Justina Grigalyte

• BSc (Hons) Pharmacology
• Carboxylic acid drugs and chemicals – investigating their potential to trigger idiosyncratic liver injury and an auto-immune liver disease

Primary biliary cholangitis (PBC) is an autoimmune-associated chronic liver disease triggered by carboxylate-containing xenobiotics mimicking lipoic acid, leading to a loss of tolerance to the lipoic acid conjugated regions of the mitochondrial branched chain α-ketoacid dehydrogenase complex, typically to the E2 component (PDC-E2). It is diagnosed by the presence of antibodies to PDC-E2 (anti-mitochondrial antibodies). Recent work in the supervisor’s laboratory has demonstrated that ionic liquid chemicals, when metabolised to a carboxylic acid, may be a hazard for development of PBC. However, any drug, chemical (or a metabolite) structurally similar to lipoic acid is capable of being incorporated into the branched chain α-ketoacid dehydrogenase complex antigens, may be a potential hazard for triggering injury and disease.

Funding source: British Toxicology Society

Project supervisor: Professor Matthew Wright