Pharmacology Metabolism
XENOBIOTIC METABOLISM IN ANIMALS
XENOBIOTIC METABOLISM IN ANIMALS
A compound foreign to a given organism is known as xenobiotic, e.g. Medicinal drugs, agricultural chemicals, industrial chemicals and environmental contaminants. Drugs such as antibiotics are not produced itself in human body nor they are part of normal diet. Xenobiotics present a number of hazards to man and environment such as toxicity, carcinogenicity and bioaccumulation. Many xenobiotics are recalcitrant and persist in the environment. Xenobiotics are becoming a large increasingly problem in sewage treatment system. Recalcitrant xenobiotic compounds are halocarbons (chloroform, DDT, BHC, lindane, freons and dalapon etc.), polychlorinated biphenyles (PCB’s), synthetic polymers (polyethylene, polystyrene and polyvinylchloride), alkyl benzyl sulphonates and oil mixtures. Many hydrocarbons are cause of biomagnification. The disruption of the reproductive system of male and female animals in the wild has been attributed to environmental chemicals, e.g. DDT. Many compounds in the environment are capable of acting as endocrine disruptors, e.g. chlordane, trans-nonachlor and PCB.
When xenobiotics enter in the body they take part in the metabolism, they become deactivated by oxidation, reduction, hydrolysis, hydration and conjugation and finally secreted by different routes such as urine, feces, breath and sweat. The enzymes that take part n metabolism of xenobiotics are very important for the pharmaceutical industry. Liver plays central role in modifying ingested substances because it is the only organ situated between the intestine and systemic circulation.
William, R.T. in his book “Detoxification mechanism- The metabolism and detoxication of drugs” described two phase metabolism of xenobiotic compounds.Phase I includes oxidation, reductions and hydrolysis and phase II comprised of conjugation reactions. According to him phase II reactions are actually detoxication reactions.
Oxidation
Body has ability to oxidize cinnamic acid, benzene, toluene and o-xylene in hippuric acid, phenol, benzoic acid and o-toluic acid.
Reduction
Body has ability to reduce nitro groups to the corresponding amines. 1939 Noble prize winner G. Domagk studied reduction of protonsil to sulphanilamide, helpful in treptococcal infection treatment.
Hydroxylation
Cytochrome P450 is useful to scientists of major fields such as molecular biology, pharmacology, biochemistry and medicines. This class of oxygenases had requirements for both as oxidant (molecular oxygen) and reductant (NADPH) which is called as ‘mixed function oxidases’.
Sulfate conjugation
Oxidation product of benzene, phenol conjugates with sulfate to form phenyl sulfate. Baumann was able to isolate and characterize phenol sulfate from the urine of a patient who had been treated with phenol as an antiseptic. He also studied conjugation in catechol, bromobenzene, indole and aniline.
Glucuronidation
First sugar conjugate euxanthic acid (Indian yellow) was isolated from the urine of cows fed with mango leaves. Hydroxy-camphpor glucuronide was isolated after dose of camphor from the urine of dogs.
Finally transporters recognize them and pumped out of cells which are excreted out of animal body.
About the Author
SWAPANIL YADAV
Drug Metabolism
Metabolism Masterclass