[Angiotensin II of paraventricular nucleus exaggerates the renal ischemia-reperfusion injury]

Background: The renal sympathetic nerve activity [RSNA] is enhanced in renal failure. Paraventricular nucleus in hypothalamus is an important central site to regulate sympathetic activity. There are angiotensin II [Ang] II receptors in this nucleus

The aim of this study was to evaluate the effects of angiotensin II in hypothalamic paraventricular nucleus [PVN] on renal ischemia-reperfusion injury and RSNA

Methods: This study was done at 2013 in Physiology department of Tehran University of Medical Sciences. One week before the induction of renal Ischemia-Reperfusion [IR] in Sprague-Dawley rats, a cannula was inserted into the right PVN for microinjection of different doses of Ang II [3, 30, and 300 ng]

Then right nephrectomy was done. After one week recovery, renal IR injury was induced by clamping the left renal artery for 45 minute and then reperfusion for 3 or 24 hour. Ten minutes before the induction of renal ischemia-reperfusion, administration of different doses of angiotensin II were done in different groups. In all animals, left renal sympathetic activity was recorded before and during renal ischemia. After 3 or 24 hours reperfusion the blood, kidney and brain were collected to assay renal function and histology and oxidative stress indices Superoxide Dismutase, SOD and Malondialdehyde, MDA] in PVN

Results: Administration of different pharmacological doses of angiotensin II into PVN exaggerated the renal IR injury. Angiotensin II in different doses increased the plasma creatinine and BUN levels and renal histological markers in comparison to renal IR injury [P<0.05]

Angiotensin II had detrimental effects on RSNA and oxidative stress indices Super Oxide Dismutase [SOD] and Malondialdehyde [MDA] in PVN as the dose was increased [P<0.05]

Conclusion: These data showed that the PVN is a responsive site for central Ang II-induced damage in renal IR injury

We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway

[Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion- induced acute kidney injury in rats]

Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion [IR] injury. Recently, postconditioning [POC], induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney. In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation. Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats [P<0.05]. Also, POC attenuated oxidative stress in male rats' kidney tissues as demonstrated by a significantly reduced malondialdehyde [MDA] level and increased superoxide dismutase [SOD] activity [P<0.05]. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

[Recipient kidney damage after leukocyte transfer from inbred mice with renal ischemia-reperfusion injury]

In a recent study, we were able to demonstrate a role for leukocyte transfer in the induction of liver damage in recipient mice after induction of IR [60 min of bilateral renal artery occlusion and 3 hrs reperfusion] injury in donors. The present study investigates the role of leukocyte transfer in the induction of kidney damage in recipient mice after induction of renal IR injury in donors. Mice were divided into two sham and renal IR groups. After anesthesia, leukocytes were isolated from blood and were transferred to the two recipient groups: the intact recipient mice received leukocytes from the sham donor group [Sham recipient] and the intact recipient mice that received leukocytes from IR donor group [IR recipient]. After 24 hrs, the recipient mice were anesthetized and blood samples and renal tissues were collected. Renal malondialdehyde [MDA] increased and glutathione and superoxide dismutase [SOD] decreased significantly in IR recipient group in comparison to sham recipient group. Although renal function tests, including BUN and plasma creatinine were significantly different between IR donor and sham donor groups, but they were not significantly different in two recipient groups. Renal tissues in IR donor group showed extensive damage compared to sham group, but in IR recipients' kidneys, they were different from IR donor tissues despite being different from their respective sham group. These findings are suggestive of implication of leukocytes in renal tissue damage and oxidative stress after renal IR injury

[Evaluation of protective effects of postconditioning on ischemia/reperfusion-induced acute kidney injury]

In recent years, the role of reactive oxygen species [ROS] in ischemia-reperfusion injury [IRI] is established and different methods including ischemic preconditioning and postconditioning [POC] are introduced to reduce the damage. One of the possible protective mechanisms of POC is a reduction in ROS formation. According to the significance and prevalence of renal IRI, in the present study, the protective effect of POC on the reduction of IR-induced renal injury was evaluated. After right nephrectomy, male Sprague-Dawley rats were randomly assigned into three groups [n= 6]. In IR group, with the use of bulldog clamp 45 min of left renal artery was induced followed by 24 hours of reperfusion. In sham group, all of the above surgical procedures were applied except that IR was not induced. In POC group, after induction of 45 min ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. At the end of the experiments, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation. POC prevented the IR-induced increase in blood urea Nitrogen and serum creatinine and improved the kidney oxidative status demonstrated by a decrease in malondialdehyde level and an increase in superoxide dismutase. POC has a protective role on renal function by a reduction in IR-induced oxidative stress

Reduction of kidney damage by supplementation of vitamins C and E in rats with deoxycorticosterone-salt-induced hypertension

We assessed whether cosupplementation of vitamins C and E has additive beneficial effects on reducing the kidney damage and attenuation of the arterial pressure elevation compared to administration of either vitamin C or vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension. Forty rats were divided into 4 study groups and 1 sham-operated group. Unilateral nephrectomy was carried out in the study groups and hypertension was induced by deoxycorticosterone injection and 1% sodium chloride and 0.2% potassium chloride added to the drinking water. Vitamins C and E [200 mg/kg/day] or combination of them were administered with DOCA-salt for 4 weeks in 3 study groups. The effects of DOCA and salt and treatment with vitamins were compared in terms of blood pressure, urinary protein excretion, antioxidant activity of the kidneys, and renal histological changes. Four weeks of supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats had comparable significant effects in decreasing systolic blood pressure. Urinary protein excretion and histological damage did not significantly change with the combination therapy of vitamins C and E compared to the vitamin C or E alone. The renal levels of glutathione and ferric reducing/antioxidant power in combination therapy group were similar to the two other treatment groups and were significantly higher than non-treated group. Co-administration of vitamin C and E does not have an additive beneficial effect on reducing the kidney damage and hypertension compared to either vitamin C or E alone in DOCA-salt-induced hypertension

Detection of nitric oxide reduction during ischaemia - reperfusion by EPR spectroscopy

Acute renal failure is a common consequence of sepsis due to concurrent renal ischaemia. The role of nitric oxide [NO] in endotoxaemia and in ischaemic injury in the kidney is not well defined. In this study we have used an animal model of sepsis induced by injection of bacterial lipopolysaccharide [LPS] in the rat and measured renal nitric oxide by X-band electron paramagnetic resonance [EPR] spectroscopy using the spin trap Fe [2+]-N-methyl-D- glucamine dithiocarbamate [Fe[MGD]2] given by intravenous injection 6 minutes before sacrifice, The characteristic EPR spectrum of [Fe[NO][MGD]2] was observed in kidneys of rats treated with LPS for 5h. Rat kidneys subjected to 20 min ischaemia and 5 min reperfusion had lower concentrations of [Fe[NO][MGD]2] [1.0 +/- 0.6 [M] compared to the controlateral nonischaemic-kidneys [1.5 +/- 0.9 [M, P<0.05]. This study shows reduced levels of NO after renal ischaemia in vivo