Influence of endogenous prostaglandins on mTAL injury (original) (raw)
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Journal of Histology and Histopathology, 2017
Renomedullary interstitial cells (RMICs) are the most dominant cell type in inner renal medulla. Their most distinct characteristic is the presence of multiple lipid droplets in their cytoplasm. These lipid droplets are believed to be the storage units for precursors of prostaglandins (PGs), prostacyclin and medullipin. Especially prostaglandin E 2 (PGE 2) is synthesized by RMICs in kidney. PGs are produced by three key steps: 1) Arachidonic acid (AA) release from membrane phospholipids by the action of phospholipase A 2 (PLA 2); 2) Formation of prostaglandin H 2 (PGH 2) from AA by the action of cyclooxygenases (COXs); 3) Specific PG synthesis metabolism from PGH 2. PG biosynthesis can be regulated via activation or inhibition of these steps. In this study, we examined the effects of PGE 2 inhibition in different steps on RMIC function, the number of lipid droplets, medullary hyaluronan (HA) content and cell viability. We formed four groups (n=8): First group was control and treated with intraperitoneal (ip) 0.9% saline. Second group in which we inhibited AA release from membrane phospholipids was injected with ip dexamethasone (DEX) (2 mg/kg, 10 days); third group was treated with ip indomethasine (IND) (1 mg/kg, 10 days) to inhibit non-specific COX at the stage of PGH 2 formation from AA; and the fourth group was injected with ip celecoxib (CXB) (1 mg/ kg, 10 days) to examine selective cyclooxygenase-2 (COX-2) inhibition. We dissected renal medulla of the sacrificed animals after 10 days to analyze with light and electron microscopy. We counted the lipid droplets in 50 random RIMCs for each animal (x6.000 magnification) in electron microscopy. Our morphometric analysis showed that the number of lipid droplets was significantly decreased in DEX group and was significantly increased in IND and CXB groups when compared to control. In addition, medullary HA content and CD44 immunoreactivity were significantly increased in all groups when compared to control. When we analyzed cell viability, we found that RMIC apoptosis was significantly higher in PGE 2 inhibited groups when compared to control. Besides this, 24-hour urine values collected on the 10th day were significantly increased in dexamethasone and indomethacin groups; but in celecoxib group the values were similar to control. These results indicate that lipid granules may be numerical and functionally influenced from PGE 2 changes, these granules may be storage units of AA, functional changes in RMICs by PGE 2 may influence HA quantity of medullary interstitium and urine volume, and finally PGE 2 inhibition may lead to RMIC apoptosis.
2017
Prostaglandin E(1) is a natural prostaglandin that has various pharmacological effects. It has been shown that prostaglandin E(1) has a protective action on some organs of rats treated with renal ischemia/ reperfusion. Our aim was to investigate the role of prostaglandin E(1) in rats with renal ischemia- reperfusion-induced acute renal injury. Histological, immunohistochemical, and biochemical analyses were performed. Sprague Dawley male rats were divided into four groups in this study. The first group was given physiological saline only. Second group was administered prostaglandin E(1) (20 μg/kg) only. Third group was treated with ischemia-reperfusion. Fourth group was administered prostaglandin E(1) (20 μg/kg) and applied ischemia-reperfusion. All the rats were sacrificed after the reperfusion period. Dissected kidney tissue was used for histological examination and biochemical analysis. The kidneys of the experimental group with ischemia-reperfusion model have shown histopatholog...
Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat
The Journal of Nutritional Biochemistry, 1999
Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FOϩE group) or fish oil plus probucol (FOϩP group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FOϩP group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) ϩ very low density lipoprotein (VLDL) cholesterol (P Ͻ 0.05). In contrast, rats in the FOϩP group had the lowest serum total cholesterol and LDLϩVLDL cholesterol among all groups. The FO group had 26% lower kidney ␣-tocopherol concentrations than the C group. However,
Laboratory Investigation, 2019
Prostaglandin E2 receptor EP1 (PGE 2 /EP 1) promotes diabetic renal injury, and EP 1 receptor deletion improves hyperfiltration, albuminuria, and fibrosis. The role of EP 1 receptors in hypertensive kidney disease (HKD) remains controversial. We examined the contribution of EP 1 receptors to HKD. EP 1 null (EP 1 −/−) mice were bred with hypertensive TTRhRen mice (Htn) to evaluate kidney function and injury at 24 weeks. EP 1 deletion had no effect on elevation of systolic blood pressure in Htn mice (HtnEP 1 −/−) but resulted in pronounced albuminuria and reduced FITC-inulin clearance, compared with Htn or wild-type (WT) mice. Ultrastructural injury to podocytes and glomerular endothelium was prominent in HtnEP 1 −/− mice; including widened subendothelial space, subendothelial lucent zones and focal lifting of endothelium from basement membrane, with focal subendothelial cell debris. Cortex COX2 mRNA was increased by EP 1 deletion. Glomerular EP 3 mRNA was reduced by EP 1 deletion, and EP 4 by Htn and EP 1 deletion. In WT mice, PGE 2 increased chloride reabsorption via EP 1 in isolated perfused thick ascending limb (TAL), but PGE 2 or EP 1 deletion did not affect vasopressin-mediated chloride reabsorption. In WT and Htn mouse inner medullary collecting duct (IMCD), PGE 2 inhibited vasopressin-water transport, but not in EP 1 −/− or HtnEP 1 −/− mice. Overall, EP 1 mediated TAL and IMCD transport in response to PGE 2 is unaltered in Htn, and EP 1 is protective in HKD.
