6-ketoprostaglandin-f1-alpha and Diabetic-Nephropathies

To study the therapeutic effect of Astragalus injection (AI) in treating early stage diabetic nephropathy (DN) patients.. The total of 136 early diabetic nephropathy patients were randomly divided into two groups, 50 cases in the conventional treated group and 86 in the AI treated group, the therapeutic course being 3 weeks. Levels of plasma endothelin-1 (ET-1), 24 hrs urinary albumin excretion rate (uAER), and platelet granule membrane protein (GMP-140), 6-keto-prostaglandin F1 alpha(6-keto-PGF1 alpha), and thromboxane B2(TXB2) before and after treatment were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) respectively. Moreover, the above-mentioned criteria in 26 healthy subjects were also measured for control.. The plasma ET-1, GMP-140, TXB2 and uAER levels in DN patients were higher, but 6-keto-PGF1 alpha level was lower than those in healthy subjects. The above elevated criteria in DN patients could be lowered by AI treatment.. The pathogenesis and development of DN might be closely associated with the changes of plasma ET-1 level and platelet function. Astragalus could improve the above-mentioned changes in patients of early stage DN.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Astragalus propinquus; Diabetic Nephropathies; Drugs, Chinese Herbal; Endothelin-1; Female; Humans; Infusions, Intravenous; Male; Middle Aged; P-Selectin; Phytotherapy; Platelet Activation; Thromboxane B2

To explore the ameliorative effect and mechanism of Panax notoginseng (PNG) and ticlid in treating early diabetic nephropathy (DN).. Fifty-eight patients were divided randomly into two groups, 28 patients of the ticlid group treated with ticlid 250 mg orally, once a day and 30 patients of the PNG group treated with PNG 8 ml in 250 ml of normal saline intravenous drip once a day. The therapeutic effect and relative indexes of the two groups were observed and compared.. After treatment, in both groups, the thromboxane B2 markedly reduced and was more prominent in the ticlid group (P < 0.05), while the 6-keto-prostaglandin F1 alpha increased obviously, so as to cause a significant lowering of T/K ratio, P < 0.01. Levels of urinary albumin, beta 2 microglobulin and blood alpha 1 microglobulin of both groups were lowered significantly, P < 0.01. A significant positive linear correlation was found in the ticlid group between urinary albumin and T/K ratio (r = 0.41, P < 0.01), as well as in blood alpha 1 microglobulin with T/K ratio (r = 0.34, P < 0.05), while it was not found in the PNG group.. Ticlid and PNG were beneficial to resume the balance of T/K and improve microcirculation, reduce whole blood viscosity and decrease urinary albumin so as to retard the progress of DN.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Diabetic Nephropathies; Drugs, Chinese Herbal; Female; Ginsenosides; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Saponins; Thromboxane B2; Ticlopidine

To study the effects of Chinese herbal medicine Tangshenkang (TSK) capsule on diabetic nephropathy (DN), 57 patients with DN were randomly divided into two groups, the treated group and the control group, they were treated with TSK capsule and the conventional therapy respectively. There were serious disorders of metabolism in DN patients, that showed the TXB 2/6-keto-PGF1 alpha ratios and lipid peroxidase (LPO) levels were higher than that of healthy people. After 6 weeks treated with TSK capsule the albuminuria levels reduced obviously (decreased 51%), renal plasma flow (RPF) increased, glomerular filtration rate and the LPO levels decreased and a positive correlation was observed between albuminuria levels and TXB 2/6-keto-PGF1 alpha ratios while the clearance rate of creafinin didn't improve significantly. There were no significant difference in the above-mentioned parameters in the control group before and after treatment. These results suggested that TSK capsule possessed a significant effect in improving albuminuria and glomerular function. And the effect of TSK might be due to its adjusting TXB 2/6-keto-PGF1 alpha ratios and its lipid-peroxidation in DN patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drugs, Chinese Herbal; Female; Humans; Lipid Peroxides; Male; Middle Aged; Qi; Thromboxane B2

