Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (Danio rerio)

Aziz A. Al-Habsi, Andrey Massarsky, Thomas W. Moon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30 d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalComparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
Volume199
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Gemfibrozil
Zebrafish
Metabolism
Steroids
Cholesterol
Fish
Fishes
Hydrocortisone
Triglycerides
Pharmaceutical Preparations
Lipids
Peroxisome Proliferator-Activated Receptors
Sex Characteristics
Reproduction
Testosterone
Estradiol
Genes
Messenger RNA
Atorvastatin Calcium

Keywords

  • Fibrate drugs
  • Metabolism
  • Pharmaceuticals
  • Reproduction
  • Rhabdomyolysis
  • Statin drugs
  • Stress
  • Zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

Cite this

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abstract = "The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30 d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction.",
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