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N S Joun

Publications and source records attributed to N S Joun.

9 recordsLinked to original sources

Acute adriamycin cardiotoxicity in rats.

To explore the possible occurrence and pathogenic implications of in vivo heart lipoperoxidation in the acute model of ADR-cardiotoxicity, male Wistar rats were injected i.v. with a single dose of ADR (15 mg/kg) and the controls with saline. The rats were killed at 24 and 96 hr after treatment and at the later period the serum levels of creatine kinase of ADR-treated rats were significantly elevated. ADR-treatment did not significantly modify the cardiac concentrations of DNA, RNA, protein, the levels of activity of cardiac catalase and GSH-Px or the in vitro production of malonaldehyde of cardiac homogenates. Mitochondrial swelling at 24 hr and reduction of the mitochondrial numerical and volumetric densities along with myofilament fragmentation at 96 hr were the most significant ultrastructural changes in cardiac myocytes of ADR-treated rats. Although in vivo lipoperoxidation (diene conjugation) was detected in the cardiac lipids of only 2 out of 6 rats at 24 hr and in 3 out of 6 rats at 96 hr, no clear correlation could be found between the eventual presence of this in vivo phenomenon and any of the cardiac changes. These data suggested that lipoperoxidation may not play a fundamental role in the pathogenesis of acute ADR-cardiotoxicity in rats.

Animals↗

Influence of glucocorticoids on postnatal lung development in the rat: possible modulation by thyroid hormone.

Between the 4th and 10th days of postnatal life in the rat, serum corticosterone levels were low and basal, while the rate of [3H]thymidine incorporation into lung DNA was maximal. From day 13, serum corticosterone levels began to rise significantly, and the lung [3H]thymidine incorporation rate began to fall dramatically; however, these events were obtunded by propylthiouracil-induced hypothyroidism. When 6- to 8-day-old euthyroid pups were given a single sc injection of 10 micrograms dexamethasone, the rate of DNA synthesis in the lung fell by 96.7% of the initial rate at 24 h. This steroidal effect was blunted in hypothyroid pups and restored by exogenous thyroid hormone. The thyroid status of the pup did not modify the response patterns of lung phosphodiesterase and cytosolic glucocorticoid receptor levels to dexamethasone treatment, although both parameters were influenced by thyroid hormone availability. Radiocholine incorporation into lung phospholipids, which was altered in hypothyroidism, was unaffected by dexamethasone treatment. An in vivo assessment of radiothymidine incorporation into DNA of various tissues in 5-day-old euthyroid pups given 10 micrograms dexamethasone 24 h earlier revealed that of the several tissues in which inhibition of DNA synthesis was demonstrable, the developing lung was the most sensitive to the anti-mitogenic steroidal effect. When considered in the light of existing evidence, these observations suggest that glucocorticoids play an important role in triggering lung cytodifferentiation during the third postnatal week in the rat, and that preconditioning of the lung by thyroid hormone optimizes this developmental effect of glucocorticoids.

Aging↗

Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. III. Biochemical and morphometric parameters of the liver.

The purpose of this study was to explore in rats the possible influence of the type of dietary fat at two extreme levels of vitamin E on several biochemically determined hepatic changes and on a number of quantitatively analyzed structural and ultrastructural variations with age in hepatic cells. Six groups of weanling Wistar male rats were fed ad libitum isoenergetic diets containing similar amounts (15 g per 100 g diet) of saturated fat (coconut oil), unsaturated fat (safflower oil) or a combination of both at two levels of dl-alpha-tocopherol (2 or 200 mg per 100 g of diet). Determinations were performed in rats killed at 3, 6, 12, 18 and 24 months. Although in relation to age and irrespective of the type of diet, several of the biochemical parameters fluctuated with time, comparisons of the results between the youngest and oldest rats showed no changes in the levels of hepatic RNA, phospholipids, cholesterol, total tocopherols and total collagens, significant increases in DNA and triglycerides and a significant decrease in total protein. While the type of diet did not have in general significant influences on the levels of DNA, RNA, total protein and collagens, either the type of dietary fat and/or the levels of vitamin E had some definite effects on the levels of triglycerides, cholesterol, phospholipids and total tocopherols, as well as on the in vitro formation of malonaldehyde and on the eventual occurrence of in vivo lipoperoxidation (diene conjugation). These effects, however, varied in relation to the duration of the diverse dietary treatments. The morphologic studies indicated that all the livers had variable but generally moderate degrees of fatty changes (mainly due to triglyceride accumulation) which were attributed to the moderate obesity found in the rats. The mean nuclear and cell dimensions of hepatocytes, the number of binucleated hepatocytes, surface density of rough endoplasmic reticulum, numerical density of mitochondria and the fractional cytoplasmic volume occupied by lipofuscin pigment in hepatocytes were not significantly affected by the type of diet, by age or by the eventual occurrence of in vivo hepatic lipoperoxidation, whereas the numerical density of hepatocytes (mono- and binucleated) and "litoral cells" (endothelial, Kupffer and Ito cells), although unaffected by diet, significantly increased with age. On the other hand, the fractional volume of mitochondria and peroxisomes, as well as the numerical density of peroxisomes, were significantly influenced by the type of dietary fat and to lesser extent by the dietary levels of vitamin E.

Aging↗

Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. I. Life span, serum biochemical parameters and pathological changes.

This experiment was designed to study in rats the implications of the dietary type of fat at two levels of vitamin E on the life span as well as on several biochemical and anatomopathological age-related changes. For this purpose, six different isoenergetic diets containing 15% coconut oil (SFD), safflower oil (UFD) or a combination of both (CFD) with 2 or 200 mg% of dl-alpha-tocopherol were offered ad libitum to outbred Wistar male rats from weaning to senescence. The results indicated that up to 9--12 months the body weights of rats consuming the CFD or the UFD increased generally faster than those fed the SFD, and that all rats developed moderate degrees of obesity. Age-dependent changes in organ weights (kidneys, testes, spleen, brain, liver and heart) were unaffected by diet. Serum levels of vitamin E generally reflected the corresponding dietary levels, but were also influenced by the type of dietary fat. Serum cholesterol levels were not significantly affected by the type of diet or by age. Only transient hypotriglyceridemic and hypophospholipidemic effects of the UFD were observed and, while the levels of triglycerides decreased with age up to the 18th month followed by an increase at 24 months, the levels of serum phospholipids remained unchanged. Neither diet nor age modified the serum albumin/globulin ratios. While no differences in maximum life span were found between dietary groups, the 50% survival time of rats fed the UFD at high level of vitamin E was significantly longer than in all the other groups. This beneficial effect was related to postponement of the onset and reduction of incidence of malignant neoplasms, but was apparently not related to any particular influence on the incidence or severity of chronic nephropathy which practically developed in all rats. Various neoplastic, degenerative and inflammatory diseases encountered in rats dying during the course of the experiment were tabulated and compared with similar findings reported by others in different strains of rats. Pituitary and adrenocortical adenomas as well as adrenocortical and renal carcinomas were the most frequent tumors found in this study. All the pathological changes provided useful baseline information for the evaluation of data presented in this and subsequent communications of this series of studies.

Aging↗