The effects of dietary protein on glomerular and hormonal function were studied in twelve adults with a variety of glomerular diseases. They were randomly assigned, using a crossover design, to two 11-day periods, one on a high-protein diet (2 g.kg-1.day-1) and the other on a low-protein diet (0.55 g.kg-1.day-1). Improvement in glomerular permselectivity on the low-protein diet was manifested by a decreased 24-h urinary excretion of total protein, albumin, and IgG by 33, 40, and 25%, respectively (all P less than 0.02); a fall in the fractional clearance of albumin (10.1 +/- 6.3 X 10(-3) to 5.8 +/- 3.3 X 10(-3)), and IgG (6.9 +/- 5.1 X 10(-3) to 3.5 +/- 2.3 X 10(-3)) (both P less than 0.02); and a decreased fractional clearance of neutral dextrans of molecular radii 48-56 A (P less than 0.05), when measured on the final day of each dietary period. The high-protein diet was accompanied by a higher plasma renin activity (6.9 +/- 1.6 vs. 3.5 +/- 0.8 ng angiotensin I.ml-1.h-1) (P less than 0.02), and increased excretion of prostaglandin E and 6-ketoprostaglandin F1 alpha. We conclude that a low-protein diet rapidly improves the size-selective defect in glomerular permselectivity.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aldosterone; Blood Proteins; Dextrans; Diabetic Nephropathies; Dietary Proteins; Female; Glomerulonephritis; Hemodynamics; Hormones; Humans; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Male; Metabolic Clearance Rate; Middle Aged; Prostaglandins E; Proteinuria; Renin

We used rats (the Otsuka Long-Evans Tokushima Fatty strain) as a model of type 2 diabetes to find whether thromboxane (TX) A2 is involved in diabetic nephropathy, and if so, to identify where it is synthesized. We measured urinary excretion of TXB2 and 2,3-dinor-TXB2 in rats up to 60 weeks of age as markers of renal and platelet synthesis of TXA2, respectively. Some diabetic rats were given daily oral doses of OKY-046 (100 mg/kg), a TXA2 synthase inhibitor, starting when they were 10 weeks of age. Healthy Long-Evans Tokushima Otsuka rats served as the controls. Urinary excretion of protein was greater in diabetic rats at 26 weeks than in controls, and the difference increased with age. Urinary excretion of TXB2 by diabetic rats was about 150% that of controls at 14 weeks, and remained at that level. In diabetic rats, urinary excretion of 2,3-dinor-TXB2 increased with age in parallel to increases in proteinuria, but in controls, excretion of these metabolites did not change with age. In diabetic rats, OKY-046 prevented the increase in urinary excretion of both metabolites, and decreased the proteinuria. Histologic examination at 60 weeks showed intraglomerular thrombi in diabetic rats but not in controls. OKY-046 reduced intraglomerular thrombi formation and the score for glomerulosclerosis. When platelet aggregation began, more TXA2 than before was released from the thrombi that formed, and the TXA2 contributed to the progress of nephropathy in this rat model of type 2 diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Enzyme Inhibitors; Glomerular Mesangium; Male; Methacrylates; Prostaglandins; Proteinuria; Rats; Rats, Inbred OLETF; Thrombosis; Thromboxane A2; Thromboxane-A Synthase

