the PON-1 in the protection against development of atherosclerosis.