Neurotrophic factors comprise essential secreted proteins that have several functions in neural and non-neural tissues, mediating the development, survival and maintenance of peripheral and central nervous system. Therefore, neurotrophic factor issue has been extensively investigated into the context of neurodegenerative diseases. Alzheimer's disease and Parkinson's disease show changes in the regulation of specific neurotrophic factors and their receptors, which appear to be critical for neuronal degeneration. Indeed, neurotrophic factors prevent cell death in degenerative processes and can enhance the growth and function of affected neurons in these disorders. Based on recent reports, this review discusses the main findings related to the neurotrophic factor support – mainly brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor – in the survival, proliferation and maturation of affected neurons in Alzheimer's disease and Parkinson's disease as well as their putative application as new therapeutic approach for these diseases management.
San Jose scale, Diaspidiotus perniciosus (Comstock), is a serious pest in Chilean apple tree orchards, and a number of organophosphate insecticides were used to control them for decades. Recently, control failures with these insecticides were reported and linked to insecticide resistance development. In this study, 40 San Jose scale field populations were collected and their susceptibility to two commonly used organophosphate insecticides, that is chlorpyrifos and methidathion, was assessed. The obtained bioassay data suggest moderate levels of resistance to both insecticides when compared to a reference susceptible strain. The highest resistance ratio (RR) detected for chlorpyrifos and methidathion was 31‐fold and 11‐fold, respectively. The bioassay results suggest the occurrence of a significant cross‐resistance between both compounds. Biochemical measurements revealed a role for esterases in conferring resistance to organophosphates, but not modified acetylcholinesterase. The spatial spread and extend of insecticide resistance were also evaluated. Our result shows that no autocorrelation can be assumed, and then, insecticide resistance is caused by random factors.
The inhibition of acetylcholinesterase (AChE) is a common outcome caused by organophosphorus (OPs) intoxication. Although inconsistent, the standard treatment consists of a muscarinic receptor antagonist (atropine) and AChE‐reactivating molecules such as oximes. This study proposes to test unpublished compounds which contain the moieties of isatin and/or oxime have protective effects against the toxicity induced by malathion in two animal models: Artemia salina and Rattus norvegicus (Wistar rats). The lethality was assessed in A salina, and the calculated LD50 to (3Z)‐5‐chloro‐3‐(hydroxyimino) indolin‐2‐one oxime (Cℓ‐HIN) and 2‐(5‐chloro‐2‐oxoindolin‐3‐ylidene)‐hydrazinecarbothioamide (Cℓ‐OXHS) was higher than 1000 µM while to 3‐(phenylhydrazono) butan‐2‐one oxime (PHBO) was 38 µM. Our screening showed that Cℓ‐HIN seems to be the most promising molecule, with low toxicity to A salina, protection against mortality (with or without atropine) and AChE inhibition induced by malathion. Similarly, the oral administration of 300 mg/kg of Cℓ‐HIN induced low or no toxicity in rats. The plasma butyrylcholinesterase (BChE) and cortical AChE activities were reactivated by Cℓ‐HIN (50 mg/kg, p.o.) in rats exposed to malathion (250 mg/kg, i.p). No difference was observed in paraoxonase‐1 (PON‐1) activity among groups treated. In conclusion, Cℓ‐HIN restored the cholinesterase activities inhibited by malathion in A salina and rats with low toxicity in both. Thus, the data provide evidence that Cℓ‐HIN, a compound that combines isatin and oxime functional groups, is safe and has important properties to reactivate the cholinesterases inhibited by malathion. In addition, we demonstrate the importance of a preliminary assessment in an alternative model in order to reduce the use of mammalians in drug discovery.
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