Abstract
Aluminum chloride (AlCl3) has been used to model neurotoxicity and Alzheimer's disease (AD) like neurodegeneration in various animal models (Bondy, 2010). AlCl3 toxicity has been reported to be associated with impaired locomotor performance, learning, memory, oxidative stress and cholinergic impairment which are features seen in AD patients (Ribes et al., 2008). AlCl3 acts as a cholinotoxin (Gulya et al., 1990) and cause alterations on the cholinergic activity, a key event in the neurochemistry of AD (Rakonczay et al., 2005). Reduced cholinergic function in the brain has been shown to result in memory impairment in AD (Mukherjee et al., 2007). The use of compounds to inhibit acetylcholinesterase (AChE) activity (to reduce the hydrolysis of acetylcholine) has been a therapeutic approach in managing AD (Taylor and Radić 1994). Vitamin E has been proposed as a potential clinical intervention for AD given its antioxidant and anti-inflammatory characteristics. However, there are very few studies on its anticholinesterase activity and there also controversies as to whether vitamin E is beneficial in AD. We therefore evaluated the anticholinesterase and antioxidant activity of vitamin E in aluminium chloride induced toxicity in Drosophila melanogaster. D. melanogaster (Harwich strain, 3-5 days) were utilized for this study. In order to determine the appropriate dose of vitamin E to be utilized for this study, a 15 days survival study (where mortality rate was recorded daily) was carried out with varying dose of Vitamin E (2.5mg and 5mg). Subsequently, 2.5mg of vitamin E produced the least mortality of flies and was utilized for this study. The choice of concentration for AlCl3 was based on previous studies on aluminum toxicity in D. melanogaster [Wu et al., 2012; Ogunsuyi, 2020]. Flies (both genders) were divided into 4 groups with 50 flies per vial. Group I served as control and were reared on their cornmeal diet while group II were treated with 40mM aluminum chloride (AlCl3) via their diet. Group III flies were fed with normal diet containing 2.5mg of vitamin E while Group IV were co-administered with 40 mM AlCl3 and 2.5mg of vitamin E via their diet. The flies were maintained on these treatments at room temperature for seven (7) days. All experiments were carried out in five replicates (n=5). Negative geotaxis was carried out to assess for locomotion deficit. At the end of the experimental period, the flies were homogenized and the supernatant were used to assay for AchE activity, malonaldehyde (MDA) concentration, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities. AlCl3 induced toxicity reduced the survival rate, decreased the climbing activity, elevated MDA concentration and AChE activities of flies. SOD, CAT and GST activities were also reduced in AlCl3 treated flies. Vitamin E was able to improve the survival rate, restored AlCl3 induced reduction in climbing activity, ameliorated AlCl3 increase in AChE activity and MDA concentration in flies. In addition, Vitamin E attenuated AlCl3 induced inhibition of SOD, CAT and GST activities. This study has shown that Vitamin E has both antioxidant and anticholinesterase activities and can be regarded as a therapeutic agent against AlCl3 induced toxicity and associated diseases.
