The environment that surrounds us consists of numerous chemical substances which, in one way or the other, come in contact with us. Many a times these compounds are a potent threat to our health. When these foreign entities enter our body, they interrupt with normal physiological activities of the cells and organs, creating a ruckus inside us, ultimately, leaving behind some grave consequences for us to bear. These uncalled guests of our body are together known as Xenobiotics.
Xenobiotics are omnipresent and pervasive. They may be present in the food or fresh water (mycotoxins, flavonoids, nitrates, nitrites, nitrosamines, PCBs, PAHs, arsenic, cadmium, chlorination of water), in air that we breathe in (organic metals, particulate matter of automobile smoke, cigarette smoke) and in the household (construction material that contains formaldehyde, styrene, acrylates, vinyl chlorides, pesticides, some cosmetic products).
To define, xenobiotics are substances that are pharmacologically, endocrinologically and toxicologically active, not produced endogenously and are thus, foreign to an organism. The term has been derived from a Greek word xenos that means foreigner or a stranger and bios that means life. It was coined by Mason, et al.
Majorly exogenous in nature, these compounds like food additives, chemical entities, insecticides, pollutants, carcinogens, enter the living body via edible food stuffs, drugs or inhaled from the environment. At times, these substances may be produced endogenously as metabolites of various processes in the body and have effects similar to those of exogenous xenobiotics. E.g. Bilirubin, bile acids, steroids, eicanosides and certain fatty acids.
Xenobiotics enter our body via numerous ways as mentioned above. There is a general tendency of the body to eliminate any substance that is foreign to its environment via immunological reactions or metabolise them to be able to get them excreted from the body. Xenobiotics, too, meet the same fate once inside the living body. As soon as they enter the body plentiful of biochemical reactions start to convert them into less toxic form and ultimately to remove them from the body. Such biochemical reactions are known as Detoxification or Biotransformation reactions.
Chemically these xenobiotic compounds are water insoluble. The main purpose of the detoxification reaction is to transform them from lipophilic hydrophobic substances to lipophobic hydrophilic ones. This biotransformation makes it easier for the body to get rid of them.
The major site for detoxification is the liver wherein the hepatocytes contain myriad of enzymes to process xenobiotic entities, altering their solubility characteristics, helping in their detoxification and metabolic activation. At times the above situation may turn around and instead increase the noxiousness of the foreign substance. Such reactions are known as entoxification reactions.
The biotransformation reactions can be divided into two phases.
The phase 1 reactions work towards making the compound hydrophilic for their easy elimination by the kidneys and to limit the toxicity of these substances. Major reactions involved are oxidation, reduction and hydrolysis wherein a functional group is either exposed or introduced, like a hydroxyl or amine or sulfhydryl group that increases their solubility in polar medium and at times generate some rective intermediates act as an acting point for phase 2 reactions. The basic reaction goes as below where a hydroxyl group has been introduced into a xenobiotic compound (RH).
RH +O2 + NADPH + H+ → R-OH +NADP+ H2O
The reactions are majorly catalysed by the enzyme Cytochrome P450 accompanied by other enzymes like aldehyde and alcohol dehydrogenase, deaminases, esterase, amidases, epoxide hydrolases.
The phase 2 reactions occur if phase 1 reactions are insufficient to get rid of these foreign substances or if a reactive metabolite has been generated. The metabolism involves conjugation of larger polar groups like glucuronide to further increase the solubility of the compound. The reactions are catalysed by the class of enzyme Transferases like uridine diphosphoglucuronosyl transferase (UGT), N-acetyl transferase (NAT), glutathione S-transferase (GST) and sulphotransferase (ST).
The combined action of these two phases renders a lipophobic hydrophilic substance from lipophilic hydrophobic ones that can be easily removed from the body.
How do they affect our body?
While inside the body these foreign substances when undergo metabolism produce some reactive intermediates that have a negative influence on the physiological processes ongoing in the cells. The toxicity of these metabolites can adversely affect a cell, tamper an immunological reaction or can even be carcinogenic leading to deadly cancers.
Some chemicals like polychlorinated biphenyls, styrene, butadiene, vinyl chloride, food stains based on acridine, combustion products of cigarette smoke, chemicals in car exhaust etc are potent mutagenic xenobiotic substances. These mutagens may either cause somatic mutations (changes in the DNA of somatic cells) leading to rapid cell aging or risk development of cancer; or gametic mutation (mutation in the DNA of egg or sperm) that may result in abortions Congenital disorder, sterility, cancer, and other adverse consequences.
Certain chemicals in food and tobacco like heterocyclic amines, N-nitrosamines, olefins, aflatoxin B1, etc. are potent carcinogens. The reactive intermediates alter the DNA that may lead to incessant cell division, tumour growth and eventually taking the body to mestastic stage.
Nitrosamines, chlorinated hydrocarbons, Toxoplasma gondii, Treponema pallidum, ionizing radiations have been known to have teratogenic effects (Teratogenicity is the ability of an exogenous factor to induce congenital malformations by unpleasantly affecting the embryogenic development). At times, the metabolism of xenobiotics into reactive and antigenic metabolite may have some dire consequences as these tend to alter the antigenicity that may cause certain allergic reactions or produce antibodies that can damage the cells by producing a heightened immunological response.
Xenobiotics are ubiquitous in nature. They are found everywhere. It is, thus, imperative to map out a strategy that would help us to monitor their presence and effect on human health. To cater the requirement biomarkers have played a role of highest importance. Biomarkers are naturally occurring molecules, gene or characteristics that help in the identification of a pathological or physiological process, disease etc.
Based on the exposure of xenobiotics, their effect on the organism and the intensity of the exposure the biomarkers can be classified into three categories. Biomarkers of exposure yields information whether the organism has been exposed to xenobiotics and their extent of exposure by measuring the DNA and protein adducts in body fluids and cells. It is followed by biomarkers of effect which help to determine the consequence of the exposure to xenobiotics on the organism by studying cytogenetic analyses and lastly, the biomarkers of susceptibility that let us measure the intensity of the effect (or response) by reviewing genetic polymorphisms.
On a concluding note
The presence of xenobiotics in nature has been marked since the embarkment of life on earth. With the establishment of the civilizations and development of society their number has only increased. Till date more than 20,000 chemical compounds have been classified as dangerous to human health. The above article has enabled to have an insight into the world of these foreign entities, their types, metabolism, effects on health and their biomonitoring. The presence and effect of these uncalled guests cannot be negated but we can be a little more careful to limit their entry into our bodily houses.