To study the modifying effect and mechanism of Tangshenning Recipe on micro-albuminuria in rats with early diabetic nephropathy (DN).. Male Wistar rats were randomly divided into the normal group (n=8) and model group (n=24). Intraperitoneal injecting of streptozotocin (STZ) plus complete Freund's adjuvant (CFA) was applied once a week for 3 times to induce the DN rats model. Three weeks later, the model group rats were randomly divided into pathologic group (n=8), monopril group (n=8) and Tangshenning Recipe group(n=8) according to the 24 h U-Alb. Each group's renal hemodynamics index and SOD, GSH, MDA in renal tissue were determined by radioimmunoassay (RIA) and colorimetric method respectively.. The levels of plasmatic TXB(2), the ratio of TXB(2) and 6-keto-PGF1alpha, and the CGRP in pathologic group were significantly higher than those in normal group. The levels of plasmatic ET decreased obviously, SOD decreased and MDA increased significantly in the rats' renal tissue of pathologic group. The levels of plasmatic TXB(2), the ratio of TXB(2) and 6-keto-PGF1alpha decreased significantly in both Tangshenning Recipe group and monopril group, and the therapeutic effect of Tangshenning Recipe group was better than that of monopril group. SOD was higher and MDA was lower in Tangshenning Recipe group than that in pathologic group.. The results indicates that Tangshenning Recipe can lower the micro-albuminuria in early DN rats, the mechanism of which probably lies in the modification of glycometabolism, the ratio of TXB(2) and 6-keto-PGF1alpha, the plasmatic CGRP and the renal lipid preoxidation.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Animals; Diabetic Nephropathies; Disease Models, Animal; Drugs, Chinese Herbal; Glutathione; Male; Malondialdehyde; Phytotherapy; Radioimmunoassay; Random Allocation; Rats; Rats, Wistar; Superoxide Dismutase; Thromboxane B2; Treatment Outcome

To elucidate the relationship between the thromboxane A2/prostacyclin (TXA2/PGI2) ratio and diabetic complications, the levels of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1alpha, the urinary metabolites of thromboxane A2 and prostacyclin, were measured in diabetics by gas chromatography/selected ion monitoring. We compared the TXA2/PGI2 ratio in healthy volunteers and diabetics. The TXA2/PGI2 ratio of diabetics was significantly higher than that of healthy volunteers and we could reconfirm the hypercoagulable condition in diabetics. We also investigated the difference of TXA2/PGI2 levels in diabetics with retinopathy and neuropathy. The TXA2/PGI2 ratio of diabetics with retinopathy showed significantly higher level than without retinopathy. However, the TXA2/PGI2 ratio of diabetics with neuropathy was the same as without neuropathy. These results suggest that the TXA2/PGI2 ratio reflects the pathological conditions of diabetes, especially the change of vasculature. The monitoring and improvement of TXA2/PGI2 ratio could be useful for the prevention of diabetic vascular complications.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chromatography, Gas; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Epoprostenol; Female; Humans; Male; Thromboxane B2

Rats with streptozotocin diabetes were pair-fed diets containing 20% beef tallow (BT), fish oil (FO), or safflower oil (SO) for up to six months. After one month, differences in glucose control were not observed but rats fed FO had more renal hypertrophy. FO reduced glomerular prostaglandin E2 and 6-keto F1 alpha, and BT increased thromboxane B2 production, but there were no differences in glomerular filtration rate (GFR) or renal plasma flow (RPF). Animals fed BT needed more insulin after two months than rats fed FO followed by SO. After six months, diabetic rats fed FO had larger relative kidney weights than SO or BT, but a similar pattern was present in non-diabetic controls fed the same diets. Diabetic rats fed BT had more proteinuria than diabetic rats fed SO but not FO. However, FO-fed controls had more proteinuria than controls fed SO and similar levels of proteinuria as diabetic rats fed FO. The composition of dietary fat alters glucose tolerance in diabetic rats after two months. BT increases glomerular thromboxane production and hastens proteinuria compared to SO. FO enhances renal growth and proteinuria, but this effect is independent of the diabetic condition.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Glucose; Cattle; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dietary Fats; Dinoprostone; Fats; Fish Oils; Kidney; Kidney Cortex; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Safflower Oil; Thromboxane A2

