Evaluation of chronic hepatic copper accumulation in cattle

Abstract:

Traditionally cattle were thought to be relatively tolerant of copper (Cu) accumulation, and cattle diets were regularly supplemented with Cu well above physiological needs. In recent years, however, an increasing number of episodes of Cu toxicity have been reported in cattle, in most cases associated with excessive Cu intake in the ration. It has also been reported that dietary supplements leading to Cu accumulation in the liver at concentrations only slightly above normal show negative effects on animal performance, in terms of reduced feed intake and average daily gain (subclinical toxicity). Identification of animals in the silent chronic phase of Cu accumulation is very important to avoid not only economic losses due to subsequent severe disease or death, but also to avoid subclinical disease. Currently available laboratory markers of Cu toxicity are mainly used for diagnostic purposes, i.e. to demonstrate changes associated with clinical manifestations already present. However, there is a clear need to identify markers of early changes, with a capacity to pbkp_redict risk of Cu accumulation in the liver before actual tissue or functional damage occurs. In this chapter, we evaluate the suitability of some blood parameters as potential markers of hepatic Cu accumulation in cattle during the silent phase as well as the use of in vivo biopsies for evaluation of risk of chronic Cu toxicity. Our results indicate that under moderately high Cu exposure, none of the blood markers currently available accurately pbkp_redicted hepatic Cu accumulation in cattle and analysis of Cu content in the liver is probably the best diagnostic tool available for assessing the risk of chronic Cu toxicity. However, the limit between safe-adequate Cu concentrations and those associated with toxicity is very narrow, and for this reason the total hepatic Cu concentration is not per se a good indicator of risk of toxicity in animals with marginal hepatic Cu concentrations. Studies of subcellular hepatic Cu accumulation indicate that the large-granule (lysosomal) fraction has a limited capacity for Cu sequestration and Cu content in this compartment tends to reach a plateau phase at relatively low Cu exposure levels, leading to higher Cu accumulation in the nucleus and cytosol. This pattern of Cu accumulation, as in sheep, may be due to the limited capacity for metallothionein binding of Cu and excretion in bile. Further research into the molecular basis of Cu homeostasis in cattle is essential to better understand the pathogenesis of chronic Cu hepatic accumulation and to validate the use of subcellular Cu parameters as potential markers of the risk of Cu toxicity in cattle.

Año de publicación:

2008

Keywords:

Fuente:

scopus