Background and purpose: The mitochondrial permeability transition pore (mPTP), an energy‐dissipating channel activated by calcium, contributes to reperfusion damage by depolarizing the mitochondrial inner membrane potential. As mitochondrial Ca²⁺ overload is a main inductor of mPTP opening, we examined the effect of Ru₃₆₀, a selective inhibitor of the mitochondrial calcium uptake system against myocardial damage induced by reperfusion in a rat model.Experimental approach: Myocardial reperfusion injury was induced by a 5‐min occlusion of the left anterior descending coronary artery, followed by a 5‐min reperfusion in anaesthetized open‐chest rats. We measured reperfusion‐induced arrhythmias and functions indicative of unimpaired mitochondrial integrity to evaluate the effect of Ru₃₆₀ treatment.Key results: Reperfusion elicited a high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial integrity. A bolus intravenous injection of Ru₃₆₀ (15‐50 nmol kg⁻¹), given 30‐min before ischaemia, significantly improved the above mentioned variables in the ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from Ru₃₆₀‐treated ventricles was partially diminished, suggesting an interaction of this compound with the calcium uniporter.Conclusions and implications: We showed that Ru₃₆₀ treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru₃₆₀ administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mPTP. We conclude that myocardial damage could be a consequence of failure of the mitochondrial network to maintain the membrane potential at reperfusion. Hence, it is plausible that Ru₃₆₀ could be used in reperfusion therapy to prevent the occurrence of arrhythmia.British Journal of Pharmacology (2006) 149, 829–837. doi:10.1038/sj.bjp.0706932

Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX+CUR,and (4) CUR (n=8–10). Curcumin was given by gavage to NX5/6+CURand CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.