Magainin-AM2 inhibits sucrose-induced hyperglycaemia, oxidative stress, and cognitive dysfunction in Drosophila melanogaster.

ABSTRACT

Hyperglycaemia-induced oxidative stress plays significant roles in the development of type 2 diabetes and its complications. This study investigates effects of magainin-AM2 on high-sucrose diet induced redox imbalance and cognitive impairment in Drosophila melanogaster. Effects of various concentrations of sucrose, magainin-AM2 or a combination of both agents on mortality, eclosion rate, generation of reactive oxygen and nitrogen species, activities of antioxidant enzymes, thiol system, and markers of cognitive functions in control and treated flies were examined. Results showed that the exposure of flies to high sucrose (30 %-60 % w/w) diet increased mortality rate (38-67 %, P < 0.001) and levels of glucose (1.8-1.9-fold, P < 0.001), hydrogen peroxide (1.4-1.5-fold, P < 0.01) and nitrite/nitrate (1.2-fold, P < 0.01). Decreased levels of total thiol (53-59 %, P < 0.01), non-protein thiols (59-63 %, P < 0.01), catalase activities (39-47 %, P < 0.01-0.05) and glutathione-s-transferase activities (31-43 %, P < 0.01-0.05) were also observed. Magainin-AM2 (0-10 µM/kg diet) did not affect fly mortality rate, levels of hydrogen peroxide and nitrite/nitrate, and activities of catalase and glutathione-s-transferase. However, the peptide produced a dose-dependent increase in total thiol 1.2-1.6-fold, P < 0.001-0.01)and increases non-protein thiol levels at 10 µM/kg diet (2.0-fold, P < 0.01). Magainin-AM2 inhibited sucrose-induced elevation of glucose (55-70 %, P < 0.001), hydrogen peroxide (11-12 %, P < 0.01) and nitrite/nitrate (20-34 %, P < 0.01-0.05). The peptide prevented sucrose-induced reduction in total and non-protein thiols (1.9-2.0-fold, P < 0.05) levels and activities of catalase (2.3-3.1-fold, P < 0.001) and glutathione-s-transferase (1.8-2.8-fold, P < 0.001-0.05). Magainin-AM2 inhibited sucrose-induced reduction in acetylcholinesterase activities (3.6-4.0-fold, P < 0.001), eclosion rate (18 %, P < 0.001) and negative geotaxis (1.3-14-fold, P < 0.001). These results indicate that beneficial actions of magainin-AM2 may also involve the prevention of hyperglycaemia-induced oxidative damage and encourage its further development as an anti-diabetic agent.