Environmental xenobiotics

A xenobiotic is a compound which is foreign to a particular organism. The term ‘xenobiotic’ is a combination of the Greek words ‘xenos’ meaning strange or foreign and ‘bios’ meaning life. They are mostly synthetic substances used as agrochemicals, pharmaceuticals, petrochemicals, colorants, adhesives, preservatives and certain chemicals in plastics.

 Kinds

The xenobiotics may be naturally occurring as well as man-made (anthropogenic). The man-made chemicals are synthetic substances like pesticides, organic solvents, medicaments, ethanol etc. The naturally occurring chemicals are produced by plants , microorganisms or animals as ‘chemical warfare agents’. E.g. pyrethrins, nicotine, mycotoxins, tetrodotoxin (newt) and antibiotics.

    Xenobiotics can be exogenous to living organisms, which include drugs, food additives, pollutants, insecticides, chemical carcinogens etc. They are not normally ingested or utilized by the organisms.

Endogenous xenobiotics are not foreign substances but are synthesized in the body or produced as metabolites of various processes in the body e.g. bilirubin, bile acids, steroids, eicosanoids and certain fatty acids.

Sources

 The major sources of xenobiotic compounds are from the chemical and pharmaceutical industries, mining operations, fossil fuels and intensive agriculture.  Food additives are xenobiotics which have no nutritional value, are of no use in the body and can be harmful, if consumed in excessive amounts. Human beings are increasingly exposed to the kinds and amounts of xenobiotic agents from industrial, agricultural, pharmacological and lifestyle applications.

Sites of action

 The xenobiotic agents target the active sites of enzymes, DNA (genetic material) and lipid membranes.

Mechanism of toxicity

The exposure to xenobiotic agents disrupts normal cell functions. They easily bind and damage structural and dynamic proteins e.g. enzymes. They also bind and damage DNA and induce mutations (nucleophilic).  They bind and damage lipid membranes (lipophilic).

They react in the cell with oxygen to form ‘free radicals ‘which damage lipid, protein and DNA.

Effects of xenobiotics

The metabolism of xenobiotics can result in cell injury/cell death by cytotoxicity, immunologic damage (altering its antigenicity) or cancer (disorder in cell growth).

The xenobiotics may directly bind to a cellular component and inhibit its normal function. For example carbon monoxide binds to haemoglobin in the red blood cells and prevents the haemoglobin from binding with oxygen.

Cadmium binds with a transporting blood protein metallothionein which accumulates in the kidney and damage the filtering function (tubular cells).

Metabolism of xenobiotics

The main organ involved in xenobiotic metabolism is liver. The xenobiotic transforming enzymes are present in the cytosol and endoplasmic reticulum of hepatocytes.

The biotransformation involves phase I and phase II reactions.

The main purpose of the reactions is converting the xenobiotic lipophilic (lipid-soluble) agents into hydrophilic compounds and facilitates excretion. First phase of reactions are performed by liver or gut enzymes before the compounds reaches the systemic circulation and limits its bioavailability. Several enzyme systems participate in phase one metabolism of xenobiotics. The cytochrome P450s (CYPs:450s) detoxify and / or bioactivate a vast number of xenobiotic chemicals. Phase I involves the addition of reactive functional groups by oxidation, reduction or hydrolysis.  Phase I reactions convert xenobiotics into more reactive metabolites (metabolic activation). Phase II biotransformation is catalysed often by the ‘transferase’ enzymes that perform conjugating reactions. Phase II reactions include glucuronidation, sulfation, methylation, acetylation, glutathione conjugation and amino acid conjugation.  Phase II reactions cause the xenobiotic metabolites into more hydrophilic and readily excretable compounds.

‘Poisons are xenobiotics, but not all xenobiotics are poisonous’