Efeito protetor do gama orizanol frente à exposição crônica ao manganês em Drosophila melanogaster

Abstract

During processing, agricultural by-products of the rice industry such as husk and bran are generated. These by-products are generally wasted in low-value applications such as incineration for energy in the case of rice husks and bran in animal feed. However, these by-products can be more valued, the oil can be extracted from rice bran, where we find the compound gamma oryzanol (ORY). ORY is a phytosterol and has important pharmacological properties described in the literature, of which we emphasize the anti-inflammatory, antioxidant and neuroprotective activities. Manganese (Mn) is an essential microelement that acts as a metallic cofactor in several biochemical and cellular functions. However, exposure to high levels of Mn causes manganism, a toxic condition characterized by symptoms that resemble Parkinson's disease (PD). Thus, in the present study, we propose to investigate the hypothesis that ORY can prevent behavioral dysfunction and biochemical changes associated with Mn exposure in Drosophila melanogaster. For that, adult flies were exposed simultaneously to manganese chloride (Mncl2) (5 mM) and ORY (25 µM) in the diet for 10 days. In the first work (Article), we found that flies exposed to Mn had a decrease in locomotor activity through negative geotaxis and open field tests, as well as a higher mortality rate, an increase in the levels of reactive species (RE) and thiobarbituric acid reactive substances (TBARs) in the head and body, when compared to the control group. Mn inhibited the activity of superoxide dismutase (SOD) and glutathione S-transferase (GST) (head), catalase (CAT) (body) and decreased levels of non-protein thiols (NPSH). The group exposed to Mn also showed a decrease in cell viability and in the activity of dehydrogenases in the body. However, ORY was able to reduce mortality as well as protect against locomotor deficits in flies exposed to Mn. Likewise, ORY normalized ER and TBARS levels in the head and body and attenuated changes in antioxidant enzyme activity. Subsequently, we investigated the effect of ORY through behavioral studies involving the non-motor symptoms of manganism, memory and learning, and involved neurotransmitters (Manuscript). ORY protected memory deficits, decreased aggressive, cleaning and anxiety events associated with Mn exposure to the levels of control animals. ORY also protected serotonin and octopamine monoamine deficits associated with Mn exposure, indicating a neuroprotective effect. In view of the above, we suggest that ORY can be considered a molecule with neuroprotective potential against Mn intoxication, given that it has a protective effect against toxicity induced by this metal in Drosophila melanogaster, both in terms of survival, motor and non-motor behavioral changes, as well as in several biochemical parameters evaluated.