thromboxane-b2 and Kidney-Tubular-Necrosis--Acute

Topics: Adolescent; Adult; Biomarkers; Cyclic AMP; Cyclosporine; Diagnosis, Differential; Female; Graft Rejection; Hematuria; Humans; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Oliguria; Thromboxane B2

To examine the relationship between epidermal growth factor (EGF) and prostaglandins (PGs) in recovery of acute tubular necrosis (ATN) induced by gentamicin in rats and the changes of renal tissue PGs with EGF treatment.. Female wistar rats were divided into three groups; normal(NL, n = 7); GM-treated only (Group G, n = 20); GM 200 mg/kg, i.p. x 3 d; GM and EGF-treated (Group G + E, n = 19): EGF(20 micrograms) was given after last GM injection. [3H]thymidine incorporation rate (3HTdR) of renal tissue, serum creatinine concentration (Scr), renal levels of PGE2, 6-keto-PGF1 alpha, TXB2 were measured at day 1,4,8,12 after GM administration.. [3H]thymidine incorporation rate of renal tissue in group G + E was significantly higher than that in group G after toxic injury. The histological lesions of group G + E was less severe than that in group G. 6-keto-PGF1 alpha in group G + E was increased significantly than that in group G, and renal TXB2 in group G + E was lower than that in group G. PGE2 and 6-keto-PGF1 alpha in group G + E was positively correlated with 3HTdR, respectively.. (1) changes of renal prostaglandins may be related to the injury/proliferation of renal tubular epithelial cells in ATN. (2) Administration of exogenous EGF may enhance the release of PGE2 and 6-keto-PGF1 alpha of renal tissue and inhibit the synthesis of renal TXB2. The results indicate that effect of ameliorating recovery of renal tubular epithelial cells of EGF could be partly related to the changes of renal PGs.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Epidermal Growth Factor; Female; Gentamicins; Kidney; Kidney Tubular Necrosis, Acute; Rats; Rats, Wistar; Thromboxane B2

The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.01). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcium Channel Blockers; Cyclosporine; Dogs; Drug Interactions; Kidney; Kidney Tubular Necrosis, Acute; Nifedipine; Piracetam; Platelet Aggregation Inhibitors; Thromboxane A2; Thromboxane B2; Time Factors; Vasoconstriction

Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Animals; Epoprostenol; Humans; Kidney; Kidney Tubular Necrosis, Acute; Male; Rats; Renal Artery Obstruction; Superoxide Dismutase; Thiourea; Thromboxane B2; Thromboxane-A Synthase

To establish whether or not urinary excretion TxB2 is a useful parameter in the diagnosis of acute renal rejection, 45 renal transplant patients were studied and classified in four groups: Group A. Ten observations of satisfactory clinical outcome (without either acute rejection or tubular necrosis). Urinary TxB2 was initially increased but had settled to normal by the 3rd postoperative day. Two patients had subsequent increases. Group B. Twenty-five episodes of acute rejection on a previously satisfactorily functioning graft. Nineteen had increases in TxB2 values before serum creatinine increased. Group C. Five episodes of tubular necrosis without acute rejection. The evolution was similar to Group A. Group D. Nine acute episodes of rejection on kidneys with tubular necrosis. The urinary output of TxB2 was increased from the beginning. This increase was maintained until the rejection was treated. This group had the highest values of urine TxB2. The principal significance of this parameter lies in its precocity and in its utility for diagnosis of acute rejection in the graft with tubular necrosis, as the persistence of raised values of TxB2 in the urine beyond the 3rd postoperative day is highly suggestive of an acute rejection.

Topics: Acute Disease; Adolescent; Adult; Graft Rejection; Humans; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Middle Aged; Thromboxane B2

Pretreatment with the thromboxane synthase inhibitor OKY-046 but not the cyclo-oxygenase inhibitor ibuprofen protects against ischemia-induced acute tubular necrosis. However, ibuprofen together with the vasodilating agent prostaglandin E1 is protective. This suggests that a high prostaglandin to thromboxane ratio is the major factor operative in preventing tubular necrosis, the subject of this study. Rats that had unilateral nephrectomy (n = 60) with the exception of rats that had sham operations (n = 8) underwent 45 minutes of left renal pedicle clamping. Thirty minutes before the operation, the rats received either a saline solution or a thromboxane synthase inhibitor that was given intravenously. The inhibitors OKY-046 (2 milligrams per kilogram, n = 10), UK38485 (1 milligram per kilogram, n = 9) and U63357A (10 milligrams per kilogram, n = 10) were given as a single bolus while the inhibitor CGS13080 (0.1 milligram per kilogram, n = 9, and 1.0 milligram per kilogram, n = 7) was given by constant infusion and continued for 60 minutes after reperfusion. With saline solution therapy, five minutes after reperfusion, thromboxane B2 increased from 154 to 2,537 picograms per milliliter (p less than 0.00001) and 6-keto-prostaglandin F1 alpha increased from 51 to 266 picograms per milliliter (p less than 0.004). At 24 hours, the creatinine level increased from 0.5 to 2.8 milligrams per deciliter (p less than 0.00001). Only OKY-046 yielded a creatinine level at 24 hours of 1.2 milligrams per deciliter, a value lower than that for those in the saline solution control group (p less than 0.002). Furthermore, OKY-046 led to the highest prostaglandin to thromboxane ratio (p less than 0.035). The five other ratios which occurred after drug therapy were inversely related to the decrease in the creatinine value (r = -0.93, p less than 0.02). Histologically, OKY-046 was the only thromboxane synthase inhibitor to prevent acute tubular necrosis (p less than 0.05). Results show that a high prostaglandin to thromboxane ratio protects against acute tubular necrosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Benzofurans; Creatinine; Evaluation Studies as Topic; Ibuprofen; Imidazoles; Ischemia; Kidney; Kidney Tubular Necrosis, Acute; Male; Methacrylates; Pyridines; Rats; Thromboxane B2; Thromboxane-A Synthase