Abnormalities of Arachidonate Metabolism in Experimental Ciclosporin Nephrotoxicity

Benigni, Ariela; Perico, Norberto

doi:10.1159/000168043

Cited by 4 publications

(2 citation statements)

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“…This is the consequence of an increase in intrarenal TxA2 synthesis which has been considered one of the most important events in the pathophysiology of CS nephro toxicity [7,24], Both glomeruli [16] and macrophages [25] are implied in this increased TxA2 generation.…”

Section: Discussionmentioning

confidence: 99%

“…The acute, dose-dependent, impair ment of renal function associated with CS is mainly due to an acute change in glomerular capillary perfusion linked to an alteration in intrarenal resistances [4][5][6]. Much evidence suggests that the prostanoid system is implicated in the pathophysiology of these events: the urinary excretion of thromboxane B2 (TxB2) is increased [7], the administration of drugs achieving a selective blockade of TxA2 synthesis improves renal failure [8], vasodilating prostaglandins reduce renal damage in duced by CS [9].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

Rigotti

Amodio²,

Sacerdoti³

et al. 1991

Nephron

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Defibrotide (DF) has been proposed as a new antithrombotic agent in renal transplantation. Because it was also found to increase prostacyclin synthesis, a reduction in ciclosporin (CS) nephrotoxicity could be supposed. To ascertain this hypothesis, renal function and urinary prostanoids were evaluated in four groups of rats after 10 days of oral treatment (doses in mg/kg/day): CS 50 (group A), CS 50 + DF 400 (group B), DF 400 (group C) and controls (group D). Compared to controls, creatinine clearance (C_Cr) was significantly lower in groups A and B (In C_Cr: A = 6.62 ± 0.28, B = 6.83 ± 0.24 vs. 8.17 ± 0.13 μl/min, p < 0.01), whereas it did not change in group C (8.03 ± 0.24 μl/min). The urinary excretion of prostaglandin E₂ (PGE₂) was significantly (p < 0.05) higher in group A (In PGE₂: 3.98 ± 0.98 nmol/mol Cr) and more evidently in groups B and C (6.89 ± 0.38 and 6.01 ± 0.32 nmol/mol Cr, respectively) compared to controls (1.43 ± 0.45 nmol/mol Cr). The urinary excretion of 6-keto-PGF₁α and of thromboxane B₂ (TxB₂) were higher only in groups A and B (In 6-keto-PGF_1α and In TxB₂: A = 6.45 ± 0.22 and 4.97 ± 0.20, B = 7.06 ± 0.31 and 5.43 ± 0.41 vs. group D = 5.53 ± 0.22 and 3.79 ± 0.42 nmol/mol Cr; p < 0.05). The 6-keto-PGF_1α/Tx molar ratio was not significantly affected, although a trend for a reduction in the ratio was found in the treated rats. In conclusion, DF enhanced urinary prostanoid excretion in CS-treated rats but did not significantly affect renal function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

Rigotti

Amodio²,

Sacerdoti³

et al. 1991

Nephron

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Endocrine and metabolic abnormalities following kidney transplantation

et al. 1989

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Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance. Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed. Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phosphate metabolism. Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.

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Contribution of platelet thromboxane production to enhanced urinary excretion and glomerular production of thromboxane and to the pathogenesis of albuminuria in the streptozotocin-diabetic rat

DeRubertis

Craven

1992

Metabolism

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Abnormalities of Arachidonate Metabolism in Experimental Ciclosporin Nephrotoxicity

Cited by 4 publications

References 32 publications

Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

Endocrine and metabolic abnormalities following kidney transplantation

Contribution of platelet thromboxane production to enhanced urinary excretion and glomerular production of thromboxane and to the pathogenesis of albuminuria in the streptozotocin-diabetic rat

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