The effect of dietary lipids on rat liver mithocondrial swelling

The swelling of liver mitochondria resulting from changes in the dietary fatty acid (FA) was investigated in rats fed two lipid diets for two or four months. Female Sprague-Dawley rats were fed two semi-synthetic and isocaloric diets. One diet (CO diet) contained 10 per cent coconut fat (rich in saturated fatty acids, SFA) while the other (SO diet) contained 10 per cent sunflower seed oil (rich in unsaturated fatty acids, UFA). The initial velocity (Vo) was used to determine the velocity of the spontaneous and phosphate - or calcium-induced sweeling of rat liver mitochondria. The changes in the fatty acid composition of the mitochondrial membranes were expressed as the unsaturation index, as well as the total content of saturated and unsaturated fatty acids and their ratios. The liver mitochondrial phospholipid fatty acid composition was very similar in both diet groups, in spite of the differences in dietary lipid fatty acid content. Only the 16:0, 16:1 (@-7) and 16:1 (@-9) fatty acids of the liver mitochondrial phospholipids differed significantly during the experiment. In general, the diets and the lenght of treatment had no significant influence on the extent of swelling. However, for animals fed the SO diet, significant differences in the for Vo of the phosphate - and calcium-induced swelling was observed. This result probably reflects greater fluidity of the mitochondrial membrane due to the high content of the fatty acid residues which would produce a more flexible and less stable membrane system

Variability and discontinuity of the pathognomonic systemic effects caused by Walker 256 tumor progression in rats.

Cancer pathognomonic systemic effects (PSE) have high individual variability. For this reason present data were collected daily and synchronized considering four main points: inoculation day, onset of PSE, aggravation and death. The subclinical period free of PSE ranged between 15.7 +/- 2.2 days, the clinical period was less variable, 8.9 +/- 0.5 days, divided in a moderate and a grave phase of nearly the same length. PSE involved disturbances of fundamental homeostatic regulations: appetite, sodium, water, immune, etc. PSE triggering correlated highly with survival (r2 = 0.95, P < 0.01), but poorly with primary tumor growth, and it was anticipated by metastases from 20.5 +/- 2.6 to 10.6 +/- 1.1 days (P < 0.01). After multifocal simultaneous inoculations, PSE triggering was anticipated to 4.2 +/- 0.2 days (marked reduction of individual variability), in the presence of small total-tumor masses, absence of macroscopic metastases, and without changes in the following clinical period features. PSE triggering seems to be a major prognostic indicator probably related to multifocal tumor growth.

Buffering of intracellular calcium in response to increased extracellular levels in mortal, immortal, and transformed human breast epithelial cells.

Extracellular levels of calcium at 1.05 mM or higher induce terminal differentiation and senescence in the mortal (MCF-10M) line of human breast epithelial cells, but does not retard the growth or induce differentiation in the immortal (MCF-10A) and oncogene transformed (MCF-10AneoT) lines. Intracellular levels of calcium and inositol triphosphate were determined in MCF-10M, MCF-10A, and MCF-10AneoT, under conditions of low and high extracellular calcium. We hereby report that increases in extracellular calcium is translated into significant increases in intracellular levels of calcium and inositol triphosphate in MCF-10M, but not in MCF-10A and MCF-10AneoT. This difference in the apparent calcium buffering capacity between the mortal and the immortalized human breast epithelial cells could account for the latter's unperturbed growth potential in high extracellular calcium environment.

The effect of thyroidectomy on male rats fed two antagonist lipid diets. IV. The fatty acid content of mitochondrial lipids of heart and gastrocnemic muscles

The fatty acid (FA) contents of heart and gatrocnemic muscle mitochondrial lipids of thyroidecromized and control (sham-operated) were analyzed. Animals were fed either an n-6 polyunsaturated (PUFA)-rich diet A or an n- PUFA-rich diet B during 30 days. It was observed alteraions in the composition of FA of those cell organelles caused by the absence of the thyroid gland. Some of these alterations were dependent of the type of used diet. Thyroidecromy caused an increase of P?S ratio in heart and gastrocnemic muscle but only for animals fed diet B. Thyroidectomy caused an increase of n-6/n-3 ratio in heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B and it caused a decrease of n-6/n-3 ratio of heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B. The absence of thyroid gland in some way may interfer in the FA metabolism and in the rate of FA incorporation into endogeneous lipids but in a different process dependent of type of tissue and of used lipid diet

The effect of the thyroidectomy in male rats fed two antagonist lipid diets. V. The mitochondrial ATPase activity of heart and gastrocnemic muscles

The mitochondrial ATPase activity of heart and gastrocnemic muscles of thyroidectomized and control rats was determined. Some rats were fed an n-6 polyunsaturated fatty acids (PUFA)-rich diet A and others were fed an n-3PUFA-rich diet B, during 30 days. The heart mitochondrial ATPase activity of rats fed diet A was higher than of rats fed diet B in both thyroidectomized (p < 0.01) and control (p < 0.05) groups. The thyroidectomy induced an increase of heart mitochondrial ATPase activity in both dietary groups (p < 0.01). The thyroidectomy also induced an increase in gastrocnemic mitochondrial ATPase activity in diet B group, but it induced a decrease in ATPase activity in diet A group. The data suggest that the dietary lipids and the absence of thyroid gland induce changes in mitochondrial ATPase activity in heart and gastrocnemic muscles, confirming the same observations previously y described for the effect of thyroidectomy and diet in rat liver and brain (9)

