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Drug Res (Stuttg) 2014; 64(6): 301-305
DOI: 10.1055/s-0033-1357196
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Crocin Improves Lipid Dysregulation in Subacute Diazinon Exposure through ERK1/2 Pathway in Rat Liver

P. Lari
1   Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
,
M. Rashedinia
1   Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
,
K. Abnous
2   Department of Medicinal Chemistry, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
,
H. Hosseinzadeh
3   Department of Pharmacodynamy and Toxicology, Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Publikationsverlauf

received 29. August 2013

accepted 23. September 2013

Publikationsdatum:
16. Oktober 2013 (online)

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Abstract

Introduction: Diazinon Yis one of the most broadly used organophosphorus insecticides in agriculture. It has been shown that exposure to diazinon may interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has been established. Earlier studies revealed the major role of Extracellular signal-regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr) expression. The aim of this study was to evaluate changes in the regulation of lipid metabolism, ERK and LDLr expression in the liver of rats exposed to subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced disturbed cholesterol homeostasis was studied.

Methods: 24 Rats were divided into 4 groups and received following treatments for 4 weeks; Corn oil (control), diazinon (15mg/kg per day, orally) and crocin (12.5 and 25mg/kg per day, intraperitoneally) in combination with diazinon (15mg/kg). The levels of cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA levels of LDLr and ERK1/2 as well as protein levels of total and activated forms of ERK1/2 in rat liver were evaluated by Western blotting and quantitative real time polymerase chain reaction analysis.

Results: Our data showed that subacute exposure to diazinon significantly increased concentrations of cholesterol, triglyceride and LDL. Moreover diazinon decreased ERK1/2 protein phosphorylation and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon-induced hyperlipemia and increased levels of LDLr transcript.

Conclusions: Crocin may be considered as a novel protective agent in diazinon-induced hyperlipemia through modulating of ERK pathway and increase of LDLr expression.

Key words

crocin - diazinon - extracellular signal-regulated kinase (ERK1/2) - hyperlipemia - LDL receptor - cholesterol
 

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