Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice

Autor: Gabriela Zimmermann Prado Rodrigues, Luciane Beatris Mentges Staudt, Juliana Cyrillo Guimarães da Silva, Günther Gehlen, Juliana Raquel Raasch, Juliana Machado Kayser, Taís Morgana Schoffen de Oliveira Neumann, Melina Floriano Moraes, Andriéli Carolina Schuster, Magda Susana Perassolo, Andresa Heemann Betti, Cassiana Bigolin, Eliane Dallegrave, Luciano Basso da Silva, Gabriela Schiling, Débora Graziela Farias
Rok vydání: 2020
Předmět:
Zdroj: Drug and Chemical Toxicology. 45:822-833
ISSN: 1525-6014
0148-0545
DOI: 10.1080/01480545.2020.1778018
Popis: Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects.
Databáze: OpenAIRE