Wistar rats (4-week-old) were administered with streptozotocin (45 mg/kg) through tail veins. After 3 months, diabetic rats were divided into 2 groups. One group (EPA group, n = 16) was fed a lipid-free diet (90%, w/w) plus lard (8%) and 90% pure eicosapentaenoic acid ethyl ester (2%) for 6 months. The other group (control group, n = 16) was fed in the same way except that eicosapentaenoic acid ethyl ester was replaced by safflower oil. Twenty-four-hour urine was collected just before starting the experimental diets and during the 6-month experimental period at monthly intervals. There were no differences in food intake and body weight between the two groups throughout the experiment. The mean microalbuminuria of the EPA group became significantly lower than that of the control group after 4 months on the diets through the end of the study (6 months). The mean microalbuminuria levels at the end of the study were 1.38 mg/day in the EPA group (n = 9) and 5.19 mg/day in the control group (n = 6) (p < 0.01). Eicosapentaenoic acid administration might retard the progression of diabetic nephropathy by reducing microalbuminuria.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Eating; Eicosapentaenoic Acid; Fatty Acids; Kidney; Lipids; Male; Organ Size; Rats; Rats, Wistar; Thromboxane B2; Weight Gain

To examine the effects of endogenous thromboxane A2 on the development of diabetic nephropathy, we administered OKY-046, an inhibitor of thromboxane synthesis, to streptozotocin-induced diabetic rats. Animals were divided into three groups; nondiabetic control, diabetic, and diabetic with OKY-046, and were sacrificed 16 weeks after experimental procedures. The chronic oral administration of OKY-046 to diabetic rats significantly decreased plasma and urinary thromboxane B2 levels. Urinary protein excretion and serum glucose levels were significantly lower in the OKY-046-treated diabetic rats than in the untreated diabetics (60.8 +/- 23.2 vs. 94.1 +/- 33.4 mg/day in the 16th week, p less than 0.05 and 424.4 +/- 93.3 vs. 614.4 +/- 102.3 mg/dl in the 16th week, p less than 0.01, respectively). Platelet aggregation was inhibited by OKY-046. Blood urea nitrogen was unaffected. Ultrastructural examination revealed that the thickness of glomerular basement membrane was markedly thinner in the OKY-046-treated diabetic rats than in the untreated diabetics (197.4 +/- 29.6 vs. 288.6 +/- 46.9 nm, p less than 0.01). These results suggest that thromboxane A2 may play an important role in the development and progression of diabetic nephropathy in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Blood Glucose; Blood Pressure; Blood Urea Nitrogen; Body Weight; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Insulin; Kidney; Male; Methacrylates; Microscopy, Electron; Platelet Aggregation; Proteinuria; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Prostaglandins; Thromboxane B2

A rat model combining two-kidney, one-clip (2K1C) renovascular hypertension and streptozotocin-induced diabetes mellitus was used to assess the pathogenetic significance of vasodilator prostaglandins in diabetic glomerular injury. Glomeruli isolated from normotensive diabetic rats produced greater than normal amounts of PGE2 and 6-keto PGF1 alpha under in vitro incubation conditions. In 2K1C hypertensive-diabetic rats, glomeruli from unclipped kidneys (which are prone to accelerated diabetic glomerular injury) produced similarly elevated amounts of PGE2 and 6-keto PGF1 alpha, which significantly exceeded the levels produced by glomeruli from clipped kidneys (which are relatively protected from glomerular injury), despite exposure to a similar diabetic environment. In contrast, glomeruli from both unclipped and clipped kidneys of 2K1C hypertensive-non-diabetic rats produced normal amounts of PGE2 and 6-keto PGF1 alpha. These results suggests a correlation between vasodilator prostaglandin metabolism and susceptibility to diabetic glomerular injury, and illustrate that enhanced glomerular prostaglandin production is not an invariable metabolic consequence of hyperglycemia or insulin deficiency. The data also demonstrate that hemodynamic as well as metabolic factors may influence glomerular prostaglandin metabolism in experimental diabetes mellitus.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dinoprostone; Hypertension, Renovascular; Kidney Glomerulus; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Renal Circulation