Xenobiotics

Xenobiotics are chemical substances that are foreign to a biological system. They include pharmaceuticals, environmental pollutants, pesticides, industrial chemicals, and many other synthetic compounds not normally produced by the organism. Xenobiotics can enter the body through ingestion, inhalation, skin contact, or exposure to the environment, and they may interact with biological pathways in various ways.

Most organisms metabolize xenobiotics to facilitate detoxification and elimination. In vertebrates, metabolism commonly proceeds in two phases: Phase I reactions such as oxidation, reduction, or hydrolysis, often mediated by cytochrome P450 enzymes, introduce or reveal functional groups. Phase II reactions involve conjugation, including glucuronidation, sulfation, acetylation, and conjugation with glutathione, which increase water solubility for excretion by the kidneys or biliary system. Some xenobiotics undergo bioactivation, where metabolic steps produce more reactive or toxic species.

Xenobiotics can interact with cellular receptors and signaling pathways. Aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) regulate the expression of metabolizing enzymes and transporters in response to foreign compounds. Such interactions influence toxicity and the body's ability to clear xenobiotics. Not all xenobiotics are harmful; many are therapeutic agents or benign environmental substances, but others are persistent, bioaccumulative, or mutagenic and pose health or ecological risks.

Risk assessment and regulatory frameworks study xenobiotics to manage exposure, monitor environmental contamination, and guide public health decisions. Persistent organic pollutants, endocrine disruptors, and pharmaceutical residues are common concerns. In ecosystems, microbial degradation and biotransformations can alter xenobiotics, influencing their fate and effects. Understanding xenobiotics spans pharmacology, toxicology, environmental science, and risk management.