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.

PEGylated meloxicam-loaded nanocapsules reverse in vitro damage on caspase activity and do not induce toxicity in cultured human lymphocytes and mice.

Meloxicam is an anti-inflammatory drug that has a potential protective effect in many common diseases. However, this molecule is quickly eliminated from the body due to it short half-life. One way to overcome this problem is to incorporate meloxicam into lipid-core nanocapsules which may increase it anti-inflammatory effects. In view of this, the objective of this work was to evaluate the potential toxicity and safety of these novel nanomaterials both in vitro and in vivo. Here, we evaluated the effects of uncoated meloxicam-loaded nanocapsules (M-NC), uncoated and not loaded with meloxicam or blank (B-NC), PEGylated meloxicam-loaded lipid-core nanocapsules (M-NCPEG), blank PEGylated lipid-core nanocapsules (B-NCPEG) and free meloxicam (M-F) in vitro through the analysis of cell viability, caspase activity assays and gene expression of perforin and granzyme B. Meanwhile, the in vivo safety was assessed using C57BL/6 mice that received nanocapsules for seven days. Thus, no change in cell viability was observed after treatments. Furthermore, M-NC, M-NCPEG and M-F groups reversed the damage caused by H2O2 on caspase-1, 3 and 8 activities. Overall, in vivo results showed a safe profile of these nanocapsules including hematological, biochemical, histological and genotoxicity analysis. In conclusion, we observed that meloxicam nanocapsules present a safe profile to use in future studies with this experimental protocol and partially reverse in vitro damage caused by H2O2.