The effect of pantothenic acid (PA) deficiency on the adrenocortical function was investigated in young male rats fed a PA-deficient (PAD) diet over a period of about three months. Pair-weight (PW) and ad libitum (AL) fed rats served as controls. Basal 08.00h (lights on) plasma levels of corticosterone were regularly found to be reduced in PAD and AL rats compared with those in PW animals. Investigation of the circadian rhythm of plasma corticosterone revealed that the elevated 08.00h hormone concentrations of PW rats are due to a biphasic 24-h pattern of plasma corticosterone with a distinct glucocorticoid peak at lights on and another one at lights off (20.00h), whereas PAD and AL rats only show one clear increase in plasma corticosterone levels at the beginning of the dark period. However, the evening glucocorticoid peak of the PAD rats was markedly higher than that of the PW and AL groups. Thus an adrenocortical overactivity is ascertained in PA deficiency which is presumably responsible for the adrenal hypertrophy generally observed in earlier studies on PA depletion in rats. Multiple examinations of the secretory capacity for corticosterone, each carried out half an hour after i.m. administration of 2.5 IU ACTH1-24, revealed comparable plasma responses to supraphysiological ACTH stimulation in PAD, PW, and AL rats. Therefore we concluded that corticosterone secretion is not impaired in PA deficiency, at least not that elicited for short periods by adrenocortical overstimulation. Additional measurements of the adrenal cholesterol content and the circadian plasma levels of dehydroepiandrosterone-sulphate were carried out in all three diet groups. The respective results are discussed with regard to the stress situation produced by the experimental PA deficiency.
Basal as well as human chorionic gonadotropin (hCG)-stimulated plasma levels of testosterone were investigated in rats after different periods on a pantothenic acid (PA)-deficient diet. No clear effects of PA deficiency on circulating testosterone concentration were discernible when blood samples of resting (untreated) animals were examined. However, following long-term stimulation with hCG (100IU hCG/day, administered i.m. on 4 consecutive days) the secretory capacity for testosterone as reflected by the plasma androgen responses was found to be markedly reduced in PA-deficient compared with pair-weight fed control rats. Additional measurements of cholesterol in high density lipoproteins revealed that this primary source of precursors for steroid hormone synthesis in the rat is unaffected following a PA depletion. These results are discussed with respect to lowered tissue levels of coenzyme A on the one hand and testicular degeneration on the other hand, both occurring regularly in an advanced PA deficiency stage.
In view of the antioxidant properties of ascorbic acid (AA), effects of inadequate and excessive doses of AA on hepatic and pulmonary antioxidant enzymes and NADPH-dependent lipid peroxidation were investigated in the present study. Male guinea pigs, dosed daily with 0.2mg AA/100g b wt (inadequate) or 50mg AA/100g b wt (excessive) for 8 weeks, demonstrated no difference in body growth, liver and lung weights, and post-10, 000×g supernatant protein contents as compared with the control group, which was daily fed with 2mg AA/ 100g b wt. Inadequacy of AA decreased the hepatic and pulmonary contents of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), but it significantly increased glutathione reductase (GR) activity (p<0.005) in lung. However, levels of hepatic and pulmonary NADPH-dependent lipid peroxidation remained unaltered when the supply of AA was inadequate. Excessive doses of AA did not influence any pulmonary antioxidant enzyme, level of NADPH-dependent lipid peroxidation and content of reduced glutathione (GSH), but increased the hepatic GSH-Px and GR activities. Hepatic SOD activity showed a significant decrease (p<0.01), whereas NADPH-dependent lipid peroxidation and GSH contents remained unchanged. It appears that the changes in antioxidant enzymes may be a nonspecific response to AA or these changes may not be sufficient to bring about any shift in the levels of NADPH-dependent lipid peroxidation in the presence of unaltered GSH contents or other biomolecules which may act as antioxidants or free radical scavengers in the cell system.
The present study aimed to investigate various biochemical constituents in serum of male guinea pigs of differing serum prolactin status. Four similar groups of apparently healthy male guinea pigs were used in this study. The first group was used as the control; the second group was made hyperprolactinemic with daily doses of 1mg estrogen; the third group was made hypoprolactinemic with daily doses of 2.5mg bromocriptine; the fourth group, after being similarly dosed with estrogen, was again orally dosed with bromocriptine. Results revealed that estrogen induced a marked serum hyperprolactinemia accompanied with a significant rise in serum levels of estradiol-17β, insulin, and calcium; while serum levels of glucose, magnesium, and inorganic phosphorous were found to be significantly decreased. These serum constituent levels approached to almost their control levels after bromocriptine administration. Bromocriptine without estrogen promoted a marked decrease in serum prolactin and estradiol-17β, but other serum parameter levels remained almost within their normal range. The biochemical changes detected in the present study may be useful in clinical diagnosis and treatment of prolactinemia.
To study the effect of increased copper levels on erythrocyte lipid peroxidation, we fed a diet containing 2g Cu/kg diet fed to normal and bile-duct ligated rats. No significant change was observed either in endogenous lipid peroxide content or in stimulated lipid peroxidation in the erythrocytes of rats with increased copper levels compared with the levels in control groups.
