Alterations of mitochondrial electron transport chain and oxidative stress induced by alkaloid-like α-aminonitriles on Aedes aegypti larvae.

Autor: Borrero Landazabal MA; Grupo de Investigaciones en Bioquímica y Microbiología (GIBIM), Escuela de Química, Universidad Industrial de Santander, Bucaramanga A.A. 678, Colombia; Centro de Investigaciones en Enfermedades Tropicales (CINTROP), Facultad de Salud, Escuela de Medicina, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Bucaramanga, A.A. 678, Colombia., Carreño Otero AL; Laboratorio de Química Orgánica y Biomolecular, Escuela de Química (LQOBio), Universidad Industrial de Santander, Bucaramanga A.A. 678, Colombia., Kouznetsov VV; Laboratorio de Química Orgánica y Biomolecular, Escuela de Química (LQOBio), Universidad Industrial de Santander, Bucaramanga A.A. 678, Colombia., Duque Luna JE; Centro de Investigaciones en Enfermedades Tropicales (CINTROP), Facultad de Salud, Escuela de Medicina, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Bucaramanga, A.A. 678, Colombia., Mendez-Sanchez SC; Grupo de Investigaciones en Bioquímica y Microbiología (GIBIM), Escuela de Química, Universidad Industrial de Santander, Bucaramanga A.A. 678, Colombia. Electronic address: scmendez@uis.edu.co.
Jazyk: angličtina
Zdroj: Pesticide biochemistry and physiology [Pestic Biochem Physiol] 2018 Jan; Vol. 144, pp. 64-70. Date of Electronic Publication: 2017 Nov 22.
DOI: 10.1016/j.pestbp.2017.11.006
Abstrakt: Aedes aegypti mosquitoes are responsible for dengue, chikungunya, and Zika virus transmission in tropical and subtropical areas around the world. Due to the absence of vaccines or antiviral drugs for human treatment, the majority of control strategies are targeted at Ae. aegypti elimination. Our research on mosquito control insecticidal agents has previously shown that the alkaloid girgensohnine and its analogues (α-aminonitriles) present in vitro acetylcholinesterase inhibition and in vivo insecticidal activity against Ae. aegypti. However, acetylcholinesterase inhibition may not be the only mechanism of action behind these effects. On this basis, the principal aim of this study was to elucidate the possible action mode of four α-aminonitriles on Ae. aegypti by studying other important enzymatic targets, such as mitochondrial electron transport chain complexes, catalase, and superoxide dismutase, key oxidative stress enzymes. Mitochondria were isolated from Ae. aegypti larvae by differential centrifugation, stored at -70°C, and fragmented using ultrasound for 10min. The effects of α-aminonitriles (1 to 4) over enzymatic activities were evaluated using concentrations of 8nM, 2μM, 8μM, and 40μM. Results indicated that α-aminonitriles caused significant NADH dehydrogenase and succinate oxidase inhibition (~44% at the highest concentration tested). Succinate dehydrogenase and cytochrome c oxidase activities were found to increase (162% and 106% at 40μM, respectively). It was also observed that these compounds produced catalase inhibition and thus prevented H 2 O 2 reduction, which induced the formation of reactive oxygen species (ROS). Moreover, NBT assay showed that compounds 3 and 4 (with 2-(pyrrolidin-1-yl) acetonitrile as substituent) increased by approximately 50% the O 2 ●- concentration in the mitochondrial respiratory chain. It was concluded that the tested compounds act as complex I inhibitors by blocking electron transport and causing electron leak, possibly between complex I and III. Furthermore, α-aminonitriles inhibited catalase activity; compounds 1 and 2 (with piperidine fragment) inhibited glutathione reductase activity and further promoted the accumulation of ROS, which probably induced oxidative stress.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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