Caffeic Acid Phenethyl Ester Protects Kidney Mitochondria against Ischemia/Reperfusion Induced Injury in an In Vivo Rat Model

To improve ischemia/reperfusion tolerance, a lot of attention has been focused on natural antioxidants. Caffeic acid phenethyl ester (CAPE), an active component of the resinous exudates of the buds and young leaves of Populus nigra L., Baccharis sarothroides A., etc., and of propolis, possesses unique biological activities such as anti-inflammatory, antioxidant, immunomodulating, and cardioprotective effects, among others. There is a lack of studies showing a link between the antioxidant potential of CAPE and the mechanism of protective action of CAPE at the level of mitochondria, which produces the main energy for the basic functions of the cell. In the kidney, ischemia/reperfusion injury contributes to rapid kidney dysfunction and high mortality rates, and the search for biologically active protective compounds remains very actual. Therefore, the aim of this study was to identify the antioxidant potential of CAPE and to investigate whether CAPE can protect rat kidney mitochondria from in vivo kidney ischemia/reperfusion induced injury. We found that CAPE (1) possesses antioxidant activity (the reducing properties of CAPE are more pronounced than its antiradical properties); CAPE effectively reduces cytochrome c; (2) protects glutamate/malate oxidation and Complex I activity; (3) preserves the mitochondrial outer membrane from damage and from the release of cytochrome c; (4) inhibits reactive oxygen species (ROS) generation in the Complex II (SDH) F site; (5) diminishes ischemia/reperfusion-induced LDH release and protects from necrotic cell death; and (6) has no protective effects on succinate oxidation and on Complex II +III activity, but partially protects Complex II (SDH) from ischemia/reperfusion-induced damage. In summary, our study shows that caffeic acid phenethyl ester protects kidney mitochondrial oxidative phosphorylation and decreases ROS generation at Complex II in an in vivo ischemia/reperfusion model, and shows potential as a therapeutic agent for the development of pharmaceutical preparations against oxidative stress-related diseases.

Brief dietary protein dilution using carbohydrate rich drink protects from kidney ischemia and reperfusion injuries trough IGF-1

Objective Lifelong low-protein, high-carbohydrate diets extend lifespan in rodent. Consistently in human, the administration of oral carbohydrate drinks the day before surgery might improve clinical outcome. However, the fundamental questions of what represents a macronutritionally balanced diet, and how this impact surgical stress remain unanswered. Methods Here, we induced dietary protein dilution by giving mice ad libitum access to 50% sucrose water, without any food restriction. Mice were randomized into four regimens: regular diet (17,6 % protein, Ctrl), and a low protein diet (5.6% protein, LP), with or without high sucrose water (50% sucrose) for 7 days. At the end of the preconditioning, calorimetric data, fasting blood glucose, IGF1, glucose tolerance, and finally resistance to renal failure following a bilateral renal ischemia-reperfusion was evaluated. Results We demonstrate that access to carbohydrate drinks promotes dietary protein restriction despite a total caloric intake that was twice higher. This short-term self-restriction in daily protein, independent of caloric intake, improved insulin sensitivity, reduced serum triglyceride, and enhanced mitochondrial respiration as well as energy expenditure. Importantly, a 7-day pre-conditioning protein dilution regimen promotes recovery following kidney ischemia and reperfusion (IRI), a model of surgical stress. This protection from kidney IRI inversely correlated with pre-operative protein intake, but not carbohydrate or fat. The benefit of a low protein, high-carbohydrate regimen was independent of the protein sensing pathway eIF2α/ATF4, NRF2 and hydrogen sulfide, but instead required Insulin-like growth factor 1 (IGF1) downregulation. Conclusion These results support further clinical studies of a low protein diet combined with carbohydrate drinks prior to surgery.

Mas Receptor Blockade Promotes Renal Vascular Response to Ang II after Partial Kidney Ischemia/Reperfusion in a Two-Kidney-One-Clip Hypertensive Rats Model

Background. Partial kidney ischemia-reperfusion (IR) injury is the principal cause of acute kidney injury. The renin-angiotensin system (RAS) and hypertension also may be influenced by renal IR injury. In two models of partial renal IR with and without ischemia preconditioning (IPC) and using Mas receptor (MasR) blockade, A779 or its vehicle, the renal vascular responses to angiotensin II (Ang II) administration in two-kidney-one-clip (2K1C) hypertensive rats were determined. Methods. Thirty-seven 2K1C male Wistar rats with systolic blood pressure ≥150 mmHg were randomly divided into three groups; sham, IR, and IPC + IR. The animals in the sham group underwent surgical procedures except partial IR. The rats in the IR group underwent 45 min partial kidney ischemia, and the animals in the IPC + IR group underwent two 5 min cycles of partial kidney ischemia followed by 10 min reperfusion and partial kidney ischemia for 45 min. The renal vascular responses to graded Ang II (30, 100, 300, and 1000 ng kg−1.min−1) infusion using A779 or its vehicle were measured at constant renal perfusion pressure. Results. Four weeks after 2K1C implementation, the intravenous infusion of graded Ang II resulted in dose-related increases in mean arterial pressure (MAP) ( P dose < 0.0001) that was not different significantly between the groups. No significant differences were detected between the groups in renal blood flow (RBF) or renal vascular resistance (RVR) responses to Ang II infusion when MasR was not blocked. However, by MasR blockade, these responses were increased in IR and IPC + IR groups that were significantly different from the sham group ( P < 0.05). For example, infusion of Ang II at dose 1000 ng kg−1.min−1 resulted in decreased RBF percentage change (RBF%) from the baseline to 17.5 ± 1.9%, 39.7 ± 3.8%, and 31.0 ± 3.4% in sham, IR, and IPC + IR, respectively. Conclusion. These data revealed the important role of MasR after partial kidney IR in the responses of RBF and RVR to Ang II administration in 2K1C hypertensive rats.