DRONEDARONE IS ASSOCIATED WITH ALTERATIONS IN OXIDATIVE STATUS. EXPERIMENTAL STUDY ON HYPERTENSIVE RATS

L. Pazó-Sayós1 , R. Martín-Oropesa1, P. Rodríguez-Rodríguez 3,  A. Arnalich Montiel1, MC. González 3 , B. Quintana-Villamandos 1,2,4 

1 Anestesiología y Reanimación, Hospital Gregorio Marañón, Madrid
2 Instituto de Investigación Sanitaria Gregorio Marañón, IiSGM, Madrid
3  Facultad de Medicina Universidad Autónoma de Madrid
4  Facultad de Medicina Universidad Complutense de Madrid

Background and Goal Study: Our group previously demonstrated that dronedarone has the potential to reverse the left ventricular hypertrophy (LVH) induced by arterial hypertension.1 We hypothesized that one mechanism could be a reduction in the oxidative stress. In order to prove it, we developed a global oxidative stress index (Oxy-Score) in an experimental model of arterial hypertension. 
Materials and Methods: adult male spontaneously hypertensive (SHR) rats were randomly divided into therapy group with dronedarone (SHR-D, n=9) and placebo group (SHR, n=9). Wistar Kyoto rats were used as normotensive controls (WKY, n=9). After 14 days of treatment we assessed the following plasma biomarkers of oxidative status: protein carbonyls, thiols, total antioxidant capacity, superoxide anion scavenging activity and reduced glutathione. We calculated a global score from them using the statistical methodology previously described2 (Analysis of the normality of the chosen oxidative stress biomarkers through the Kolmogorov-Smirnov test, Normalization of the parameters that did not show a normal distribution through a logarithmic transformation, Parameter standardization and Calculation of the Oxy-Score using this equation: 𝛴 antioxidants - oxidative damage). The groups were compared using single-factor analysis of variance and a post hoc Bonferroni correction was applied. All data were expressed as mean ±SEM, P< 0.05 was considered significant. All procedures were approved by the Ethics Committee of Hospital General Universitario Gregorio Marañon, Madrid, Spain.
Results and discussion: regarding individual parameters, there were no significant statistical differences among the three groups. Nevertheless, while analizing the Oxy-Score, we saw interesting differences between SHR and SHR-D group. The SHR Oxy-Score was negative, meaning a predominance of the oxidative damage. Whereas the SHR-D Oxy-Score resulted positive, indicating a predominance of the antioxidant capacity versus the oxidative damage (p<0.001). 
Conclusions: The better global antioxidant status developed by SHR treated with dronedarone could contribute to their protection in the regression of LVH.
Acknowledgements: This work was supported by a grant from FIS13/01261  PI16/02069 and Fondos FEDER, Spain. 
References:
1.	Quintana-Villamandos B, Gomez de Diego JJ, Delgado-Martos MJ, Muñoz-Valverde D, Soto-Montenegro ML, Desco M et al. Dronedarone produces early regression of myocardial remodelling in structural heart disease. PLoS One. 2017 Nov 21;12(11):e0188442. 
2.	Veglia F Cavalca V, Tremoli E. OXY-SCORE: a global index to improve evaluation of oxidative stress by combining pro- and antioxidant markers. Methods Mol Biol. 2010;594:197-213.

04 / Dronedarone associated with alterations in oxidative status. Experimental study on hypertensive rats.