The Journal of Physiology, 1995
1. Modulation of the cortico-papillary electrolyte gradient by prostaglandins (PG) was studied in the kidney of anaesthetized rats. The intrarenal PG activity was varied by synthesis blockade with indomethacin (Ind) or meclophenamate (Me) and by intrarenal infusion of prostaglandin E2 (PGE2). 2. The intersttial electrolyte concentration in the medulla was continuously recorded in the kidney in situ as tissue electrical admittance (reciprocal impedance); the total renal blood flow (RBF), inulin clearance (Ci.) and renal excretion were measured simultaneously. 3. Indomethacin and Me (15 mg kg-' h-) increased tissue admittance 15-20% in the inner and 12-15% in the outer medulla (P < 0 001) whereas PGE2 (300 ng kg-' min-') decreased admittance 14 and 8%, respectively (P < 0 01). 4. Renal blood flow and Ci. were not affected by intrarenal PG activity changes. There was an increase in urine concentration after PG blockade and a delayed decrease after PGE2 infusion. 5. A joint analysis of the dynamics of medullary tissue admittance, renal haemodynamics and renal excretion provides evidence that PGs modify the medullary ionic hypertonicity by affecting NaCl transport in the ascending limb of the loop of Henle.
In vitro prostaglandin synthesis by various rat renal preparations
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1982
Prostaglandin synthesis by eight different structures from the rat kidney (whole cortex, cortical tubules, glomeruli, outer medulla, papilla, glomerular cultured epithelial and mesangial cells, cultured interstitial medullary cells) was measured in vitro after incubation with [ "C]arachidonic acid using high-performance liquid chromatography followed by RIA with four specific anti-prostaglandin antibodies (prostaglandin E,, prostaglandin F,,, 6 keto-prostaglandin F,,, thromboxane B2). Prostaglandin production by the whole cortex and cortical tubules was very low. The order of abundance for isolated glomeruli was thromboxane B, > prostaglandin E, > prostaglandin FZa ~6 keto-prostaglandin F,,. Mesangial cells synthesized prostaglandin E, at a markedly high rate, and in decreasing order: prostaglandin Fza, thromboxane B, and 6 keto-prostaglandin F,,. The same order of abundance was observed for epithelial cells. The papilla synthesized essentially prostaglandin E, and prostaglandin F,,, whereas the main product for the outer medulla was 6 keto-prostaglandin F,,. Cultured interstitial cells synthesized mainly prostaglandin E, and to a lesser extent prostaglandin F,,. Unidentified peaks eluting between 6 keto-prostaglandin F,, and thromboxane B, were also observed chiefly with glomeruli but they were absent with the medulhuy preparations. They disappeared after incubation with indomethacin or aspirin and represented for glomeruli the greatest percentage of conversion of [ 14C]arachidonic acid. These results show that the prostanoid profile varies markedly with the different regions and cells of the rat kidney.
American journal of physiology. Renal physiology, 2006
During water deprivation, prostaglandin E(2) (PGE(2)), formed by renal medullary interstitial cells (RMICs), feedback inhibits the actions of antidiuretic hormone. Interstitial PGE(2) concentrations represent the net of both PGE(2) synthesis by cyclooxygenase (COX) and PGE(2) uptake by carriers such as PGT. We used cultured RMICs to examine the effects of hyperosmolarity on both PG synthesis and PG uptake in the same RMIC. RMICs expressed endogenous PGT as assessed by mRNA and immunoblotting. RMICs rapidly took up [(3)H]PGE(2) to a level 5- to 10-fold above background and with a characteristic time-dependent "overshoot." Inhibitory constants (K(i)) for various PGs and PGT inhibitors were similar between RMICs and the cloned rat PGT. Increasing extracellular hyperosmolarity to the range of 335-485 mosM increased the net release of PGE(2) by RMICs, an effect that was concentration dependent, maximal by 24 h, reversible, and associated with increased expression of COX-2. Over...
Increased Synthesis of Prostaglandins in the Guinea Pig Following Scalding Injury
Acta Physiologica Scandinavica, 1973
HAMBEKG, M. and C.-E. JONSSON. Increased synthesis of prostaglandins in the Guinea Pig following scalding injury. Acta physiol. scand. 1973. 37. 240-245. The urinary excretion in guinea pigs of the major urinary metabolite of prostaglandins EI and E2, viz 5/3,7a-dihydroxy-ll-ketotetranor-prostanoic acid, was increased 5-9 fold following scalding injury. Lipid extracts of homogenates of scalded guinea pig skin contained 2 0 4 0 times more smooth muscle stimulating activity than did extracts of non-scalded skin. Prostaglandins (mainly PGCz and PGFz,,) were responsible for about 80 c/r of this activity.