Deltamethrin is responsible for health and reproduction problems both in mammals and aquatic organisms. In this study, zebrafish adults were exposed for 15 days to 0.25, 0.5, 1, and 2 μg L⁻¹ non-lethal concentrations of deltamethrin, knowing that is used worldwide on agricultural crops. We investigated the chronic effects of deltamethrin on gonads by histopathological examination, immunohistochemistry, and immunofluorescence using biomarkers for apoptosis (anti-p53, anti-H2A.XS139ph antibodies, and TUNEL assay), oxidative stress (anti-Cox4i1 antibody) and proliferation (anti-PCNA antibody). Among the histopathological changes, the apoptotic response was elevated in ovary and testis of deltamethrin exposed groups as it was seen in the IHC and IF for p53, H2A.XS139ph, and confirmed by TUNEL assay. These were observed in the case of all studied concentrations compared with the control group. Thereby, the gonadal tissue exhibited an up-regulated activity of this cell-death signaling markers, while the proliferation marker (PCNA) increased in the ovary due to its presence not only in primary growth and cortical-alveolar stage follicles but also in atretic follicles, meanwhile decreased notably in the testis. Cox4i1, a mitochondrial marker, decreased both in ovary and testis during deltamethrin treatment, probably inhibited by the overproduction of the free radicals after pesticide exposure.

The use of different commercial products that involve one or multiple active substances with specific targeted-pests control has become a widespread practice. Because of this, a severe range of significant consequences has been often reported. Among the most used pesticides worldwide are deltamethrin (DM) and imidacloprid (IMI). With a significative effect on the insect’s nervous system, DM acts on the voltage-gated sodium channels in nerve cell membranes, while IMI mimics the acetylcholine neurotransmitter by binding irreversibly to the nicotinic acetylcholine receptors. This study investigates the neurotoxic effects of sub-chronic exposure to commercial formulations of deltamethrin (DM) and imidacloprid (IMI) in adult zebrafish, both individually and in combination. The formulations used in this study contain additional ingredients commonly found in commercial pesticide products, which may contribute to overall toxicity. Fish were exposed to environmentally relevant concentrations of these pesticides for 21 days, individually or in combination. Behavioral, molecular, and histopathological analyses were conducted to assess the impact of these pesticides. Zebrafish exhibited dose-dependent behavioral alterations, particularly in the combined exposure groups, including increased erratic swimming and anxiety-like behavior. Gene expression analysis revealed significant changes in neurotrophic factors (BDNF, NGF, ntf-3, ntf-4/5, ntf-6/7) and their receptors (ntrk1, ntrk2a, ntrk2b, ntrk3a, ntrk3b, ngfra, ngfrb), indicating potential neurotoxic effects. Histopathological examination confirmed neuronal degeneration, gliosis, and vacuolization, with more severe impairments observed in pesticide mixture treatments. These findings highlight the neurotoxic potential of pesticide formulations in aquatic environments and emphasize the need for stricter regulations on pesticide mixtures and further research on pesticide interactions. Our findings emphasize that the combination of pesticides could trigger a synergistic effect by maximizing the toxicity of each compound. Thus, it is a well-known practice for pyrethroids and neonicotinoids to be used together in agriculture. Even so, its prevalence in agriculture and the need to investigate its actual impact on human health, biodiversity, and ecosystem mitigates the development of new strategies for assessing the risk and, at the same time, enhancing the effectiveness.

Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

Background: Lately, the high incidence of pesticide usage has attracted everyone’s interest due to the serious effects produced. Fipronil (FIP) is a phenylpyrazole compound that acts on the insect’s GABA neurotransmitter by inhibiting its activity. Moreover, the literature reports highlight its implication in neurodevelopmental abnormalities and oxidative stress production in different organisms. Similarly, pyriproxyfen (PYR) is known to affect insect activity by mimicking the natural hormones involved in the maturation of the young insects. The aim of the present study was to investigate the impact of the mixture of these pesticides on the tissues and behavior of zebrafish. Methods: To assess the influence of this cocktail on zebrafish, three groups of animals were randomly selected and exposed to 0, 0.05, and 0.1 mg L⁻¹ FIP and PYR mixture for five days. The fish were evaluated daily by the T-maze tests for locomotor activity and the light–dark test and recordings lasted four min. The data were quantified using the EthoVision software. Results: Our results indicated significant changes in locomotor activity parameters that showed increased levels following exposure to the mixture of FIP and PYR. On the other hand, the mixture also triggered anxiety in the zebrafish, which spent more time in the light area than in the dark area. In addition, mixture-induced histological changes were observed in the form of numerous hemosiderin deposits found in various zebrafish tissues. Conclusions: The current findings indicate that the mixture of FIP and PYR can have considerable consequences on adult zebrafish and may promote or cause functional neurological changes in addition to histological ones.

Background: Lately, the high incidence of pesticide usage has attracted everyone's interest due to the serious effects produced. Fipronil (FIP) is a phenylpyrazole compound that acts on the insect’s GABA neurotransmitter by inhibiting its activity. Moreover, literature reports highlight its impli-cation in neurodevelopmental abnormalities and oxidative stress production in different organisms. Similarly, pyriproxyfen (PYR) is known to affect insects’ activity by mimicking the natural hormones involved in the maturation of the young insects. The aim of the present study was to investigate the impact of these pesticides’ mixture on zebrafish tissues and behavior. Methods: To assess the in-fluence of this cocktail on zebrafish, three groups of animals were randomly selected and exposed to 0, 0.05 and 0.1 mg L-1 FIP and PYR mixture for 5 days. The fish were evaluated daily by the T-maze tests as locomotor activity and dark-light test and recorded for 4 minutes. The data was quantified using the EthoVision software. Results: Our results indicated significant changes in locomotor ac-tivity parameters showing increased levels following exposure to the mixture of FIP and PYR. On the other hand, the mixture also triggered anxiety in the zebrafish, which spent more time in the light area than in the dark. In addition, mixture-induced histological changes were observed in the form of numerous hemosiderin deposits found in various zebrafish tissues. Conclusions: The cur-rent findings indicate that the mixture of FIP and PYR can have considerable consequences on adult zebrafish and may promote or cause functional neurological changes in addition to histological ones.