Induction of genotoxicity and differential alterations of p53 and inflammatory cytokines expression by acute oral exposure to bulk- or nano-calcium hydroxide particles in mice "Genotoxicity of normal- and nano-calcium hydroxide"

Abstract

With the high increases in the uses of calcium hydroxide in various applications due its distinctive properties, human exposure has increased to normal- and nano-calcium hydroxide. However, its impact on the DNA integrity, expression of inflammatory cytokines, and induction of oxidative stress has not been clearly studied. Therefore, here we estimate the induction of DNA damage, inflammation, and oxidative stress in mice orally administrated a single dose (100 mg/kg) of normal- or nano-sized calcium hydroxide for 24 hour. Comet, Diphenylamine and laddered DNA fragmentation assays were done to assess DNA damage induction. Acute oral administration of normal- or nano-calcium hydroxide particles disrupted the DNA integrity, caused generation of ROS and also concurrent increases in both the nitric oxide concentration and inducible nitric oxide synthase gene expression in a reverse proportional to the calcium hydroxide particles' size. Increases in the concentration of calcium ions as well as alterations in the expression level of p53 and proinflammatory cytokines were also observed in calcium hydroxide administrated groups. Moreover, administration of normal- or nano-calcium hydroxide particles suspension elevated the level of malondialdehyde and decreased both the glutathione peroxidase activity and the reduced glutathione level, as well as caused tissue injuries (e.g. renal tube degeneration, congested blood vessels, atrophied lymphoid follicles, interstitial inflammatory reaction, and hyalinosis of myocardial muscles). Thus, we conclude that calcium hydroxide acutely orally administrated in its ordinary or nano-particulate form causes DNA damage induction by generating free radicals and altering the expression levels of p53 gene and proinflammatory cytokines.