The Effect of Indomethacin and Prostaglandin (PGE2) on Renal Failure Due to Glycerol in Saline-Loaded Rats

Papanicolaou, N.; Callard, P; Bariéty, J; Milliez, P

doi:10.1042/cs0490507

Cited by 20 publications

(13 citation statements)

References 16 publications

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“…When the platelets aggregate (by the increased TXA2 and the diminished PGE2 and 6kPGF)a production by CsA) (table 2) and liberate their contents, the released 5-HT together with TXB2 (TXA2) contract the afferent arterioles resulting in decreased renal blood flow (RBF) and GFR, strongly implicated in the pathogenesis of CsA-induced nephrotoxicity [4,11,13]. Furthermore, chronic CsA administration was associated with irreversible structural changes [6] and/or hemolytic uremic syndrome [26].…”

Section: Effect O F Csa In Kts-pretreated Ratsmentioning

confidence: 99%

“…In previous studies it has been found that infusion of PGs [13][14][15][16] or inhibition ofTXA2 synthesis [10][11][12] pro tected against the development of ARF. Because CsA enhanced TXB2 (TXA2) and diminished PGs, we ex pected the NT induced by this agent to be more serious than that induced by substances such as glycerol (GRL) [10,11], mercuric chloride (MC) [24] and gentamicin (GM) [12] which were found to enhance both TXA2 and PG production.…”

Section: Effect O F Csa In Normal Ratsmentioning

confidence: 99%

“…For example, TXB2 is a potent vasoconstrictor [27,28] and platelet aggregator agonist [29]. Platelet aggregation is also implicated in glomerular injury [30][31][32][33], TXA2 is also a leukocyte chemoattractant; therefore, the well-known tissue-damaging effects of stim ulated leukocytes could come into play [34,35], The decreased PG production (PGE2, PGH) by CsA facili tated the role of TXA2 and 5-HT, because PG infusion has previously been shown to reduce immune complex autoimmune glomerulonephritis [36][37][38][39] and ARF [13][14][15][16]24], Thus, KTS that was found to increase the ratios of PGE2/TXB2 and 6kPGE|a (PGI2)/TXB2 (table 3) and, furthermore, antagonizes the vasoconstrictor S2 seroton ergic receptors [9], prevents the NT induced by CsA. In conclusion, KTS by antagonizing the vasoconstrictor S2 (mainly) serotonergic, a 1 adrenergic and Hi histaminergic receptors, without affecting the vasodilator S2 serotoner gic receptors [9,25] and by increasing the ratios of PGE2/ TXB2 and 6kPGF|"/TXB2 prevented, at least in part, the NT induced by CsA.…”

Section: Effect O F Csa In Kts-pretreated Ratsmentioning

confidence: 99%

“…This agent also antagonizes the amplifying effects of 5-HT on other vasoconstrictor substances, such as catecholamines (ai adrenergic receptors), histamine (H2 histaminergic receptors) and PGF2o [9], Since it has been observed in previous studies that the metabolites of arachidonic acid play an important role in development, thromboxane (TXA2) [10][11][12], or in protec tion, prostaglandins (PGE!, PGE2, PGI2) [13][14][15][16], against acute renal failure (ARF), in our studies we also examined the role of these agents.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Darlametsos¹,

Morphake²,

Bariéty

et al. 1995

Nephron

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Cyclosporine (CsA)-treated female Wistar rats, in dose of 37.5 μM (45 mg)/ kg/day for 7 days, exhibited significantly decreased creatinine clearance (Ccr), and provoked body weight loss (BWL), which is consistent with the development of nephrotoxicity (NT). Urine volume (V) did not change and proteinuria (PU) was not provoked. These changes were associated with significantly diminished ratios of urinary PGE₂/TXB₂ and 6kPGF_1α/TXB₂ excretions. Light-microscopic (LM) sections of rat kidneys showed that all kidneys were affected but the lesions (mainly diffuse vacuolization) were reversible. When CsA-treated animals were pretreated with ketanserine (KTS), which antagonizes (a) the direct vasoconstrictor effect of serotonin (5-HT), and (b) the amplifying effects of 5-HT on other vasoactive substances (such as noradrenaline (NA), α₁-receptors, histamine, H₂ receptors, and prostaglandin F_2α), Ccr and urine volume significantly increased, BWL was partially prevented and the ratios of urinary PGE₂/TXB₂ and 6kPGF_1α/TXB₂ excretions were significantly enhanced. LM sections showed that only 5 of 9 rats were affected but the lesions were of less importance. These observations indicate that the NT induced by CsA in our studies was mediated by 5-HT, a potent vasoconstrictor agent, and by the metabolites of arachidonic acid. However, other vasoactive agents and additional mechanisms could also be implicated.

