Defective antioxidant defense system in patients with a human leptin gene mutation

Antioxidant defense system prevents the organism from the detrimental effec ts of free radicals via scavenging or inhibiting their formation. Changes i n the antioxidant defense mechanisms and alterations of several essential t race elements in both plasma and various tissues of ob/ob mice have been re ported previously. Recent finding of the restoration of the defective antio xidant enzyme activity after leptin treatment in ob/ob mice suggests a puta tive role of leptin in modulation of antioxidant enzyme activity. Therefore , the aim of this study was to investigate whether antioxidant enzymes and trace elements could also be altered in patients with leptin gene mutation. Seven patients (five men and two women, two of them are homozygous and 5 a re heterozygous) with leptin gene mutation and 31 healthy, sex- and age-mat ched and non-related to the patients (24 male and 9 female), control Volunt eers were enrolled in the study. Plasma and erythrocyte glutathione peroxid ase (GSH-Px) and erythrocyte copper-zinc superoxide dismutase (CuZn-SOD) ac tivities were measured spectrophotometrically. Plasma selenium (Se), mangan ese (Mn), zinc (Zn), copper (Cu), and iron (Fe) levels were measured by ato mic absorption spectrophotometry. Mean Cu and Fe levels in patients were no t significantly different than those in controls whereas mean Se, Zn0 and M n levels were significantly lower in patients than those of controls (P = 0 .007, P = 0.001, and P = 0.001, respectively). Erythrocyte GSH-Px (39%), pl asma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were significan tly lower than those of the control group (P = 0.001, P = 0.002, P = 0.001, respectively). In conclusion, our results demonstrate that the activity of antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreas ed in both homozygous and heterozygous subjects with leptin gene mutation. We suggest that both leptin and trace elements might be involved in the mod ulation of antioxidant defense system.