Effect of copper intoxication on rat liver proteasome activity: Relationship with oxidative stress

Abstract

Copper toxicity is associated with formation of reactive oxygen species, which are capable to oxidize proteins. The selective removal of the latter by the 20S proteasome is considered an essential part of the cell antioxidant defense system. The aim of the present study was to investigate whether peptidase activities of rat liver proteasomes were affected by chronic (40 mg CuSO(4)/rat/daily with the drinking water for 2 weeks) and acute (20 mg/kg CuSO(4), s.c.) copper treatment. To evaluate the role of proteasome, its inhibitor MG132 was also used. The degree of copper-induced oxidative stress (OS), established by measuring lipid peroxidation, protein oxidation, and cellular glutathione level, as well as activities of antioxidant enzymes--catalase, superoxide dismutase, and gultathionine peroxidase, depended on the mode of copper administration. Chronic copper administration (mild oxidative stress) did not affect proteasome activities, whereas acute copper treatment (severe oxidative stress) caused a decline in chymotryptic- and tryptic-like activities. The treatment of copper-loaded animals with MG132 did not change copper-induced alterations in the tested indices, except an additional increase in protein oxidation and inhibition of glutathionine peroxidase activity. The results suggested that the in vivo copper-induced oxidative stress was associated with changes in the catalytic activity of proteasome.

Chronic copper exposure elicit neurotoxic responses in rat brain: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and neurobehavioral parameters

“…It was attributed to ROS production particularly involvements of hydrogen peroxide in the lipid per oxidation. Our results are also in agreement with an earlier study (54) suggesting that copper significantly increased lipid per oxidation levels in the hepatocytes through ROS generation which may lead to significant elevation in TBARS levels. Concurrently, copper overloads significantly decrease the Superoxide dismutase activity in both copper sulphate treated groups in the brain tissue.…”

Advances in the mechanism of high copper diets in restraining pigs growth

“…Secondly, when the liver is damaged, it may cause imbalances in blood glucose homeostasis such as glycogen synthesis, gluconeogenesis and transformation, while excessive blood glucose concentration stimulates the CNS, causing abnormal release of GH, ghrelin and NPY, hence inhibiting feeding and growth of pigs (Kmiec, 2001;Pocai, Obici, Schwartz, & Rossetti, 2005). Thirdly, after the oxidative damage of liver cells (Ozcelik, Ozaras, Gurel, Uzun, & Aydin, 2003), the liver's ability to scavenge bacteria, viruses, antigens and denatured proteins in the blood is weakened, therefore making pigs more susceptible to diseases (Alexandrova et al, 2008). Hence, long-term consumption of high copper diets may weaken liver function and inhibit the growth rate of pigs (Figure 3).…”

Histochemistry evaluation of the oxidative stress and the antioxidant status in Cu-supplemented cattle

“…Studies in the liver of rats reported increased oxidative stress damage of proteins and protein degeneration caused by Cu (Alexandrova et al, 2008), lipid peroxidation expressed as MDA activity or immunoreactivity (Zhang et al, 2000;Ozcelik and Uzun, 2009) and DNA damage (Gaetke and Chow, 2003;Alexandrova et al, 2007) that finally could lead to apoptotic cell death (Rana, 2008). Lipid peroxidation produced by ROS is considered to be the most likely mechanism to damage proteins, rather than a direct action of ROS generated by Cu or other metals overload (Yamada et al, 1992;Ogihara et al, 1995).…”

“…It is widely accepted that diagnosis of chronic Cu toxicity is complicated and that health risk assessment cannot be based solely on Cu chemical analyses (Walker, 1998;Kakkar and Jaffery, 2005). However, little attention was paid to the liver tissue from a histological point of view and when it does, the studies focused in rat tissue or ruminants that were experimentally induced clinical Cu intoxication (Gooneratne et al, 1979;Kumaratilake and Howell, 1987;Alexandrova et al, 2008).…”

“…It is widely accepted that diagnosis of chronic Cu toxicity is complicated and that health risk assessment cannot be based solely on Cu chemical analyses (Walker, 1998;Kakkar and Jaffery, 2005). However, little attention was paid to the liver tissue from a histological point of view and when it does, the studies focused in rat tissue or ruminants that were experimentally induced clinical Cu intoxication (Gooneratne et al, 1979;Kumaratilake and Howell, 1987;Alexandrova et al, 2008).In a recent study carried out by our research group, it was found that the addition of 15 mg/kg Cu to a standard concentrate feed, the commonly used Cu supplementation in cattle intensive production systems in NW Spain and also in many European countries, was not justified to maintain an adequate Cu status in the animals or to improve productive parameters. On the contrary, a high percentage of animals which had been fed this Cu-supplemented diet had hepatic Cu concentrations that could be associated to subclinical Cu toxicity (García-Vaquero et al, 2011).…”