Essential fatty acid deficiency in a severely malnourished patient receiving parenteral nutrition.
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The present study was designed to examine the effects of EFA deficiency (EFAD) on biochemical, functional, and structural aspects of the kidney in growing and adult rats fed a normal or EFAD diet for 9 wk after weaning. Food and fluid intake (F1), urine volume, and Na+ and K+ excretions were measured weekly from weeks 4 to 8 by placing the rats in individual metabolic cages for 24 h. At week 9, Li+ and a 5% water load, respectively, were administered at 14 and 1.5 h prior to glomerular and proximal tubular function studies, as assessed by 3-h creatinine (C(Cr)) and Li+ (C(Li+)) clearances. Hematocrit and urine volume; serum and urine [Cr], [Li+], [Na+], and [K+]; and renal FA distribution were also measured. Data [corrected to 100 g/body weight (bw) and presented as means +/- SEM] were significant, at P< or = 0.05. Despite a similar ingestion of solids from weeks 4 to 7 (weeks 7 to 10 of life), the rats on the EFAD diet showed a decreased body weight from week 5. From weeks 4 to 8, Fl and urine volume were similar for both groups, but the Fl increased at week 6 in the EFAD group; 24-h Na+ and K+ excretions were similar at all weeks, except for an increase in the EFAD group for both ions at week 7. In the EFAD group, CCr and CLi+ decreased by 27 and 56.3%, respectively (385.7 +/- 33.4 vs. 280 +/- 21.1, and 21.0 +/- 2.1 vs. 9.2 +/- 1.1 microL/min/100 g; n = 9 vs. 10), the latter result suggesting increased proximal reabsorption. The 3-h Na+ and K+ excretions were similar, but the Li+ decreased (0.78 +/- 0.06 x 10(-2) vs. 0.32 +/- 0.03 x 10(-2) microeq/min/100 g) in the EFAD group, giving additional support to the suggestion. Renal structure was normal and similar for both groups, but the EFAD group showed a more prominent proximal tubule brush border, together with heavier periodic acid-Schiff staining in all specimens from weeks 5 to 9. In the EFAD group, FA of the n-9 and n-7 series were higher, but most of the n-6 series were lower as a percentage of total lipids in the medulla and cortex. Medullary levels of 20:4n-6 were maintained, 22:4n-6 declined twice, arachidonic acid was maintained, and 20:5n-3 was lower. The EFAD diet affected glomerular function, proximal tubular structure and function, and FA distribution in the rat kidney.
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The triacylglycerol synthesis from exogenous linoleic acid (18:2(n-6], linolenic acid (18:3(n-3], dihomogammalinolenic acid (20:3(n-6], eicosapentaenoic acid (20:5(n-3] and oleic acid (18:1(n-9] was observed to be significantly increased in isolated liver cells from female rats compared with males. The rate of fatty acid oxidation and phospholipid biosynthesis was concomitantly more important in male cells. With the C22-polyenoic fatty acids, adrenic acid (22:4(n-6] and docosahexaenoic acid (22:6(n-3), only a minor sex-related difference in fatty acid metabolism was found.
alpha-Bromopalmitate was shown to have a far more pronounced effect on metabolism of labelled linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) in isolated liver cells from female rats than in those from males. alpha-Bromopalmitate decreased triacylglycerol synthesis with a concomitant accumulation of fatty acid in diacylglycerol, indicating that the acylation of diacylglycerol is affected by alpha-bromopalmitate.
We have used a classical neurotransmitter release model to investigate the effect of dietary polyenoic fatty acids on the sensitivity of the presynaptic dopamine autoreceptor in slices of cat caudate nucleus. Maximum inhibition of [3H]dopamine release was seen only in animals fed a diet containing post delta-6-desaturation fatty acids of both the w3 and w6 series. The removal of either or both groups of fatty acids resulted in attenuation of sensitivity of the autoreceptor to apomorphine. We propose that a balance of w3 and w6 fatty acids is required to maintain normal dopaminergic function in the cat caudate nucleus.
The anticonvulsant properties of a mixture of non-esterified alpha-linolenic acid and linoleic acid with a ratio of 1:4 (SR-3) were evaluated in four rat models of epileptic seizures: (1) i.p. injection of a single convulsant dose (50 mg/kg or 100 mg/kg) of pentylenetetrazol; (2) repeated subconvulsant doses of pentylenetetrazol; (3) cortical irritation by intraventricular administration of iron chloride (FeCl3); and (4) audiogenic seizure-prone preparation created by repeated pretreatment with p-cresol. Treatment with SR-3 (about 40 mg/kg i.p.) for a period of 3 weeks prior to challenge was found effective in each of these experimental models and caused up to a 22-fold increase in latency to major motor seizures, up to 84% reduction in the number of rats with seizures, and up to a 97% reduction in the duration of seizures. It is postulated that the anticonvulsant effects of SR-3 may be related to its stabilization of neuronal membranes. SR-3 should be evaluated further as a treatment for epilepsy.