Novel Hexahydropyridoindole Derivative as Prospective Agent Against Oxidative Damage in Pancreatic βCells

Lucia      Rackova; Ahmet      Cumaoglu; E.      Umit Bagrιacιk; Milan      Stefek; Pierre      Maechler; Cimen      Karasu

Abstract

The potential protective effect of (±)-8-methoxy-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid ethyl ester (II) was assessed against hydrogen peroxide (H2O2)-cytotoxicity in rat pancreatic INS-1E β cells and compared with the effect of the related pyridoindole, stobadine (I), a promising indole-type reference antioxidant. Only pre-treatment with the compound (II) led to a significant preservation of the metabolic and secretory functions of the cells exposed to H2O2.

The caspase-9 and -3 activities, as well as the early apoptotic changes of plasma membrane, were suppressed in the cells pre-incubated with both of compounds tested. However, only pyridoindole (II) inhibited profoundly the time-delayed apoptotic changes,

These results suggest that pyridoindole (II) characterized by enhanced intrinsic antioxidant efficiency, may protect ?? cells against cytotoxic effects of H2O2, involved in the development of both type 1 and type 2 diabetes.

Keywords: Indole antioxidant, pancreatic cells, oxidative stress, diabetes, hexahydro-pyrido, (H2O2)-cytotoxicity, promising indole-type, metabolic and secretory functions of the cells, exposed to H2O2, pyridoindole (II)