When young male Wistar rats were fed a diet containing a minute amount of riboflavin, the blood level of each of flavin adenine dinucleotide, flavin mononucleotide, and riboflavin was decreased after 1 week of feeding and remained low after 2 and 3 weeks of feeding. Glutathione reductase activities in the liver and erythrocytes were decreased after 2 weeks of feeding. Then, a significant increase in serum lipid peroxide level was observed one week later. In accordance with the increase in serum lipid peroxides, incipient electron microscopic changes occurred in the lenses of the rats, i.e., swelling of mitochondria in the epithelial cells and the appearance of vacuoles in the fibers. The vacuoles became larger after 6 weeks of feeding on the diet. The administration of linoleic acid hydroperoxide to rats fed the diet containing a minute amount of riboflavin brought about a further increase in serum lipid peroxide level, and the number of vacuoles formed in the lens fibers was increased and their size became larger. These findings support the view that lipid peroxides increased in the blood are the cause of cataractogenesis.
To compare the hypocholesterolemic effect and other biological activities of 2-methoxyestriol (2-MeOE3) and estradiol-17β (E2-17β), osmotic minipumps (transporting rate at 37°C, 0.5μl propylene glycol/h) containing these hormone solutions at either of 2 concentrations, 3mg/ml (36μg/day administration, “low dose”) and 30mg/ml (360μg/day administration, “high dose”) were implanted subcutaneously into previously oophorectomized female rats which were fed a diet containing 1% cholesterol. Blood sampling and measurement of body weight were carried out at one-week intervals for 4 weeks after the minipump implantation. Following the last blood sampling all animals were killed. The serum cholesterol was determined by an enzymatic method. Unlike E2-17β, 2-MeOE3 exerted little uterotrophic effect and had no effect on body weight even at a high dose. The serum total cholesterol level in low- and high-dose 2-MeOE3 groups exhibited 35.8-46.8% and 47.1-72.2% reductions, respectively, compared with the corresponding control values (administered vehicle alone), while the respective reductions in the E2-17β groups were 5.7-45.1% and 26.0-79.1%. The serum HDL-cholesterol level in the low dose E2-17β group showed significantly higher levels in the 1st and 3rd weeks, and the high-dose E2-17β group, in the 1st, 2nd, and 3rd weeks, compared with the corresponding control values. The high-dose 2-MeOE3 group also exhibited a significantly higher level in the 1st week. These results suggest that 2-MeOE3 lowers serum cholesterol by enhancing not only its catabolism and excretion in the liver, but also by lipoprotein synthesis, and that, unlike the case for E2-17β, the mechanism of action of this hormone involves no estrogen receptors.
The K value=[AFR]2/[RAsA] [DAsA ] (RAsA, reduced form of ascorbic acid; DAsA, oxidized form of ascorbic acid; AFR, ascorbate free radical), and changes in AFR concentration in human serum were examined after exposure to oxygen radicals. After the exposure, RAsA decreased, DAsA increased, and K value increased. Since the K value is constant in healthy subjects, it is regarded to be a clinical index to indicate the attack of oxygen radicals in living system. Whereas changes in AFR concentration in ascorbate solutions showed a one-way decrease after an initial increase, changes in serum were those of a persistent pattern with slight fluctuation after the initial increase. The difference was found to be attributable to the presence of a serum factor that inhibits ascorbate oxidation.
The frequency and mean titer of anti-skeletal muscle (SM) antibody in myasthenic patients with thymoma (64 cases) were significantly high (frequency, 92%; mean titer, 10.1) in all stages of severity, while in myasthenic patients without thymoma (202 cases), they were significantly low (frequency, 24%; mean titer, 2.2). A strong association was found in myasthenic patients between the occurrence of anti-SM antibodies and the presence of thymoma. No correlation was found between titers of anti-SM antibody and those of anti-acetylcholine receptor (AChR) antibody (r=0.036), although myasthenic patients with thymoma had simultaneously high prevalences of anti-AChR (62/64) and anti-SM (59/64) antibodies. Most of the ocular mysthenic patients with and without thymoma had no or extremely low anti-AChR antibody titers (frequency, 25%, 16/65; mean titer, 1.6pmol/ml). Whereas, in all cases of ocular myasthenic patients with thymoma anti-SM antibodies were significantly high titers (frequency, 100%, 8/8; mean titer, 11.0). Reductions in both anti-AChR and anti-SM antibody titers were observed by the serial measurement after thy(mo)mectomy on most of the 10 myasthenic patients with thymoma. Our data on a large number of myasthenic sera reveal that coexistence of anti-SM and anti-AChR antibodies is strongly linked to myasthenia gravis associated with thymoma. The measurement of anti-SM antibodies is recommended for demonstration of thymoma in myasthenic patients before surgery.
Platelet-activating factor (PAF) is known as one of the chemical mediators to induce inflammation and allergy, and is generated by various cell types. The direct effects of PAFs on neutrophils and eosinophils were assessed using several biological parameters, such as migration (in vitro and in vivo methods), aggregation of cells, oxygen radicals (superoxide [O2-], chemiluminescence [CL] and hydrogen peroxide [H2O2]), and bactericidal activity. PAF induced a significant chemotactic response by both neutrophils and eosinophils at concentrations from 10-7 through 10-5M in the agarose plate method, with an optimum concentration at 10-5M for C18PAF and 10-6M for C16PAF. No response was observed by the skin window method, even at a stimulant concentration of 10-4M (600ng). Cellular aggregation was induced by increasing concentrations of C16PAF starting from 10-6M for neutrophils or 10-5M for eosinophils. O2-, CL, and H2O2 production by neutrophils or eosinophils required high concentrations of PAF(10-5M to 10-4M). The data suggest that neutrophils and eosinophils have similar sensitivities and responses to PAF with respect to several different biological functions.