6-ketoprostaglandin-f1-alpha and Kidney-Tubular-Necrosis--Acute

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

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

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