Bromuconazole-induced hepatotoxicity is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1 gene expression

Toxicology Mechanisms and Methods
Doaa H AbdelhadyaAyman A Saleh

Abstract

Despite widespread use of bromuconazole as a pesticide for food crops and fruits, limited studies have been done to evaluate its toxic effects. Here, we evaluated the hepatotoxic effect of bromuconazole using classical toxicological (biochemical analysis and histopathological examination) and gene-based molecular methods. Male rats were treated either orally or topically with bromuconazole at doses equal to no observed adverse effect level (NOAEL) and 1/10 LD50 for 90 d. Bromuconazole increased activities of liver enzymes (ALT, AST, ALP, and ACP), and levels of bilirubin. It also induced hepatic oxidative stress as evidenced by significant decrease in the activities of superoxide dismutase (SOD), and significant increase in levels of malondialdehyde (MDA) in liver. In addition, bromuconazole caused an increase in liver weights and necrobiotic changes (vacuolation and hepatocellular hypertrophy). It also strongly induced the expression of PXR and its downstream target CYP3A1 gene as well as the activity of CYP3A1. However, it inhibited the expression of CAR and its downstream target CYP2B1 gene without significant changing in CYP2B1 activity. Overall, the oral route showed higher hepatotoxic effect and molecular changes than the...Continue Reading

References

Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
May 22, 2003·Journal of Pediatric Hematology/oncology·Kelly L VanierDonna L Johnston
Mar 18, 2006·Toxicology and Applied Pharmacology·Daland R JubergAndrew Parkinson
Apr 29, 2006·Toxicology and Applied Pharmacology·Douglas B TullyDavid J Dix
May 30, 2006·Toxicology and Applied Pharmacology·Amber K GoetzDavid J Dix
Jun 20, 2006·Reproductive Toxicology·Elena MenegolaErminio Giavini
Jun 15, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard C PefferIvan Rusyn
Jun 19, 2007·Journal of Toxicology and Environmental Health. Part a·Christopher S MazurJohn C Lipscomb
Apr 14, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stephen NesnowSusan D Hester
May 5, 2009·Toxicology and Applied Pharmacology·Amber K Goetz, David J Dix
May 9, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amber K Goetz, David J Dix
Aug 29, 2009·Journal of Proteome Research·Maribel BrunoYue Ge
Mar 30, 2010·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·S G Edwards, N P Godley
Feb 16, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Susan HesterStephen Nesnow
Sep 4, 2014·Archives of Toxicology·T HeiseP Marx-Stoelting
Dec 30, 2014·Cytotherapy·Somia H Abd-AllahMohammed Abu El-Magd
Jan 23, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mohamed Abdel-DaimAhmed M Hassan

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Citations

May 28, 2019·Current Environmental Health Reports·Banrida WahlangMatthew C Cave
Jun 6, 2020·Expert Opinion on Drug Metabolism & Toxicology·Jingheng WangTaosheng Chen
Oct 6, 2018·Environmental Science and Pollution Research International·Mohammed El-AdawyMohammed Abu El-Magd
Oct 8, 2018·Environmental Science and Pollution Research International·Mai M ElkeiyMohammed A El-Magd
May 21, 2021·Ecotoxicology and Environmental Safety·Tingting KuNan Sang
Mar 30, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mohammed A El-MagdMohamed A Basyony

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