Which organ serves as the main site for detoxification and metabolism of xenobiotics?

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Detoxification and metabolism of xenobiotics occur primarily in the liver. The liver’s hepatocytes are rich in detoxifying enzymes, especially the cytochrome P450 family, which carry out Phase I reactions like oxidation, reduction, and hydrolysis to introduce reactive or polar groups. This is followed by Phase II conjugation reactions such as glucuronidation, sulfation, and glutathione conjugation, which attach polar groups to increase water solubility and facilitate elimination. The liver also receives blood from the digestive tract via the portal vein, so many foreign compounds encounter hepatic metabolism before reaching the systemic circulation (first-pass metabolism). While other organs contribute to handling some substances—kidneys for excretion of soluble metabolites, lungs for volatile compounds—the liver is the central organ for detoxification and metabolism of xenobiotics. The spleen, by contrast, is mainly involved in immune and hematologic functions rather than xenobiotic processing.