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Pharmacological particulars
Pharmacotherapeutic group: mineral supplements.
ATCvet code: QA12CX99.
Pharmacodynamic properties
Manganese is indispensable for the action of glycotransferase. This enzyme plays a role in the formation of the mucopolysaccharide chondroitin sulphate, which is a component of cartilage and due to its action on the formation of cartilage, it is also important for bone formation. Mn is an important component of Mn superoxide dismutase enzyme used in the enzymatic antioxidant system.
Although manganese is also part of pyruvic carboxylase and several other enzymes, other divalent cations may serve as alternatives for its role in the activity of these enzymes.
Copper forms an integral part of a number of metalloproteins notably caeruloplasmin, monoamine oxidase, lysyl oxidase, cytochrome C and superoxide dismutase enzymes. Zinc acts as a cofactor of numerous enzymes, e.g. alcohol dehydrogenase, carbonic anhydrase and carboxypeptidase. Zn is an important component of Zn superoxide dismutase enzyme used in the enzymatic antioxidant system. Zinc plays a role in protein synthesis and cell division. It also exerts crucial influence on the maintenance of cell membrane stability and in the function of the immune system. The connection between the known physiological functions of zinc and the various manifestations of zinc deficiency remain largely unexplained. Zinc interacts with several metabolic ions. Copper, calcium and phytate (a constituent of cereals) reduce zinc absorption; cadmium and zinc compete with each other.
Selenium exerts an antioxidative effect at the cell membrane against hydrogen peroxide and lipoperoxides. The effects are related to enzymatic activity of glutathione peroxidase (GSHPx) which contains selenocysteine. Selenium’s protective antioxidative action is partially linked to that of vitamin E. Selenocysteine is also an integral component of other functional proteins e.g. tetra- idothyronine-5-I-deiodinase (involved in metabolism of thyroid hormones) but the full extent of the biochemical mode of action of selenium in the body still remains to be elucidated.

Pharmacokinetic particulars
Absorption:
∙ Following subcutaneous administration, the trace minerals are rapidly absorbed from the injection site.
Distribution:
∙ Once absorbed, manganese is transported to organs rich in mitochondria (in particular the liver, pancreas, and pituitary) where it is rapidly concentrated. The main organ involved in manganese accumulation is the liver which accumulates significantly higher levels of manganese statistically than the kidney. The turnover of manganese in mammalian tissues is rapid.
∙ Absorbed copper binds to plasma albumin and amino acids in the portal blood and is transported to the liver where it is incorporated into caeruloplasmin and later released into the plasma. Hepatic copper is distributed in several subcellular fractions associated with copper-dependent enzymes and copper-dependent proteins. Copper is also found in erythrocytes in the form of erythrocuprein and other proteins and in bone marrow bound to metallothionein.
∙ Zinc accumulation is most striking in muscle, followed by the liver, kidney and blood. Zinc values in muscle, liver and kidneys are similar.
∙ Parenteral selenium is initially transported by serum albumin, after absorption, and later by alpha-2 and beta-1globulin fractions. Selenium is distributed throughout the body, but the highest amounts are present in the liver, kidneys, and muscle.
Metabolism:
∙ Manganese does not metabolize; it is absorbed and excreted unchanged.
∙ Copper is available for metabolism by the liver when present as the form bound to albumin. The liver is the major storage organ for copper where it is protein bound, followed by the kidney, muscle and blood.
∙ After absorption into the body, zinc becomes bound to protein complexes, the most important of which is metallothionein, which acts as a carrier and transport mechanism. As an element zinc is not metabolized per se. Zinc does not accumulate in the body following continued [excessive] exposure.
∙ The metabolic process involving selenium is dependent on the chemical form and dose as well as on nutritional status. Major metabolites are methylated selenites. Two major metabolic products of selenite have been identified: dimethyl selenide and a tri­­methyl­­selenonium ion.
Excretion:
∙ The liver, pancreas, adrenals and intestine play a role in the predominantly faecal excretion of manganese. Small amounts may be excreted in urine. For calves, 21% of an injected dose of manganese is excreted in bile.
∙ Excess copper is excreted mainly via bile and faeces, though urinary losses account for 0.5% to 3% of the daily intake.
∙ Excretion of absorbed zinc takes place mainly via bile (80%) and less so via urine and sweat.