Role of Copper in the Regulation and Accumulation of Superoxide Dismutase and Metallothionein in Rat Liver

Abstract

Weanling male Sprague-Dawley rats were fed one of four diets that varied in Cu, Zn or Cd content. To the control diet (I) Cu, Zn and Cd were added at 10, 100 and 0 mg/kg diet, respectively. Diets II and III also contained 10 mg/kg of dietary Cu, except that Zn was elevated to 1000 mg/kg for diet II, or Cd was added at 10 mg/kg for diet III. Diet IV was deficient in Cu (less than 1 mg/kg) with Zn at 100 mg/kg and no added Cd. At wk 6 postweaning, half of the rats fed diets I and IV were injected once with Cd acetate (5 mg Cd/kg body weight). The immediate response to Cd injection was an increase in metallothionein accumulation (three- to fourfold) and in Cu,Zn superoxide dismutase (SOD) accumulation (1.2- to 1.5-fold) in liver. SOD was estimated in an ELISA. These responses were not influenced by a change in Cu status (I vs. IV). However, in functional assays, SOD enzymatic activity was about half that of the control values. In this regard, SOD appears to be given high priority with respect to the utilization of cellular Cu, i.e., a 10-fold reduction in hepatic Cu only resulted in a twofold reduction in SOD activity and the amount of apoenzyme remained at normal levels.

Ethanol-induced changes in hepatic free radical defense mechanisms and fatty-acid composition in the miniature pig

“…In both studies, histopathological findings in the liver were minor and were limited to redistribution of SDH staining to the centrilobular hepatocytes, consistent with mitochondrial abnormalities. The finding of lower CuZnSOD and GPx activities in the ethanol-fed pigs than in controls is consistent with findings by other groups who demonstrated reductions in the activities of these enzymes as a result of ethanol ingestion in rat and primate models (10, 31) and as a result of copper deficiency in the rat (32,33).Despite reductions in several components of the antioxidant defense system, lipid peroxidation as assessed by production of TBARS was statistically lower in liver homogenate and mitochondrial and microsomal fractions from ethanol-fed pigs than in controls. When pigs were fed diets lower in fat for 11 mo, ethanol feeding resulted in lower homogenate and mitochondrial TBARs as well, but these differences were not statistically significant (7).…”

Copper Deficiency Suppresses Effector Activities of Differentiated U937 Cells

“…Alternatively, Cu,Zn-SOD may have high priority for intracellular Cu in phagocytic cells because they generate large quantities of reactive oxygen species (ROS) for killing microorganisms. Chung et al (1988) showed that the decline in Cu,Zn-SOD activity in the liver of Cu-deficient rats was much less than the reduction of Cu in this tissue. It is also interesting to note that Cu,Zn-SOD activity was 53% higher (P Ͻ 0.05) in differentiated U937 cells compared with that in replicating, nondifferentiated cultures of U937 (5.79 Ϯ 0.11 vs. 3.78 Ϯ 0.08 U/mg protein, respectively; n ϭ 6).…”

The role of oxidative stress in renal injury induced in rats by losartan exposure during lactation

“…Other studies also show increased SOD expression in conditions that led to oxidative damage, which was considered by the authors as a compensatory mechanism. [53][54][55] The expression of nitrotyrosine was increased in the renal cortex from losartan-treated animals. The peroxynitrite anion is produced by the reaction between the superoxide anion and nitric oxide, and protein tyrosine nitration is considered a consequence of peroxynitrite formation.…”