Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC199
Prevention of oxidative stress by fructose-1,6-biphosphate in a deep hypothermia-rewarming model
J. Palomeque1, N. V. Alva1, T. Roig2, J. Bermudez2, T. Carbonell1
1. Physiology, University of Barcelona, Barcelona, Spain. 2. Physiological Sciences II, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Hypothermia induces oxidative stress in anaesthetized animals. Since fructose-1,6-biphosphate (FBP) protects against ischemia or hypoxia damage in normothermia and also it diminishes cold-induced oxidative damage at 26 oC (Gamez et al. 2008), we used a deeper hypothermia-rewarming model (21 oC) including minor surgery to study the effects of FBP on acid base balance and oxidative stress markers. Rats were anesthetized with I.P. sodium pentobarbital (60 mg/kg body weight). The carotid artery was cannulated and a catheter inserted (PE 50) for blood sampling. After tracheal intubation, respiratory aid was provided. The animals were divided into five groups: sham group sacrificed just after surgery, H (hypothermia group) cooled for 1 hour and kept in the cold for another hour, R (rewarming group) after cooling as hypothermia group rats were warmed up to 37oC. HF and RF groups corresponded to H and R treatments respectively, but pre-treated with FBP(2g/kg of body weight I.P.). All animals were sacrificed by anaesthesia overdose. Arterial blood samples were obtained to measure tissue damage indicators (transaminases, blood lactate), acid base balance (pHo, Pco2, Po2, [OH-]/[H+]) and oxidative stress indicators (lipid peroxidation, plasma thiols and erythrocyte enzymatic antioxidants). Previous studies have shown that deep hypothermia induces minor oxidative stress and metabolic acidosis (Alva et al. 2009). Rewarming is an unavoidable process after deep hypothermia treatments and provokes a more profound oxidative stress and an acute metabolic acidosis. Damage indicators increase after rewarming, but these effects are mitigated by FBP pre-treatment. Acid/base indicators and plasma thiol pool were preserved, and erythrocyte antioxidant activities were also maintained by FBP after rewarming (Table 1). Protective effects induced by FBP were evident at deep hypothermia (21 oC) in our in vivo assay. The avoidance of metabolic acidification during rewarming (Table 2) is a remarkable finding which could be responsible for the thiol pool preservation and maintaining erythrocyte antioxidant enzymatic activities in this experimental model. FBP has a clear therapeutic potential based on its ability to reduce in vivo oxidative stress damage.
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