Disclosed is the identification of four separate plasma protein biomarkers found to be S-glutathionylated upon exposure to a formulation containing oxidized glutathione (NOV-002), along with a method for detection of the modified proteins. S-glutathionylation is a reversible reaction in which glutathione is bound to a cysteine residue on a target protein and occurs in response to oxidative stress. Oxidative stress can be toxic and can be induced by the administration of certain drugs, particularly anticancer agents such as Cisplatin, Busulfan and others. Therefore, these biomarkers will be useful in monitoring the oxidative stress produced by anticancer agents as well as the pharmacological activity of S-glutathionylation-inducing agents such as NOV-002.
Investigators at the Medical University of South Carolina performed both in vivo and ex vivo studies with mice using NOV-002. Mice were administered NOV-002 intravenously and plasma samples were recovered. Upon analysis of the samples four proteins were found to be S-glutathionylated, and their identities were characterized. In further studies plasma was removed from the animals and treated ex vivo with NOV-002. It was confirmed that the same proteins were modified in this set of experiments as well.