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Objective: Brain stroke is the third most important cause of death in developed countries. We studied the effect of different dietary lipids on the outcome of a permanent ischemic stroke rat model., Methods: Wistar rats were fed diets containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed) for 35 d. Stroke was induced by permanent middle cerebral artery occlusion. Coronal slices from ischemic brains and sham-operated animals were supravitally stained. Penumbra and core volumes were calculated by image digitalization after 24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were prepared from different zones and analyzed by redox status, inflammatory markers, ceramide, and arachidonate content, phospholipase A2, NOS, and proteases., Results: Soybean (S) and G diets were mainly prooxidative and proinflammatory by increasing the liberation of arachidonate and its transformation into prostaglandins. O was protective in terms of redox homeostatic balance, minor increases in lipid and protein damage, conservation of reduced glutathione, protective activation of NOS in penumbra, and net ratio of anti-to proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was less activated by O than by any other diet., Conclusion: Dietary lipids modulate NOS and PLA2 activities, ceramide production, and glutathione import into the mitochondrial matrix, finally determining the activation of the two main protease systems involved in programmed cell death. Olive oil appears to be a biological source for the isolation of protective agents that block the expansion of brain core at the expense of penumbral neurons., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The present work studies the potential restorative effect of polyunsaturated fatty acids (PUFA, 5 μM/24 h) on the dimethoate (DMT)-induced inhibition of testosterone biosynthesis in Leydig cells isolated from rat testes. Various fatty acids (FA) from the n-6 (18:2, 20:3, 20:4, 22:4 and 22:5) and n-3 (18.3, 20:5, 22:5, 22:6) series were assayed in Leydig cells, alone (as delipidated BSA complexes) and in combination with DMT (1 ppm). The n-6 FA stimulated lipid peroxidation (LPO) and inhibited the activities of steroidogenic enzymes (3β- and 17β-hydroxysteroid dehydrogenases). The n-3 FA exerted an anti-oxidant effect, decreasing the production of thiobarbituric-acid reactive substances (TBARS) and inhibiting phospholipase A(2) activity. The biosynthesis of testosterone in DMT-treated cultures was completely normalized by ARA (20:4n-6) and partially restored by the addition of 20:3n-6, increasing ARA content inside the mitochondria. The other FA assayed failed to restore androgenesis. COX-2 protein and prostaglandin F2α and E2 production were stimulated by 20:3n-6, ARA, 18:3n-3 and 20:5 n-3. COX-2 protein decreased upon addition of 22:5n-3 and 22:6n-3. StAR protein was increased by ARA and partially increased by 20:3n-6, likely due to its metabolic conversion into ARA. Both FA increased the mitochondrial cholesterol pool available for testosterone biosynthesis. The rate of androgenesis is likely the result of various regulatory factors acting concomitantly on the physiology of Leydig cells.

This work evaluates how the abnormalities in fatty acid biosynthesis, already described in diabetic rats, were extended to Sertoli and Leydig cells isolated from testes of streptozotocin-treated rats. Both kinds of cells were incubated in the presence of labeled eicosa-8,11,14-trienoic acid. The uptake of the substrate and its conversion to arachidonic acid were significantly depressed in both cell types compared to the non-diabetic controls. The indirect evidence of this inhibition was observed in the total fatty acid pattern of the cells where the 20:4 n-6/18:2 n-6 ratio was significantly decreased. The addition of insulin to the incubation medium produced no changes in the uptake of the substrate by the cells. Under similar experimental conditions the synthesis of arachidonic acid was partially recovered, however, the values obtained were still below those ones of cells isolated from control animals. These results were correlated with the fatty acid profile of different lipid fractions of plasma and with the activity of enzymes involved in polyunsaturated fatty acids biosynthesis measured in the testicular microsomes of diabetic rats. We conclude that Sertoli and Leydig cells evidenced similar lipid disorders than those observed in the whole testis or in other tissues of diabetic rats, and that the biosynthesis of arachidonic acid is under insulin regulation.

Delta 9, delta 6 and delta 5 desaturation activity and the thioesterification of eicosa-8,11,14-trienoic acid (DGLA) were measured in spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). SHR exhibited lower levels in the long-chain fatty acyl-CoA (LCFA) synthetase and in delta 6 and delta 5 desaturase activities in liver. The enzymatic activity changes were reflected on the fatty acid composition of liver microsomes. In testis, the thioesterification of DGLA and its conversion to arachidonic acid, (AA), at the delta 5 desaturation step were also depressed in SHR. We conclude that, in SHR, the alteration in polyunsaturated fatty acid (PUFA) metabolism may influence the synthesis of AA-derived eicosanoids involved in the control of blood pressure regulation.

We investigated long-chain fatty-acyl-CoA synthetase activity in rat testicular microsomes. The apparent Michaelis constants (Km's) for the substrate fatty acids increased while their corresponding maximal velocities decreased in the order 18:3(n-3), 20:3(n-6), and 18:0. The reaction with 20:3 as substrate was diminished in the presence of a constant amount of either 18:0, 18:2(n-6), or 18:3(n-3) in a manner consistent with their action as simple competitive inhibitors, with the Ki values for 18:0 and 18:3(n-3) being of the same order of magnitude as their respective Km's. Adrenocorticotrophin and/or dexamethasone administration to intact rats caused a significant decrease in the thioesterification of all three substrates without producing any alteration in the fatty-acid composition of the microsomal membranes. These results indicate the presence of a broad-specificity activating enzyme in testis whose function is subject to hormonal regulation.

The biosynthesis of arachidonic acid in Sertoli and Leydig cells isolated from the testes of mature rats has been investigated. Both types of cells incorporated [2-14C]eicosatrienoic acid from the incubation medium and transformed it into arachidonic acid. The administration of adrenocorticotropin (ACTH) to the rats decreased the delta 5 desaturating activity in the isolated testicular cells, while ACTH produced no changes in the uptake of the substrate. Similar results were obtained when ACTH was added to the incubation medium of cells isolated from non-hormone treated rats. The total fatty acid composition of the Sertoli cells isolated from ACTH-treated rats showed a significant increase in the relative percentage of 18:2n-6 and a decrease in the C20 and C22 polyenes. This may indicate that ACTH exerts an inhibitory effect on delta 6, delta 5 and delta 4 desaturase activities. Addition of corticosterone to the incubation medium also produced a significant decrease in arachidonic acid biosynthesis. Because ACTH is known to stimulate the release of corticosterone in vivo, both hormones may act cumulatively in the regulation of arachidonic acid metabolism in Sertoli and Leydig cells.