Effect of Anticancer Quinones on Reactive Oxygen Production by Adult Rat Heart Myocytes

This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating, rat heart myocytes. Doxorubicin produced a dose-dependent increase in the rate of cyanide-resistant respiration by beating myocytes. The anthracycline analogs 4-demethoxydaunorubicin, 4 ′ -epidoxorubicin, 4 ′ -deoxydoxorubicin, and menogaril, as well as the anticancer quinones mitomycin C and menadione, also significantly increased oxygen consumption by cardiac myocytes. However, 5-iminodaunorubicin (which has a substituted quinone group) and mitoxantrone (which is not easily reduced by flavin dehydrogenases) had no effect on cardiac respiration. Both catalase (43%) and acetylated cytochrome c (19%) significantly decreased oxygen consumption that had been stimulated by doxorubicin; furthermore, extracellular hydrogen peroxide production was increased from undetectable control levels to 1.30 ± 0.02 nmol/min/107 myocytes ( n = 4 , P < 0.01 ) in the presence of 400 μM doxorubicin. These experiments suggest that the anthracycline antibiotics and other anticancer quinones stimulate cardiac oxygen radical production in intact heart myocytes; such a free radical cascade could contribute to the cardiac toxicity of these drugs.

Investigating the Response of Human Neutrophils to Hydrophilic and Hydrophobic Micro-Rough Titanium Surfaces

Various treatments have been used to change both the topography and chemistry of titanium surfaces, aiming to enhance tissue response and reduce healing times of endosseous implants. Most studies to date focused on bone healing around dental implants occurring later during the healing cascade. However, the impact of the initial inflammatory response in the surgical wound site on the success and healing time of dental implants is crucial for implant integration and success, yet it is still poorly understood. The purpose of this study was to investigate the effect of titanium surface hydrophilicity on the response of human neutrophils by monitoring oxygen radical production, which was measured as chemiluminescence activity. Materials and Methods: Neutrophils were isolated from human donors’ blood buffy coats using the double sucrose gradient method. Neutrophils were exposed to both hydrophilic and hydrophobic titanium surfaces with identical topographies in the presence and absence of human serum. This resulted in six experimental groups including two different implant surfaces, with and without exposure to human serum, and two control groups including an active control with cells alone and a passive control with no cells. Two samples from each group were fixed and analyzed by SEM. Comparisons between surface treatments for differences in chemiluminescence values were performed using analysis of variance ANOVA. Results and Conclusion: In the absence of exposure to serum, there was no significant difference noted between the reaction of neutrophils to hydrophilic and hydrophobic surfaces. However, there was a significant reduction in the mean and active chemiluminescence activity of neutrophils to serum-coated hydrophilic titanium surfaces than to serum-coated hydrophobic titanium surfaces. This suggests that surface hydrophilicity promotes enhanced adsorption of serum proteins, which leads to decreased provocation of initial immune cells and reduction of local oxygen radical production during wound healing. This can help explain the faster osseointegration demonstrated by hydrophilic titanium implants.