Dataset Information

Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of aflatoxin B1 in rat liver.

ABSTRACT: The aims of the current study were to prepare chitosan nanoparticles (CNPs) and to evaluate its protective role alone or in combination with quercetin (Q) against AFB1-induce cytotoxicity in rats. Male Sprague-Dawley rats were divided into 12 groups and treated orally for 4 weeks as follow: the control group, the group treated with AFB1 (80 ?g/kg b.w.) in corn oil, the groups treated with low (140 mg/kg b.w.) or high (280 mg/kg b.w.) dose of CNPs, the group treated with Q (50 mg/kg b.w.), the groups treated with Q plus the low or the high dose of CNPs and the groups treated with AFB1 plus Q and/or CNPs at the two tested doses. The results also revealed that administration of AFB1 resulted in a significant increase in serum cytokines, Procollagen III, Nitric Oxide, lipid peroxidation and DNA fragmentation accompanied with a significant decrease in GPx I and Cu-Zn SOD-mRNA gene expression. Q and/or CNPs at the two tested doses overcome these effects especially in the group treated with the high dose of CNPs plus Q. It could be concluded that CNPs is a promise candidate as drug delivery enhances the protective effect of Q against the cytogenetic effects of AFB1 in high endemic areas.

SUBMITTER: Abdel-Wahhab MA

PROVIDER: S-EPMC5598511 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of aflatoxin B1 in rat liver.

Abdel-Wahhab Mosaad A MA Aljawish Abdulhadi A El-Nekeety Aziza A AA Abdel-Aiezm Sekena H SH Abdel-Kader Heba A M HAM Rihn Bertrand H BH Joubert Olivier O

Toxicology reports 20150512

The aims of the current study were to prepare chitosan nanoparticles (CNPs) and to evaluate its protective role alone or in combination with quercetin (Q) against AFB1-induce cytotoxicity in rats. Male Sprague-Dawley rats were divided into 12 groups and treated orally for 4 weeks as follow: the control group, the group treated with AFB1 (80 μg/kg b.w.) in corn oil, the groups treated with low (140 mg/kg b.w.) or high (280 mg/kg b.w.) dose of CNPs, the group treated with Q ( ...[more]

PMID: 28962409

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Project description:Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 ?g of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ? 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and ?-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced tumors. We conclude that an evaluation of gene signatures in archival tissues can be an important toxicological tool for evaluating critical molecular events associated with chemical exposures.

Dataset Information

Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of aflatoxin B1 in rat liver.

Publications

Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of aflatoxin B<sub>1</sub> in rat liver.

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