Effect of the thyroidectomy on male rats fed two antagonist lipid diets: I. Physiological aspects

Male rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B were subjected to a surgical thyroidectomy or to a sham-operation (control animals). Thyroidectomy caused a lesser daily increase of body weight in both dietary groups. The diet A rats showed in average greater values of body weight than diet B rats, for control and thyroidectomized animals. After 30 days of experiment thyroidectomy caused no effect on the relative weight (g/100g body weight) of liver in both dietary groups. However, it increased the relative weight) of gastrocnemius (p<0.05) and brain (p<0.001) in both dietary groups, and it decreased the relative weight of heart in both dietary groups, and it decreased the relative weight of heart in diet A (NS) and in diet B (p<0.05) groups. The relative weights of heart, gastrocnemius, liver and brain of control and thyroidectomized rats of diet A groups were lower than respective organs of diet B groups. Thyroidectomy did not affect the level of plasma proteins of diet B rats was higher than diet A rats, for controls or thyroidectomized animals. Iodine uptake by thyroid gland, the plasma level of T3 of diet B control rats were significant higher thand diet A control rats, but the plasma level of T4 of diet A control rats was higher than diet B control rats (NS). These results suggested that the thyroidectomy and or lipid diets may alter the rat development as well the ingestion of antagonist lipid diets may alter thyroid gland functions

The effect of the thyroidectomy in male rats fed two antagonist lipid diets: II. The fatty acid content of lipids of plasma and mitochondria of liver and brain

Male rats subjected to surgicl thyroidectomy showed alteration in the content of fatty acids (FA) of plasma and mitochondria of liver and brain lipids in comparison to control animals (sham-operated). Those alterations depend of the kind of dietary fat intake. Control and thyroidectomized rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B. Thyroidectomy, independently of kind of diet, did not cause any alteration on the P/S ratio in plasma or brain mithocondria. However, it caused an increase on the P/S ratio in liver mithochondria, more evident in the dietary group B. This fact may suggest that the absence of thyroid hormones would induce a higher incorporation of PUFAs in liver lipids. Thyroidectomy caused a decrease of linoleic acid (LA) content in plasma of both dietary groups but it caused an increase of LA in diet A brain mitochondria groups. The plasma FA content, although depends on the source of fat intake, was not a mere reflection of the diet FA ingested. As the thyroidectomy also changed the content of plasma FA, it is possible to postulate that the plasma FA should be actually a reflection of the FA content of endogenous lipds

The effect of thyroidectomy in male rats fed two antagonist lipid diets: III. The liver and brain mitochondrial ATPase activity

The liver and brain mitochondrial ATPase activity of surgical thyroidectomized male rats fed two antagonist lipid diets, an n06 polyunsaturated fatty (PUFA)-rich diet A or an n-3 PUFA-rich diet B, during 30 days, was different in comparison to the respective controls (sham-operated animals). Thyroidectomy did not change the diet A liver and diet B brain ATPase activity, but it increased the diet B liver ATPase (p<0.001) and decreased the diet A brain ATPase (p<0.001). The ATPase activity was also altered in function of used diets, with the exception of thyroidectomized rats in liver. The ATPase of diet A control rats was higher than the enzyme of diet B control rats in liver (p<0.001) and brain (p<0.001). The ATPase of diet A thyroidectomized rats was higher than the diet B thyroidectomized rats ATPase (p<0.005)

Possiveis alteraçoes bioquimicas causadas pela administraçao cronica de sais de litio

Sais de litio vem sendo usados ha mais de 30 anos na clinica psiquiatrica, com grande sucesso na terapia preventiva dan psicose maniaco-depressiva. Ate o presente, se desconhece o mecanismo de açao dessa droga. A dose terapeutica aproxima-se da toxica e acresce-se o fato de ser necessario o uso diario e por tempo indeterminado dos sais de litio, o que poderia causar efeitos colaterais, dos quais, na literatura, os achados de diferentes grupos de investigadores sao contraditorios. Na nossa clinica, nossas observaçoes preliminares mostram a tendencia a uma diminuiçao da funçao renal, acompanhando-se os niveis de clearance de creatinina e os niveis sericos e urinarios dos ions sodio e potassio. Por outro lado, tambem foi observada uma predisposiçao a obesidade, dependente do sexo e idade. Recentemente, iniciamos a investigaçao sobre possiveis alteraçoes no metabolismo lipidico, causadas pelo uso cronico de sais de litio, em ratos. Nossos resultados preliminares sugerem que a composiçao de acidos poliinsaturados e alterada, tanto nos tecidos encefalico e hapatico como nas hemacias. Particularmente, acidos graxos da familia do acido linoleico sofrem alteraçoes mais acentuadas.

The fatty acid composition of subcellular membranes of rat liver, heart, and brain: diet-induced modifications.

The influence of diets having different fatty acids composition on the fatty acid content of (the phospholipids) of rat liver mitochondria and microsomes, heart mitochondria, brain mitochondria and microsomes has been analyzed. It has been found that each organelle has its own peculiar composition in fatty acids. This composition may be profoundly influenced by the diet, but to different degrees in different organelles. Those of brain are most resistant. The changes observed are rather rapid, being generally already maximal after three weeks of treatment. The parallel between fatty acid composition of diets, and the changes observed in the organelles, is not strict, and is probably influenced by the metabolic competition among oleic acid, linoleic acid, linolenic acid. Unusual fatty acids like erucic acid, trans-oleic acid, and trans-linoleic acid can also become incorporated into the membranes of cell organelles.