Dietary conjugated linoleic acid renal benefits and possible toxicity vary with isomer, dose and gender in rat polycystic kidney disease.
Conjugated linoleic acid (CLA) is anti-proliferative and anti-inflammatory in the Han:SPRD-cy rat model of kidney disease. We used different doses of CLA and examined effects on renal histological benefit, the renal PPARgamma system and hepatic and renal levels of CLA isomers. Male and female offspring of Han:SPRD-cy heterozygotes were fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks before dual-energy X-ray absorptiometry, harvest of renal and hepatic tissue for histologic and lipid analysis. Both CLA diets reduced body fat content in both genders but did not change lean body mass. CLA produced a dose dependent reduction in female renal cystic change. CLA reduced fibrosis, but this reduction was significantly less with higher dose in males. CLA reduced macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. Serum creatinine rose significantly in female animals fed CLA diets. CLA treatment did not change PPARgamma activation. A significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects was identified. CLA reduces histologic renal injury in the Han:SPRD-cy rat model probably inversely proportionate to c9,t11 renal content. Possible functional CLA toxicity at high dose in female animals warrants further exploration.
Ogborn
Malcolm R
MR
Department of Pediatrics and Child Health, University of Manitoba, JBRC513-715 McDermot Avenue, Winnipeg, MB, R3C 3P4, Canada. ogborn@unbc.ca
Nitschmann
Evan
E
Goldberg
Aviva
A
Bankovic-Calic
Neda
N
Weiler
Hope A
HA
Aukema
Harold M
HM
D000818:Animals; D001823:Body Composition; D015519:Bone Density; D003404:Creatinine / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007536:Isomerism; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000737:chemistry; D008297:Male; D007690:Polycystic Kidney Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D012737:Sex Factors
D004041:Dietary Fats; D044243:Linoleic Acids, Conjugated; D003404:Creatinine