saffari mr

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherogenesis. Antioxidants that can prevent LDL oxidation may act as antiatherogens. Our understanding of the mechanism of LDL oxidation and factors that determine its susceptibility to oxidation is still incomplete. Copper is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper. Therefore we investigated the effect of α-tocopherol (as a major fat soluble antioxidant) on copper bound to LDL and furthermore effect of this binding on the susceptibility of LDL to oxidative modification. In this study LDL was isolated from EDTA-plasma (1 mg EDTA/ml blood) by ultracentrifugation using a single-step discontinuous gradient. Then α-tocopherol was added to LDL and incubated for 1 h at 37° C. The oxidation rate of LDL was estimated by thiobarbitoric acid reactive substances (TBARS) after CuSO4 addition. Finally, the effect of α-tocopherol on formation of LDL-copper complex by gel filtration was studied. Our results showed that α-tocopherol (dose dependently) suppressed the formation of TBARS and LDL-copper complex. The α-tocopherol with concentrations of 10, 50 and 100 µM reduced susceptibility of LDL to oxidative modification approximately by 2, 13 and 21 percent, respectively. Furthermore, addition of α-tocopherol to the LDL and CuSO4 mixture containing before hand prevented the formation of LDL-copper complex, approximately by 30 percent.In conclusion we found that α-tocopherol with inhibition of copper binding to LDL may decrease the susceptibility of LDL oxidation to this ion and thus could play a role in prevention of atherosclerosis.

Nitric oxide (NO) is a molecule required for many physiological functions, produced from L-arginine by NO synthases (NOS). It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS (iNOS) in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially carcinogenic. Due to the short half-life of NO, usually its end products (nitrate or nitrite) are measured as an index of NO production. There is evidence that expression of iNOS in tumor cells, including acute myeloid leukemia and chronic lymphocytic leukemia increased. In this study, the levels of nitrate and nitrite (nitric oxide products) in the serum of patients with acute leukemia were determined.The serum levels of these compounds were measured in 40 acute leukemia patients. The results of serum nitrite and nitrate of patients were compared with corresponding values obtained in 40 healthy volunteers. These results indicate that patients with acute leukemia had a significant increase in the serum level of nitrite and nitrate.