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Neurobehavioral Toxicity Induced by Carbendazim in Rats and the Role of iNOS, Cox-2, and NF-κB Signalling Pathway

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Abstract

Carbendazim (CBZ) is one of the most common fungicides used to fight plant fungal diseases, otherwise, it leaves residue on fruits, vegetables, and soil that contaminate the environment, water, animal, and human causing serious health problems. Several studies have reported the reproductive and endocrine pathological disorders induced by CBZ in several animal models, but little is known about its neurotoxicity. So that, the present study aimed to explain the possible mechanisms of CBZ induced neurotoxicity in rats. Sixty male Wistar rats were divided into 4 groups (n = 15). Group (1) received normal saline and was kept as the negative control group, whereas groups (2, 3, 4) received CBZ at 100, 300, 600 mg/kg b.wt respectively. All rats received the aforementioned materials daily via oral gavage. Brain tissue samples were collected at 7, 14, 28 days from the beginning of the experiment. CBZ induced oxidative stress damage manifested by increasing MDA levels and reducing the levels of TAC, GSH, CAT in some brain areas at 14 and 28 days. There were extensive neuropathological alterations in the cerebrum, hippocampus, and cerebellum with strong caspase-3, iNOS, Cox-2 protein expressions mainly in rats receiving 600 mg/kg CBZ at each time point. Moreover, upregulation of mRNA levels of NF-κB, TNF-α, IL-1B genes and downregulation of the transcript levels of both AchE and MAO genes were recorded in all CBZ receiving groups at 14 and 28 days especially those receiving 600 mg/kg CBZ. Our results concluded that CBZ induced dose- and time-dependent neurotoxicity via disturbance of oxidant/antioxidant balance and activation of NF-κB signaling pathway. We recommend reducing the uses of CBZ in agricultural and veterinary fields or finding other novel formulations to reduce its toxicity on non-target organisms and enhance its efficacy on the target organisms.

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Data Availability

All data are available on request.

Abbreviations

AchE:

Acetylcholinesterase

ACTB:

Beta-actin housekeeping gene

ATP:

Adenosine triphosphate

b.wt:

Body weight

CA:

Cornu Ammonis

CAT:

Catalase

CBZ:

Carbendazim

Cox-2:

Cyclooxygenase-2

DNA:

Deoxyribonucleic acid

EDTA:

Ethylene diamine tetra acstic acid

GSH:

Glutathione

GTP:

Guanosine triphosphate

H&E:

Hematoxylin & Eosin

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

LAF:

Lymphocyte-activating factor

LD50:

Lethal dose-50

MAO:

Monoamine oxidase

MAPK:

Mitogen-activated protein kinase

MDA:

Malondialdehyde

MMP:

Matrix metalloproteinase

mRNA:

Messenger ribonucleic acid

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

PBS:

Phosphate buffer saline

PGE2:

Prostaglandine E2

ROS:

Reactive oxygen species

Rt-PCR:

Real-time polymerase chain reaction

SEM:

Standard error of mean

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor-alpha

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Authors and Affiliations

  1. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt

    Yasmin A. Ebedy, Eman I. Hassanen & M. O. Elshazly

  2. Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Ahmed M. Hussien

  3. Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Marwa A. Ibrahim

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  1. Yasmin A. Ebedy
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  2. Eman I. Hassanen
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  3. Ahmed M. Hussien
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Correspondence to Eman I. Hassanen.

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Ebedy, Y.A., Hassanen, E.I., Hussien, A.M. et al. Neurobehavioral Toxicity Induced by Carbendazim in Rats and the Role of iNOS, Cox-2, and NF-κB Signalling Pathway. Neurochem Res 47, 1956–1971 (2022). https://doi.org/10.1007/s11064-022-03581-5

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