Induction of Antioxidant Enzymes by Curcumin and Its Analogues in Human Islets Implications in Transplantation

Objectives: The survival of transplanted human islets is hampered by the quality of islets, which is affected by oxidative stress during isolation. The objective of this study was to determine if curcumin and its analogues could induce antioxidant enzymes in A cells of human islets. Methods: The expression of antioxidant enzymes in isolated human islets exposed to curcuminoids was determined at the messenger RNA levels by real-time quantitative reverse transcription-polymerase chain reaction using Taqman probes and at the protein level by Western blot analysis. Double immunofluorescent staining of islets was carried out to determine the induction of antioxidant enzymes in A cells. Results: Curcuminoids induced the expression of heme oxygenase 1; modulatory subunit of gamma-glutamyl-cysteine ligase; and NAD(P)H: quinone oxidoreductase 1 at the messenger RNA levels by 2- to 12-fold and at the protein levels by 2- to 6-fold in human islets. Increased expression of antioxidant enzymes was seen in A cells of islets as shown by immunofluorescent staining. Curcuminoids also increased the islet content of glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase) and the basal insulin secretion and protected them from oxidative stress. Conclusions: Our observations suggest that curcumin or its analogues could be used to induce cellular defense against oxidative stress and improve islet transplantation outcomes.