Toxic effect and genotoxicity of the semisynthetic derivatives dillapiole ethyl ether and dillapiole n-butyl ether for control of Aedes albopictus (Diptera: Culicidae)

Highlights

• The compounds 1KL39-B and 1KL43-C were toxic and genotoxic on A. albopictus.

• Aedes albopictus eggs and larvae exposed to the 1KL39-B and 1KL43-C exhibited high mortality.

• The two semi-synthetics of dillapiole are a potential alternative for A. albopictus control.

Abstract

Two derivatives of dillapiole, dillapiole ethyl ether (1KL39-B) and butyl ether-n dillapiole (1KL43-C), were studied for their toxicity and genotoxicity against Aedes albopictus, to help develop new strategies for the control of this potential vector of dengue and other arboviruses, because it is resistant to synthetic insecticides. Eggs and larvae exposed to different concentrations of 1KL39-B (25, 30, 50, 70, and 80 μg/mL) and of 1KL43-C (12.5, 20, 25, 30 and 40 μg/mL) exhibited toxicity and susceptibility, with 100% mortality. The LC₅₀ was 55.86 ± 1.57 μg/mL for 1KL39-B and 25.60 ± 1.24 μg/mL for 1KL43-C, while the LC₉₀ was 70.12 μg/mL for 1KL39-B and 41.51 μg/mL for 1KL43-C. The gradual decrease in oviposition of the females of the G₁ to G₄ generations was proportional to the increase in concentrations of these compounds, which could be related to the cumulative effect of cell anomalies in neuroblasts and oocytes (P < 0.05), including micronuclei, budding, multinucleated cells and nuclear bridges. These findings showed that both 1KL39-B and 1KL43-C can serve as potential alternatives in the control of A. albopictus.

Introduction

Aedes (Stegomyia) albopictus Skuse, 1894 is a mosquito with the potential to transmit 26 arboviruses, including Dengue virus (DENV), Chikungunya virus (CHIKV) and Zika virus (ZIKV) [1], [2], [3], [4], [5], [6]. Dengue affects over 50 million people every year in several countries, accounting for high morbidity among the sick. [7] Although there is no record of the involvement of A. albopictus in the transmission of arboviruses to humans in Brazil, this species is of great epidemiological importance in this transmission process in Asia and Africa [8], [9], [10], [11]. Furthermore, A. albopictus can serve as a bridge between the wild and urban cycles of yellow fever because of its ease of adapting to different environments [12].

A. albopictus is native to Asia and its spread around the world began in 1980 [12], [13]. The first record of this mosquito in Brazil was in Rio de Janeiro in 1986 [14] and in the Amazon region in 1996 [15]. It has a rural habitat [16], [17], but it is also found in peri-urban regions and is generally associated with areas with vegetation [18]. The introduction of people in these areas increases the risk of arbovirus transmission by A. albopictus [3].

Synthetic insecticides are commonly used to control mosquito vectors, with the main ones being organochlorines, organophosphates, carbamates and pyrethroids [19], [20], [21], [22]. These insecticides block sodium and potassium channels [23], [24], act as GABA receptor antagonists [23], [25] or inhibit the enzyme acetylcholinesterase, leading to accumulation of acetylcholine [26], [27], which interferes with the transmission of nerve impulses, causing the death of the mosquito [23], [25], [26]. However, mosquitoes acquire resistance to most synthetic insecticides used [23], [24], [26], [27], [28].

Natural plant-based compounds, such essential oils or their components have been studied as alternatives in vector control [29], [30], [31]. Dillapiole is a compound found in the essential oil of the long pepper plant (Piper aduncum), which has been tested for its potential in the control of A. aegypti [32]. Another approach is to use semisynthetic compounds of dillapiole and other natural products, to improve the physical and chemical properties of these substances and to achieve better efficacy [32], [33], [34], [35].

Cytogenetics has helped to characterize anomalies in mosquito cells exposed to genotoxic substances in both in vitro and in vivo assays [32], [35]. The evaluation of nuclear abnormalities uses tools such as the micronucleus test in vivo, considered standard in genotoxicity assays [32], [35], [36], where it is a quick and easy way to determine the genotoxic effects of certain compounds on a given organism [37].

Considering the data in the literature, semisynthetic derivatives of dillapiole as well as dillapiole, at concentrations over 80 μg/mL are toxic to A. aegypti, but when used at much lower concentrations, DNA damage is observed, along with a decrease in fertility [35]. Aedes albopictus lacks similar data regarding alternative insecticides for vector control for mosquitoes in general. Accordingly, the aim of the present study was to evaluate the genotoxicity of 1KL39-B and 1KL43-C in neuroblasts and oocytes of exposed specimens of A. albopictus, and also to determine if the frequency of alterations was related to a decrease in fertility of individuals exposed to these compounds and of their descendants.