succimer and Reperfusion-Injury

To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia.. Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups).. On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups.. The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.

Topics: Acetates; Acetylcysteine; Animals; Cyclopropanes; Kidney; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Succimer; Sulfides; Tomography, X-Ray Computed

To design and establish a model to examine whether brief periods of renal artery occlusion (ischaemic preconditioning, IP) confers protection from the effects of a subsequent period of ischaemia and reperfusion of the rat kidney.. Ninety rats were randomized into six groups, i.e. sham-operated controls; IP alone; a 20 or 40 min period of left renal ischaemia (RI) alone; and IP followed by a 20 or 40 min period of RI. Preconditioning involved the sequential clamping of the left renal artery for 4 min and its release for 11 min, a total of four times, a 'critical interval' of 30 min before the ischaemic insult. Left renal tissue integrity was determined by dimercapto-succinic acid (DMSA) radionuclide imaging on a gamma-camera both immediately (day 0) and 2 and 9 days later. Acute tubular necrosis was also assessed histologically.. RI for 20 min resulted in a significant decrease in left renal tissue integrity on day 2 only (P < 0.001), whereas RI for 40 min caused significant left renal dysfunction on day 0, day 2 and day 9 (P < or = 0.01). For a given duration of ischaemia, there was no significant difference between results from (IP + RI) rats compared with RI-only rats at any of the three times. There was no significant alteration in renal tissue integrity in the IP-only rats compared with sham-operated controls. Histological findings paralleled the data obtained from DMSA uptake.. The IP regimen and 30 min 'critical interval' confers no protection to the kidney from a 20 or 40 min ischaemic episode. The IP regimen itself appears to have no effect, confirming the validity of our experimental model.

Topics: Animals; Constriction; Disease Models, Animal; Female; Ischemic Preconditioning; Kidney; Kidney Tubular Necrosis, Acute; Organotechnetium Compounds; Radiography; Radionuclide Imaging; Rats; Rats, Wistar; Renal Artery; Reperfusion Injury; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase. Previous work has indicated that methylene blue accepts electrons from xanthine oxidase at the iron-sulfur center. Initial experiments in our laboratory demonstrated that (1) pairs of electrons from each enzymatic oxidation are transferred to methylene blue, (2) the reduction of methylene blue can be achieved by model iron-sulfur centers, similar to the iron-sulfur center of xanthine oxidase, (3) reduced methylene blue auto-oxidizes to produce H2O2 directly, rather than O2-, and (4) methylene blue is effective at non-toxic levels (2-5 mg/kg) in preventing free radical damage to liver and kidney tissues in an in vitro model of ischemia and reoxygenation. Accordingly, we propose that methylene blue may represent a new class of antioxidant drugs that competitively inhibit reduction of molecular oxygen to superoxide by acting as alternative electron acceptors for tissue oxidases. We have termed these agents "parasitic" electron acceptors.

Topics: Animals; Antioxidants; Hypoxanthine; Hypoxanthines; In Vitro Techniques; Kidney; Lipid Peroxidation; Liver; Methylene Blue; Models, Biological; Oxidation-Reduction; Rats; Reperfusion Injury; Succimer; Superoxides; Xanthine; Xanthine Oxidase; Xanthines