Attenuation of ciclosporin-induced nephrotoxicity by dietary supplementation of seal oil in Sprague-Dawley rats.
Fish oil, rich in omega-3 (n-3) polyunsaturated fatty acids (PUFAs), has been reported to attenuate nephrotoxicity induced by ciclosporin (cyclosporine A). Harp seal oil is a rich source of n-3 PUFAs. This study investigated the ability of dietary seal oil to reduce nephrotoxicity caused by ciclosporin. Sprague-Dawley rats were maintained on a standard diet (with sunflower oil as lipid, SFO) or a diet enriched with seal oil (with 85% seal oil and 15% sunflower oil as lipid, SO) for four weeks before and four weeks after intravenous administration of ciclosporin (15 mg kg(-1) daily). Kidney function was assessed by measuring blood urea nitrogen, creatinine clearance, urinary N-acetyl-1-beta-D-glucosaminidase, 6-keto-prostaglandin F(1alpha), thromboxane B(2) and malondialdehyde. Systolic blood pressure (SBP) was monitored. Ciclosporin concentrations in blood were measured using liquid chromatographytandem mass spectrometry (LC-MS/MS). The fatty acid compositions of the diets and erythrocyte membranes were analysed by gas chromatography (GC). The results showed that nephrotoxicity was induced by ciclosporin in rats maintained on both SO and SFO diets. However, rats fed on SO diet endured less toxicity than those on SFO diet. The n-3 and n-6 PUFAs in the erythrocyte membrane of rats maintained on SO diet were found to be 10.79% and 11.93%, while those in rats maintained on SFO diet were found to be 1.67% and 22.71%, respectively. In conclusion, dietary supplementation of seal oil was found to reduce ciclosporin-induced nephrotoxicity in rats.
Yang
Wei
W
School of Pharmacy, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3V6.
Herzberg
Gene R
GR
Kang
Zhili
Z
Wang
Lili
L
Robb
Desmond
D
Randell
Edward
E
Smeda
John
J
Xiong
Jieying
J
Kara
Mohamedtaki
M
Liu
Hu
H
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D016572:Cyclosporine; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005227:Fatty Acids / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009821:Oils / Q000008:administration & dosage*; D010938:Plant Oils / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D046048:Seals, Earless; D000074242:Sunflower Oil; D013928:Thromboxane A2 / Q000652:urine; D013997:Time Factors
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D009821:Oils; D010938:Plant Oils; D000074242:Sunflower Oil; D008315:Malondialdehyde; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D003404:Creatinine; D000118:Acetylglucosaminidase