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Section: Effect O F Csa In Kts-pretreated Ratsmentioning

confidence: 99%

Section: Effect O F Csa In Normal Ratsmentioning

confidence: 99%

Section: Effect O F Csa In Kts-pretreated Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Darlametsos¹,

Morphake²,

Bariéty

et al. 1995

Nephron

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“…This property of prostaglandins has been termed cytoprotection (Chaudhury & Jacobson, 1978), although more properly it should be described as organoprotection (Szabo & Szelenyi, 1987). It is now known that the cytoprotective effects of prostaglandins extend to tissues other than the stomach, including the heart (Lefer et al, 1978;Ferrari et al, 1989), pancreas (Manabe & Steer, 1980), kidney (Papanicolaou et al, 1975;Ruwart et al, 1981) and liver (Stachura et al, 1980). It is likely that in many of these tissues cytoprotection is by a different, or additional mechanism, from that which operates in the stomach.…”

Section: Introductionmentioning

confidence: 99%

Cytoprotection by iloprost against paracetamol‐induced toxicity in hamster isolated hepatocytes

Nasseri-Sina

Fawthrop

Wilson

et al. 1992

British J Pharmacology

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The ability of iloprost (ZK36374) to protect hamster isolated hepatocytes from the toxic effects of paracetamol and its reactive metabolite N‐acetyl‐p‐benzoquinoneimine (NABQI) was investigated. The cytoprotection provided by iloprost was compared with that of N‐acetyl‐l‐cysteine. Treatment of hepatocytes with either NABQI (0.4 mm) or paracetamol (2 mm) alone resulted in a considerable loss of cell viability, as assessed by trypan blue exclusion or leakage of lactate dehydrogenase, accompanied by an increase in the percentage of viable cells that were blebbed. N‐acetyl‐l‐cysteine (1.25 mm) pretreatment diminished the loss of cell viability and the percentage of blebbed cells resulting from exposure to NABQI or paracetamol, whereas iloprost (10−16 m to 10−10 m) pretreatment reduced only the loss of cell viability, not the percentage of viable cells exhibiting blebbing. Pretreatment with N‐acetyl‐l‐cysteine significantly attenuated the depletion by paracetamol of glutathione and decreased the covalent binding of [14C]‐paracetamol to cellular proteins, whereas iloprost was without any such effects. The effects of iloprost and N‐acetyl‐l‐cysteine were also investigated by use of a model of paracetamol toxicity in which it is possible to study the biochemical events leading to cell injury separate from the generation of toxic metabolites. Hamster hepatocytes were incubated with paracetamol (4 mm) for 90 min at 37°C during which metabolism of paracetamol occurs with minimal loss of cell viability. Following washing of cells, to remove paracetamol and its metabolites, there was a progressive loss of viability and increase in the percentage of cells exhibiting blebbing when incubated in buffer alone. Addition of either N‐acetyl‐l‐cysteine (1.25 mm) or iloprost (10−14 m to 10−8 m), following washing, significantly reduced the expected loss of cell viability. Iloprost at concentrations outside this range was without effect. Paracetamol toxicity to isolated hepatocytes could be prevented or delayed by treatment with either N‐acetyl‐l‐cysteine or iloprost, but whereas the former prevented or even reversed plasma membrane blebbing with a resultant reduction in the percentage of viable cells that were blebbed, the prostanoid appeared only to delay the progression from plasma membrane blebbing to loss of viability. Hence, the percentage of viable cells that were ultimately blebbed following exposure to paracetamol was not significantly reduced by addition of iloprost. Aspirin or ibuprofen exacerbated the loss of viability induced by prior incubation with paracetamol. Thus, there may be a role for endogenous prostaglandins in protecting hepatocytes from paracetamol toxicity. Iloprost is cytoprotective without any effect upon toxin metabolism or detoxication. The mechanism of action of iloprost probably does not involve induction of prostaglandin synthesis or activation of the previously‐characterized prostacyclin receptor.

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The early phase of experimental acute renal failure

et al. 1979

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Experiments were conducted to determine whether suppression of the renin-angiotensin-system and inhibition of the tubuloglomerular feedback response offer protection from acute renal failure, as found in chronically-salt loaded animals. The juxtaglomerular renin activity and tubuloglomerular feedback response were inhibited acutely, by saline expansion, or chronically, by DOCA-treatment with saline drinking fluid or salt diet, by high salt diet alone, or by inducing two-kidney Goldblatt hypertension. The chronic pretreatment procedures depressed juxtaglomerular renin to 16, 7, 13 and 4% of control, respectively, inhibited the feedback response to 53, 37, 56, and 38% of control, respectively, but conferred no benefit in the first hours following a nephrotoxin or ischaemia. In contrast, the acute treatment procedure reduced juxtaglomerular renin activity to only 56% and lowered the feedback response to only 71%, but improved renal function after the nephrotoxin, although not after ischaemia. It is concluded that since severe restrictions of renin activity and tubuloglomerular feedback are not protective, neither is primarily involved in generating the functional restrictions early in acute renal failure. The restoration of renal function by saline expansion accompanied only a modest depression of these two systems and suggests that the beneficial effect may result more from volume expansion or diuresis than from suppression of renal renin or inhibition of tubuloglomerular feedback.

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The Effect of Indomethacin and Prostaglandin (PGE2) on Renal Failure Due to Glycerol in Saline-Loaded Rats

Cited by 20 publications

References 16 publications

Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Cytoprotection by iloprost against paracetamol‐induced toxicity in hamster isolated hepatocytes

The early phase of experimental acute renal failure

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