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Bromuconazole-induced Hepatotoxicity Is Accompanied by Upregulation of PXR/CYP3A1 and Downregulation of CAR/CYP2B1 Gene Expression

Bromuconazole-induced Hepatotoxicity Is Accompanied by Upregulation of PXR/CYP3A1 and Downregulation of CAR/CYP2B1 Gene Expression

Doaa H Abdelhadya, Mohammed Abu El-Magd, Zizy I Elbialy, Ayman A Saleh

Toxicol Mech Methods. 2017 Sep;27(7):544-550.

PMID: 28532222

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 dermal route and all changes were dose dependent. This is the first investigation to report that bromuconazole-induced liver oxidative damage is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP116255482	Bromuconazol		116255-48-2	Price

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