Abstract
Fipronil (FIP) is an N-phenylpyrazole insecticide that is used extensively in public health and agriculture against a wide range of pests. Exposure to FIP is linked to negative health outcomes in humans and animals including promoting neuronal cell injury, which results in apoptosis through the production of reactive oxygen species (ROS). Therefore, the purpose of the current study was to investigate the neuroprotective effects of cerium oxide nanoparticles (CeNPs) on neuronal dysfunction induced by FIP in albino rats. Male rats were randomly classified into four groups: control, FIP (5 mg/kg bwt), CeNPs (35 mg/kg bwt), and FIP + CeNPs (5 (FIP) + 35 (CeNPs) mg/kg bwt), which were treated orally once daily for 28 consecutive days. Brain antioxidant parameters, histopathology, and mRNA expression of genes related to brain function were evaluated. The results revealed oxidative damage to brain tissues in FIP-treated rats indicated by the elevated levels of malondialdehyde (MDA) and nitric oxide (NO) levels and reduced activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). On the other hand, the FIP’s group that was treated with CeNPs showed decrease in MDA and NO levels and increase in SOD and GPx enzymes activity. Besides, FIP-treated rats showed decreased butyrylcholinesterase (BuChE) activity in comparison to the FIP + CeNPs group. Moreover, FIP caused up-regulation of the expression of neuron-specific enolase (NSE), caspase-3, and glial fibrillary acidic protein (GFAP) but down-regulation of B-cell lymphoma-2 (BCL-2) expression. But the FIP + CeNPs group significantly down-regulated the GFAP, NSE, and caspase-3 and up-regulated the gene expression of BCL-2. Additionally, the FIP-treated group of rats had clear degenerative lesions in brain tissue that was reversed to nearly normal cerebral architecture by the FIP + CeNPs treatment. Immunohistochemical examination of brain tissues of rats-treated with FIP showed abundant ionized calcium-binding adaptor molecule 1 (Iba-1) microglia and caspase-3 and apoptotic cells with nearly negative calbindin and synaptophysin reaction, which were countered by FIP + CeNPs treatment that revealed a critical decrease in caspase-3, Iba-1 reaction with a strong calbindin positive reaction in most of the Purkinje cells and strong synaptophysin reaction in the cerebrum and cerebellum tissues. Based on reported results herein, CeNPs treatment might counteract the neurotoxic effect of FIP pesticide via an antioxidant-mediated mechanism.
Highlights
Fipronil (FIP; 5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)trifluoromethylsulfinyl pyrazole-3-carbonitrile) is a wide range N-phenylpyrazole insecticide that is extensively used around the world toward the management of a wide spectrum of insects, indoors pests, agricultural pests, and ectoparasitic in veterinary clinical field (Jennings et al, 2002; Bonneau et al, 2015; McMahen et al, 2015; Mossa et al, 2015)
The excessive generation of reactive oxygen species (ROS) could affect the permeability of the mitochondrial membrane decreasing its potential and inhibit the pro-survival gene expression of for example the B-cell lymphoma-2 (BCL-2), which subsequently contributes to cellular apoptosis due to the activation of the caspase cascade (Orrenius et al, 2007)
The antioxidant activity that is based on the ratio of Ce3+/Ce4+ on the surface of the Cerium oxide nanoparticles’ (CeNPs) structure works as catalase mimetic activity, hydroxyl scavenging property (Dowding et al, 2013), nitric oxide scavenging property, and superoxide dismutase mimetic activity (Xu and Qu, 2014)
Summary
Fipronil (FIP; 5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)trifluoromethylsulfinyl pyrazole-3-carbonitrile) is a wide range N-phenylpyrazole insecticide that is extensively used around the world toward the management of a wide spectrum of insects, indoors pests, agricultural pests, and ectoparasitic in veterinary clinical field (Jennings et al, 2002; Bonneau et al, 2015; McMahen et al, 2015; Mossa et al, 2015). It was reported that FIP induced neurotoxicity through the initiation of oxidative stress and mitochondrial damages (Seydi et al, 2021). It caused oxidative stress and cellular DNA deterioration in the cell culture of rats’ pheochromocytoma (Lassiter et al, 2009). FIP triggered neuronal cell death and induced apoptosis that was mediated primarily by the generation of reactive oxygen species (ROS) and activation of mitogen-activated protein kinase (MAPK) members followed by activation of the intrinsic apoptotic pathway (Ki et al, 2012). The aim of this research was, to examine the neuroprotective activity of CeNPs on neurotoxicity caused by FIP in albino rats
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