Characterization of release profile of ornithine carbamoyltransferase from primary rat hepatocytes treated with hepatotoxic drugs: Implications for its unique potential as a drug-induced liver injury biomarker

Drug Metabolism and Pharmacokinetics
Tomomi FurihataKan Chiba

Abstract

Ornithine carbamoyltransferase (OCT) is a mitochondrial protein expressed primarily in the liver. It has been shown that, like alanine aminotransferase (ALT), OCT is released from damaged hepatocytes in rats and humans, which has given rise to the possibility that OCT might provide a diagnostic biomarker of various forms of liver damage, including drug-induced liver injury (DILI). However, OCT release characteristics in DILI, as well as their diagnostic advantages, remain elusive. Therefore, this study aimed at clarifying whether and how OCT is released from rat primary hepatocytes in vitro using seven potentially hepatotoxic drugs. The results showed that OCT releases from damaged hepatocytes were observed for all tested drugs, and that those releases were not associated with mitochondrial membrane proteins. It should be underscored that the release dynamics were significantly larger than those of ALT. Furthermore, unlike ALT, the maximum OCT release levels showed differences depending on the drug being tested, suggesting that OCT release was susceptible to toxicity mechanisms. Taken together, these unique release characteristics highlight the possibility that OCT could provide a promising DILI biomarker that might contribute ...Continue Reading

References

Jul 29, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Hiroshi MurayamaAtsuo Nagata
Nov 1, 2007·Nature Reviews. Drug Discovery·Russell A WilkeRonald M Krauss
Feb 19, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Hiroshi MurayamaAtsuo Nagata
Feb 12, 2009·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Hajime TakikawaMorikazu Onji
Feb 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Daniel J AntoineB Kevin Park

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.