Insight into Drugs Induce Liver Toxicity

In the human body, the liver is a vital organ. It has a variety of activities, including metabolism, immunity, digestion, detoxification, and vitamin storage, among others.

Non-reactive chemicals are thought to be biotransformed in two phases: functionalization, which involves the use of oxygen to create a reactive site, and conjugation, which involves the addition of a water-soluble group to the reactive site. Phase I and phase II detoxification refer to the two phases of functionalization and conjugation, respectively. As a result, a lipophilic chemical that cannot be expelled in urine is biotransformed into a water-soluble compound that can be eliminated in urine. The liver is the primary organ engaged in drug and xenobiotic metabolism and detoxification.

There are three stages of drug metabolism. The superfamily of CYP monooxygenases is involved in phase I drug oxidation. Phase I reactions can convert prodrugs to active forms and xenobiotics to benign molecules, but they can also increase the toxicity of the metabolites in some cases. Phase II processes include sulfation, methylation, and glucuronidation to improve the solubility of oxidised metabolites, which are released by phase III drug transporters found in the membranes of hepatocytes, intestinal cells, kidneys, and other organs for excretion.

A drug-induced liver injury (DILI) is a liver injury caused by exposure to a medication or a non-infectious toxic substance that causes organ dysfunction in varying degrees.

From a pharmacological standpoint, two types of DILI can be distinguished: dose-dependent and dose-independent or idiosyncratic. Direct toxicity, also known as dose-dependent DILI, is predictable, repeatable, and develops quickly after consuming a dose that exceeds a recognised hazardous threshold. The damage entity is proportional to the dose given. DILI that is idiosyncratic, on the other hand, is unpredictable and frequently occurs at therapeutic levels. The quantity of damage is not necessarily proportionate to the injected dose, and the time it takes for harm to appear varies greatly.

DILI can cause mitochondrial impairment, biliary efflux inhibition, lysosomal impairment, endoplasmic reticulum stress, production of reactive metabolites leading to chemical stress, oxidative stress, and protein modification, as well as triggering innate and adaptive immune responses and causing cytokine activation. All of these manifestations have the potential to harm the liver.

Acute hepatic necrosis, elevated enzymes, acute hepatitis, cholestatic hepatitis, mixed hepatitis, chronic hepatitis, bland cholestasis, acute fatty liver disease, lactic acidosis, hepatic failure, nonalcoholic fatty liver disease, sinusoidal obstruction syndrome, and nodular regenerative hyperplasia are all phenotypes of DILI.

Author(s) Details

Dheaa Shamikh Zageer
Forensic DNA Center For Research and Training/ Al-Nahrain University, Baghdad, Iraq.

Sundus Fadhil Hantoosh
Forensic DNA Center For Research and Training/ Al-Nahrain University, Baghdad, Iraq.

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