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The topic of sex differences in adverse responses to drugs is gaining much attention at the moment, as data in regards to gender dimorphic toxicity in the clinic are rapidly emerging [4,5]. Much of these data rule out some obvious gender differences (such as body weight and body fat) [6,7] as major causal factors. However, it is possible that hormonal signaling underlies these basic differences which are poorly understood at the moment. Hence, there is a compelling need for basic research at the molecular level, in order to comprehend and thus perhaps prevent these sex differences in adverse responses in the future. Canis familiaris, the domestic dog, is a major preclinical animal species for drug development. The species is used in a wide range of studies involving safety and efficacy, including regulatory toxicology studies and cardiovascular telemetry studies [1] and thereby in translational safety and dose-prediction models to human [2]. Therefore, in the current study, we investigate gene expression in the major drug metabolizing tissues (in addition to heart tissues) to see whether any sex differences occur - and if so - to investigate the potential implications for drug development. Another issue to consider is that apart from regulatory toxicology studies, preclinical animal studies tend to be predominantly male [3] and the concern is that sex differences, which may translate to humans in the clinic, are being overlooked. In this study we investigated gene expression profiles in dog heart tissues (ventricle and atrium), along with the major drug metabolizing tissues of the kidney (medulla and cortex), liver and small bowel (gut ileum) and used pathway analysis tools to evaluate whether major sex differences were occurring. |
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