الفهرس 
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Abstract
Carbendazim (CBZ) is a broad-spectrum fungicide and widely used in agriculture, but its residues in the environment have several toxic effects on various body organs. Some studies revealed the adverse effect of CBZ on some organs, but its detailed toxicity mechanism has not been elucidated yet. Nanotechnology is implicated in medicine and agriculture to overcome the problems of agrochemicals. Chitosan nanoparticles (CS-NPs) are non-toxic and biodegradable natural polymers that used for several delivery systems, beside their anti-inflammatory and antioxidant properties. The present study aimed to explore the biochemical and molecular mechanism of CBZ-induced neural and hepatorenal toxicity in rats. Additionally, we studied the protective effect of CS-NPs against CBZ toxicity either by encapsulation or co-administration with CBZ. CS-NPs prepared by the ionic gelation method using ascorbic acid. 85 adult male Wistar rats were used in our study that divided into two experiments. In experiment (1), 60 rats were used and were divided into four groups (n=15) as follows; group (1) received normal saline and kept as control group while groups (2-4) daily received 100-, 300-, and 600 mg/kg bwt CBZ respectively via oral rout. Five rats from each group were euthanized at 7-, 14-, 28 days to collect blood and organ tissue specimen to perform several parameters. In experiment (2), 25 rats were used and divided into five groups (n=5) as follows; group (1) received normal saline and kept as control group, group (2) received CS-NPs, group (3) received CBZ, group (4) received CBZ+ CS-NPs, and group (5) received CS-loading-CBZ nanoconjugates (CS/CBZ-NCs). All rats received the treatments daily via oral rout for 28 days, then all rats were euthanized to collect blood and the same organ samples. Our results revealed that CBZ induced oxidative stress damage in the examined organs associated with neural alterations. The main lesions observed in the brain were gliosis, neuronal necrosis with chromatolysis, and neuronal edema, while liver and kidneys showed cellular degeneration and necrosis with interstitial inflammation and hemorrhage. In the brain, CBZ upregulates the m-RNA levels of NF-B, TNF-ὰ, IL-1, JNK and p53 genes, and down-regulates the MAO, AchE, and Bcl-2 genes. Liver and kidneys showed upregulation of Bax and Keap-1 genes and down-regulation of Bcl-2, Nrf-2 and HO-1 in CBZ group. Administration of CS-NPs with CBZ could improve liver and kidney biomarkers and oxidative stress values as well as improve the microscopic picture of liver and kidneys to normal histology. It also could upregulate the m-RNA levels of Nrf2 and HO-1 genes and down-regulate Keap-1 gene. Additionally, rats received CS/CBZ-NCs showed normal microscopic picture of the brain with remarkable amelioration in all studied toxicologic parameters. There was upregulation of Bcl-2 gene, and down-regulation of JNK, P53, and IL1 genes. Application of CS-NPs with CBZ either via encapsulation or co-administration could markedly reduce the neuronal and hepatorenal toxicity induced by CBZ due to their potent antioxidant, anti-inflammatory and anti-apoptotic effect.