Citrulline as a Biomarker of GI Toxicity

Citrulline is produced by small bowel enterocytes, with circulating citrulline levels correlating with enterocyte mass. Changes in enterocyte number (or in some cases function) are therefore reflected in plasma levels. As a result, citrulline levels may be a biomarker for various GI syndromes, including damage induced by radiation or chemotherapy or hyperplastic conditions.

A recent paper by Bujold et al. (Radiation Research vol. 186) examined the response in mice, mini-pigs and rhesus macaques and supports several previous publications by Jace Jones and colleagues (mice and rhesus macaques) regarding the use of citrulline as a biomarker for GI-Acute Radiation Syndrome (GI-ARS).

Circulating levels decrease as a result of prior intestinal damage, hence citrulline is a delayed, correlative, rather than a predictive biomarker. Plasma citrulline levels decrease/recover in a time and dose dependent manner but the sensitivity is such that it cannot discriminate between high doses of radiation and is not predictive of recovery/survival.

Serial sampling from the same individual after insult can indicate GI recovery. In rhesus macaques a persistently depressed citrulline level correlated with long term incomplete GI recovery (Delayed Effects of Acute Radiation Syndrome - DEARE).

Procedures that interfere with intestinal function, such as feeding, anesthesia, immunocompromization and infection can confound the data, as can the time of sampling (due to the circadian rhythm).

At Epistem we offer rodent models of GI toxicity, including radiation and chemotherapy evaluation.

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In addition, our analytical services include measures of enterocyte loss / recovery (including characterization of the target cell population and response kinetics), diarrhoea severity, mucosal permeability, cytokine (tissue and plasma) changes and inflammatory cell responses via FACS analyses and complete blood count measures. Get in touch to discuss your needs and how we might help you.

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