7-chloro-4-(phenylselanyl) quinoline co-treatment prevent oxidative stress in diabetic-like phenotype induced by hyperglycidic diet in Drosophila melanogaster.

The goals of this work were to evaluate the effects produced by a hyperglycidic diet (HD) on Drosophila melanogaster and to verify the protective effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on this model. Adult flies were divided into eight groups of 50 flies each: (1) RD, (regular diet) (2) RD + 4-PSQ (25 µM), (3) HD 5%, (4) HD 10%, (5) HD 30% (6) HD 5% + 4-PSQ (25 µM), (7) HD 10% + 4-PSQ (25 µM) and (8) HD 30% + 4-PSQ (25 µM). Flies were exposed to a diet containing sucrose and or 4-PSQ for ten days, according to each group. At the end of treatment survival rate, longevity, hatch rate, food intake, glucose and triglyceride levels, as well as, some markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) activities, protein thiol (PSH) and non-protein levels (NPSH) and cell viability assays (Resazurin and MTT) were evaluated. It was observed that HD's consumption was associated with lower survival of the flies, lower longevity, and increased levels of glucose, triglycerides, TBARS and increased SOD activities and CAT activities. Treatment with 25 µM 4-PSQ increased the satiety of flies, increased survival, reduced glucose, triglyceride and TBARS levels, increased hatching, and normalized SOD and CAT activities. These results suggest that 25 µM 4-PSQ had a potential antioxidant effect and provided greater satiety by attenuating the effects of high HD consumption on this model.

7-chloro-4-(phenylselanyl) quinoline prevents dopamine depletion in a Drosophila melanogaster model of Parkinson's-like disease.

Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson's-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 µM), [3] ROT (500 µM), and [4] 4-PSQ (25 µM) + ROT (500 µM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.