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

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.

Histopathological, genotoxic, and behavioral damages induced by manganese (II) in adult zebrafish.

Manganese is a metal often found as an environmental pollutant and very associated with neurological disorders when in high concentrations. However, little is known about the effects that this contaminant can cause when in environmentally relevant concentrations and occurrence, that is, much lower than those commonly studied. So, the aim of the study was to evaluate the effects that environmentally relevant concentrations of this metal would cause in different zebrafish organs (brain, liver, and blood). Acute 96-h and chronic 30-day exposures were performed using the manganese chloride salt as a pollutant. Behavioral alterations of anxiogenic type were observed in the animals after chronic exposures to 4.0 mg L-1 MnCl2, which traveled a greater distance at the bottom of the aquarium. This may be associated with neuronal damages in the telencephalic region responsible for motor and cognitive activity of the fish, observed in animals from the same exposure. In addition, hepatic histopathological damage as vacuolization of hepatocytes and genotoxic damage, identified by comet assay and micronucleus test, was also observed after acute and chronic exposure, especially at the highest pollutant concentrations (8.0 and 16.0 mg L-1 in acute exposure, and 4.0 mg L-1 in chronic exposure. The study reinforces the risk that environmental pollutants pose to the ecosystem, even in low concentrations.