Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol
| Autor: | Joubert Aires de Sousa, Mariangela da Costa Allgayer, Norma Possa Marroni, Alexandre de Barros Falcão Ferraz, Patrícia Pereira, Jaqueline Nascimento Picada |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty DNA damage Clinical Biochemistry Hyperlipidemias 030204 cardiovascular system & hematology Biology Kidney Genomic Instability Polyethylene Glycols Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Internal medicine Hyperlipidemia medicine Animals Urea Rats Wistar Molecular Biology Tyloxapol Triglycerides Hypolipidemic Agents Micronucleus Tests Cholesterol HDL Brain nutritional and metabolic diseases Cholesterol LDL medicine.disease Rats Comet assay 030104 developmental biology medicine.anatomical_structure Endocrinology Liver Simvastatin Creatinine Micronucleus test Comet Assay Oxidoreductases Micronucleus DNA Damage medicine.drug |
| Zdroj: | Experimental and Molecular Pathology. 103:51-55 |
| ISSN: | 0014-4800 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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