Alteration of cyclosporine (CsA)-induced nephrotoxicity by gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) in Wistar rats.
Administration of cyclosporine (CsA), 37.4 microM (45 mg)/Kg, per day for 7 days, to Wistar rats, induced decreased creatinine clearance (Ccr) and body weight loss (BWL), but it did not induce proteinuria. These changes were associated with enhanced urinary thromboxane B2 (TXB2) and diminished 6-keto-PGF1 alpha (6kPGF1 alpha) and prostaglandin E2 (PGE2) excretions. The augmentation in TXB2 and the decrease in PGs highly diminished the ratios of 6kPGF1 alpha/TXB2 and PGE2/TXB2. In microscopic sections all of the kidneys were affected to variable degrees. When CsA was administered to animals fed for 70 days, prior to the experiment, on standard chow (SC) containing evening primrose oil (EPO) or fish oil (FO), 1% and 10% respectively (EPO contained 9% gamma-linolenic acid (GLA) and FO 5.6% eicosapentaenoic acid (EPA)), the nephrotoxic effect of CsA was partially prevented. These changes were accompanied by increased ratios of urinary 6kPGF1 alpha/TXB2 and PGE2/TXB2 excretions. Light microscopic (LM) studies showed that rats' kidneys fed on SC containing EPO or FO were not always affected and the lesions were of minor importance. In conclusion, these results suggest that EPO (GLA) and FO (EPA) could play a beneficial role in the development or the modulation of the renal syndrome induced by CsA.
Morphake
P
P
Centre Franco-Hellenique de Recherche Biomedicale Hormones Vasoactives et Natriuretiques, Hopital General d'Agrinion, Hellas, Greece.
Bariety
J
J
Darlametsos
I
I
Tsipas
G
G
Gkikas
G
G
Hornysh
A
A
Papanikolaou
N
N
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015232:Dinoprostone / Q000652:urine; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005228:Fatty Acids, Essential / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008041:Linoleic Acids; D031665:Oenothera biennis; D010938:Plant Oils; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000652:urine; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D005228:Fatty Acids, Essential; D005395:Fish Oils; D008041:Linoleic Acids; D010938:Plant Oils; D011453:Prostaglandins; C028498:evening primrose oil; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D017965:gamma-Linolenic Acid; D016572:Cyclosporine; D015118:Eicosapentaenoic Acid; D003404:Creatinine; D015232:Dinoprostone