Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol.

Abstract

Hyperlipidemia is characterized by high levels of plasma triglycerides and LDL-cholesterol, accompanied by reduced HDL-cholesterol levels, and is often associated with an increased risk of cardiovascular diseases. However, few studies have shown the effects of hyperlipidemia on genomic stability. The aim of this study was to evaluate DNA damage provided by tyloxapol induced hyperlipidemia. Tyloxapol, a non-ionic surfactant, which increases the activity of the enzyme HMG-CoA reductase and decreases clearance of lipoproteins, was used to induce hyperlipidemia in Wistar rats. Genomic instability was assessed using the comet assay which evaluates DNA strand breaks in several tissues, and the micronucleus assay in bone marrow to detect chromosomal mutagenicity for clastogenic and/or aneugenic effects. Biochemical analyses confirmed hyperlipidemia in tyloxapol-treated rats, accompanied by hyperglycemia. Higher creatinine and urea levels were observed, suggesting kidney injury. The comet assay indicated increased DNA damage in blood, liver, and kidney, but not in brain tissue. However, no increase in micronucleus frequency was observed, indicating lack of mutagenic effects. Simvastatin, used as lipid lowering drug, decreased cholesterol and triglycerides in rats treated with tyloxapol. Those findings indicate that tyloxapol-induced hyperlipidemia is able to increase genomic instability, which is associated with higher cancer risk. Therefore, this surfactant might be used in models to evaluate new hypolipidemic drugs with associated chemopreventive properties.

• Authors: Joubert Aires de Sousa, Patrícia Pereira, Mariangela da Costa Allgayer, Norma Possa Marroni, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 103 Issue 1 Pg. 51-55 (08 2017) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 28684216 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Cholesterol, HDL
• Cholesterol, LDL
• Hypolipidemic Agents
• Triglycerides
• Polyethylene Glycols
• Urea
• Creatinine
• HMG-coenzyme A reductase activator protein, rat
• Oxidoreductases
• tyloxapol

Topics

• Animals
• Brain (drug effects, metabolism)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Comet Assay
• Creatinine (blood)
• DNA Damage (drug effects)
• Genomic Instability (drug effects)
• Hyperlipidemias (blood, chemically induced)
• Hypolipidemic Agents (pharmacology)
• Kidney (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• Micronucleus Tests
• Oxidoreductases (metabolism)
• Polyethylene Glycols (toxicity)
• Rats
• Rats, Wistar
• Triglycerides (blood)
• Urea (blood)