Oxidative stress in homocystinuria : findings in patients and in animal models

Abstract

Homocystinuria is an inborn error of amino acid metabolism caused by deficiency of cystathionine ß-synthase (CBS) activity, leading to the accumulation of homocysteine (Hcy) and methionine (Met) in biological fluids and high urinary excretion of homocystine (Hci). This accumulation leads to a variety of clinical manifestations, in different organs and tissues, as thinning and lengthening of the long bones, osteoporosis, dislocation of the ocular lens, thromboembolism and mental retardation, but the pathophysiology of this disease is not completely understood. In this context, this review addresses some findings obtained from patients and animal studies indicating that oxidative stress plays an important role in the pathophysiology of homocystinuria. Several studies have shown that enzymatic and non-enzymatic antioxidant defenses are decreased, as well as markers of lipid, protein, and DNA oxidative damage have been reported increased in blood, brain, liver and muscle in the animal models studied, as well as in homocystinuric patients, which may be due to an increased free radical generation or secondary to the deprivation of micronutrients which are essential for these defenses. A considerable set of data from in vitro and in vivo animal studies have shown that Hcy induces reactive species formation in brain rodent. Considering these findings, it is well established that oxidative stress may contribute to the damage found in homocystinuric patients. This review offers new perspectives for the treatment in homocystinuria, which may include the use of appropriate antioxidants as a novel adjuvant therapy for the patients.