The role of eicosanoids in cyclosporine nephrotoxicity in the rat
| Autor: | B. Chen-Gal, Joseph B. Rosenfeld, Arie Erman |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Male
medicine.medical_specialty Kidney Cortex Fractional excretion of sodium Renal cortex Renal function Cyclosporins In Vitro Techniques Kidney Biochemistry Nephrotoxicity Excretion Reference Values Internal medicine medicine Animals Blood urea nitrogen Pharmacology Kidney Medulla Chemistry Rats Inbred Strains Rats Thromboxane B2 medicine.anatomical_structure Endocrinology Prostaglandins Urine osmolality lipids (amino acids peptides and proteins) |
| Zdroj: | Biochemical Pharmacology. 38:2153-2157 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(89)90070-1 |
| Popis: | Nephrotoxicity is the most troublesome complication of cyclosporine (CSA) therapy. The present study was designed to investigate the effects of chronic treatment with CSA on the 24-hr urinary excretion of prostanoids (PGs) and thromboxane (Tx) and on the renal function in the absence or presence of indomethacin. CSA administration to Wistar rats (20 mg/kg/day, i.p.) for 14 days caused a significant increase in plasma creatinine, blood urea nitrogen (BUN), urine osmolality, fractional excretion of sodium and potassium and a reduction in creatinine clearance (CCr) and urine volume. These changes were associated with a significant reduction in urinary excretion of PGE2 (21.1 +/- 3.3 vs 33.0 +/- 2.5 ng/24 hr) and PGF2 alpha (13.4 +/- 1.4 vs 27.9 +/- 3.8 ng/24 hr) and an increase in TxB2 (12.1 +/- 3.0 vs 4.6 +/- 0.5 ng/24 hr), and 6-keto PGF1 alpha (56.2 +/- 7.7 vs 27.7 +/- 1.9 ng/24 hr). However, the synthesis of TxB2 and 6-keto PGF1 alpha by renal medullary and cortical slices prepared from CSA treated rats was not different from values obtained for vehicle treatment. In contrast, PGE2 synthesis by cortical slices prepared from the CSA group was increased. A single injection of indomethacin (10 mg/kg) to vehicle and CSA treated rats resulted in a significant reduction in PGs and TxB2 excretion. This, was associated with a further reduction in CCr (0.81 +/- 0.06 vs 1.03 +/- 0.04 ml/min) and an increase in BUN (38.5 +/- 5.2 vs 28.2 +/- 1.4 mg%) only in the CSA group. We suggest that the vasodilating PGs attenuate the renal toxic effects induced by CSA. |
| Databáze: | OpenAIRE |
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