ubiquinol and Iron-Overload

This study describes the in vivo response of rat testes to acute iron overload. Male Wistar rats (250-300 g) were injected ip with iron dextran at doses of 250 (Fe250), 500 (Fe500), or 1000 mg/kg body wt (Fe1000) or with saline (C). Parameters of oxidative stress and iron toxicity were measured 20 h after injection. Total iron content was 3.5-, 5.3-, and 10.4-fold higher in the Fe250, Fe500, and Fe1000 groups, respectively, compared to controls (320 +/- 22 nmol/g tissue). Histological studies showed that: (a) iron accumulated in the sperm and other testes cells, and (b) spermatogenesis was markedly lower in the Fe1000 group. The concentration of alpha-tocopherol, ubiquinol-9, and ubiquinol-10 in the testes was inversely correlated with the extent of oxidation. Testes chemiluminescence was 45% higher in the Fe1000 group compared to controls (41 cps/cm(2)). Endogenous levels of lipid oxidation, evaluated as 2-thiobarbituric acid-reactive substances, were 46, 73, and 82% higher in the groups Fe250, Fe500, and Fe1000, respectively, than in controls (33.6 +/- 1.4 nmol/g tissue). Oxidative damage to DNA evaluated by the presence of 8-oxo-2'-deoxyguanosine (oxo(8)dG), was 26, 39, and 74% higher in the Fe250, Fe500, and Fe1000 groups, respectively, than in the C group (2.3 +/- 0.1 oxo(8)dG/10(5)dG). Protein oxidation was measured as protein thiols and carbonyl content in proteins and glutamine synthase activity. Protein thiols content and glutamine synthase activity were similar in all the groups, while the protein-associated carbonyls content was 96% higher in the Fe1000 group than in the C group (2.1 +/- 0.4 nmol/mg protein). No changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were observed. The results showed that in vivo iron overload induced oxidative stress and the impairment of spermatogenesis in rat testes that were dependent on the amount of iron supplemented and its accumulation in the tissue.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Deoxyguanosine; DNA; Iron; Iron Overload; Lipid Peroxidation; Luminescent Measurements; Male; Oxidative Stress; Proteins; Rats; Rats, Wistar; Testis; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E

The effect of dietary alpha-tocopherol (alpha-T) supplementation on iron overload-dependent oxidative damage was studied. Male Wistar rats were fed diets supplemented with 2.5% carbonyl iron and/or 200 mg/kg of alpha-tocopheryl acetate for 6 weeks. Oxidation of lipids and proteins were increased by iron overload in rat liver, and alpha-T dietary supplementation effectively prevented these effects. Iron overload decreased both, catalase and Mn-superoxide dismutase activities by 49 and 54%, respectively, with no effect on glutathione peroxidase activity. Alpha-T supplementation did not prevent the inhibition measured in catalase and Mn-superoxide dismutase activities. Iron dietary excess had no effect on liver alpha-T and ubiquinol 9 (UQ9) content. Ubiquinol 10 (UQ10) content after iron overload was decreased by 58 and 54% in whole liver and liver mitochondria, respectively. Alpha-T supplementation led to significant increases in alpha-T, UQ9 and UQ10 content in liver, as compared to control values, and partially prevented the decrease in UQ10 content due to iron excess. The results presented here indicate that initial stages of iron overload led to oxidative damage in liver (evaluated in terms of lipid and protein oxidation) with a decline in antioxidant defenses. alpha-T supplementation affected the liver content of lipid soluble antioxidants, suggesting a concerted antioxidant response at the cellular level to modulate the effect of excess iron availability.

Topics: Animals; Antioxidants; Catalase; Iron Overload; Lipid Peroxidation; Male; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone; Vitamin E