Beneficial effects of a diet rich in a mixture of n - 6/n - 3 essential fatty acids and of their metabolites on cyclosporine - nephrotoxicity.
In this study we investigated the role of a mixture of n-6/n-3 essential fatty acids, in the cyclosporine model nephrotoxicity. Administration of cyclosporine in rats decreased creatinine clearance and provoked body weight loss, but it did not induce proteinuria and did not alter the urine volume. These changes were associated with decreased urinary ratios of prostaglandin E/thromboxane B and prostaglandin I/thromboxane B excretions. Light microscopic sections showed that 100% of the animals were affected by histological tubular lesions on their kidneys. Administration of cyclosporine to animals fed for 3 months on standard chow containing a mixture of n - 6/n - 3 essential fatty acids, restored creatinine clearance, augmented urine volume and prevented body weight loss. The improvement of renal function was accompanied by increased urinary ratios of prostaglandin E/thromboxane B and prostaglandin I/thromboxane B excretions. Light microscopic sections showed that only 40% of the animals demonstrated histological tubular lesions, of minor importance, to their kidneys. Our results suggest that the metabolites of arachidonic acid can play important role in the development of cyclosporine-nephrotoxicity because they increase the levels of thromboxane A and that the enchanced synthesis of prostaglandins (E) and (I) induced by a mixture of n - 6/n - 3 essential fatty acids, could play a beneficial role in the prevention of this renal dysfunction.
Tsipas
George
G
Laboratory of Zoology, Biochemistry and Molecular Biology. Department of Environmental and Natural Resources. Management School of Natural Resources and Enterprises Management. University of Ioannina, 301.00, Agrinio, Greece. gtsipas@cc.uoi.gr
Morphake
Polymnia
P
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015232:Dinoprostone / Q000652:urine; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D005260:Female; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D044062:Prostaglandins I / Q000652:urine; D011507:Proteinuria; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000652:urine; D015431:Weight Loss
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D044062:Prostaglandins I; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D015232:Dinoprostone