A comparative study of drug metabolizing enzymes in adrenal glands and livers of rats and chickens

1. Drug metabolizing enzymes (cytochrome P450, glutathione-S-transferase, carboxylesterase) were compared in livers and adrenal glands from rats and chickens. 2. Quantities of cytochrome P450 in chicken liver and adrenal glands were less than in rat liver and adrenals. 3. Activities of carboxylesterase and of glutathione-S-epoxide transferase were similar in livers of rats and chickens. 4. In the chicken, activities of carboxylesterase and of glutathione-S-epoxide transferase were less in adrenal glands than in livers. 5. Carboxylesterase enzyme activities in adrenal glands of chickens were more sensitive to inhibition by antiesterase agents than were carboxylesterase enzyme activities in liver.     

Morphofunctional characteristics of the adrenal glands in the progeny from females with experimental hypothyroidism]

Under study were the morphofunctional features of adrenal glands of 1, 10, 20, 30 and 40-day-old rats born by females with experimental hypothyrosis obtained by bilateral subtotal parathyroidectomy and blocade of the gland functioning by mercazolil (3 mkg/kg). The experimental treatment preceded pregnancy. The antithyroid drug was injected during pregnancy and lactation. The posterity of experimental animals was established to have a decreased need in oxygen as compared with controls. Their adrenal glands were of less weight (especially in off-springs of parathryodidectomized rats in the neonatal period). There are a number of morphometrical and histochemical signs suggesting the suppression of the functioning of the cortical and medullary substance, including the period of adaptation of the organism to the extrauterine life.     

Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats

A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress.     

The mechanism of liver splanchnomegaly produced by a transplantable pituitary mammotropic tumor in rats.

The mechanism of liver splanchnomegaly developed in rats bearing a transplantable pituitary mammotropic tumor which secretes large amounts of ACTH and prolactin has been studied. The results indicate that in the first phase of tumor growth liver enlargement could be due to hypertrophy, and later mainly to hyperplasia which overcomes hypertrophy. The adrenal glands were found to play an essential role in the process of liver splanchnomegaly because adrenalectomy prevented the disproportional growth of the liver. Evidence is presented showing that glucocorticoids are the dominant hormones responsible for the development of liver splanchnomegaly.     

Comparative localization of aldehyde oxidase and xanthine oxidoreductase activity in rat tissues

The distribution of aldehyde oxidase activity was evaluated in unfixed cryostat sections from tissues of male Wistar rats using a tissue protectant, polyvinyl alcohol, with Tetranitro BT as a final electron acceptor. The distribution of aldehyde oxidase activity was compared with that of xanthine oxidoreductase. The enzyme histochemical method demonstrated aldehyde oxidase activity in the epithelium of the tongue, renal tubules and bronchioles, as well as in the cytoplasm of liver cells. Such activity was not detected in oesophagus, stomach, spleen, adrenal glands, small or large intestine or skeletal and heart muscle fibres. In contrast, xanthine oxidoreductase activity was demonstrated in the tongue, renal tubules, bronchioles, oesophageal, gastric, small and large intestinal epithelial cells, adrenal glands, spleen and liver cytoplasm but not in skeletal and heart muscle fibres. The significance of the ubiquitous distribution of aldehyde oxidase activity, especially in surface epithelial cells from various tissues, except for the gastrointestinal tract, is unclear. However, aldehyde oxidase may possess some physiological activity other than in the metabolism of N-heterocyclics or of certain drugs. © 1998 Chapman & Hall     

Distribution and colocalization of nitric oxide synthase and NADPH-diaphorase in adrenal gland of developing,adult and aging Sprague-Dawley rats

The distribution and colocalization of nitric oxide synthase and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) was investigated in the adrenal gland of developing, adult and aging rats with the use of immunohistochemical and histochemical techniques. Nitric oxide synthase-immunoreactive neurons within the adrenal gland were found from the 20th day of gestation onwards. During early development the neurons were found as small clusters of smaller-size cells compared to those observed in the adult gland. Their number reached that of adult level by the 4th day after birth, and in the glands from aging rats a 28.6% increase was observed. Whilst no immunofluorescence was seen in chromaffin cells during early development, some cells from glands of aging rats showed nitric oxide synthase-immunoreactivity with varying intensity. The immunoreactive neurons from postnatal rat adrenals were also positive for NADPH-diaphorase, whilst those in prenatal rats were negative or lightly stained. Nitric oxide synthase-immunoreactive nerve fibres were present in all adrenal glands examined from the 16th day of gestation onwards. A considerable degree of variation in the distribution of immunoreactive fibres both in medulla and outer region of cortex at the different age groups was observed and described. Most, but not all, nitric oxide synthase-immunoreactive nerve fibres also showed NADPH-diaphorase staining.     

Role of the adrenal glands in the cytostatic action mechanism of antitumor antibiotics

The state of the steroidogenic function of the adrenal glands, lipid spectrum of the adrenal gland tissue and metabolism rate of 11-oxycorticosteroids (11-OCS) in the liver tissue and their levels in the blood plasma were studied on rats after a single administration of karminomycin in a dose of LD50 (1.55 mg/kg). The hormones of the adrenal cortex were shown to play a definite role in the mechanism of the karminomycin damaging effect. Dependence of the changes on the time of the drug effect was noted. The shifts were of a reversible character. No direct toxic damages in the tissue of the adrenal glands were observed. Only an increase in the 11-OCS blood levels and a decrease in the steroid metabolism in the liver tissue were shown. The latter must be due to the direct cytotoxic effect of karminomycin on the tissue of this organ.     

Influence of ACTH secreting tumor (MtTF4) on fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy

Pregnant female rats with ACTH secreting tumor (MtTF4) have prolonged pregnancy and cannot deliver. The fetuses of tumor bearing females have in prolonged pregnancy on days 24 and 25 of pregnancy greater body weight and smaller adrenal weight as compared to intact fetuses of the 22nd day of pregnancy. The fetal adrenal glands converted to vitro 4-14C progesterone to radioactive 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. Fetal adrenal glands in prolonged pregnancy synthetized in vitro less amount of radioactive DOC, B and 18-OH-DOC. A negative relationship exists between the maternal corticosterone which passes the placenta to fetuses and corticosteroidogenesis of fetal adrenal glands. These results indicate the possibility that fetal rat adrenal glands with their corticosteroids participate in pregnancy and influence normal delivery.     

Histochemical and morphometrical changes in the adrenal glands in the course of circulatory failure.

The histological and biochemical changes in adrenal function has been studied in 50 male cats with circulatory failure. The adrenal glands were examined by morphometric, histochemical and histoenzymological methods after a preliminarily study of the histoenzymological profile of the adrenal glands in intact animals. Five hours after hypotension induced by intravenous injection of trimethaphan and 5 hours after a single massive bleeding, a decrease in adrenal function was observed. Adrenal insufficiency especially of the glucocorticoid release in the course of acute circulatory failure can be considered as a peculiar adaptation of the organism to preserve its life. The demonstrated decrease of adrenal function in the first hours of hypoxia may help in planning hormonal therapy under suitable conditions.     

Immunoreactive luliberin in the visceral organs of rats]

The distribution of luliberin (luteinizing hormone-releasing hormone, LH-RH) was studied. LH-RH-like factor showing analogous immunochemical and chromatographic properties was detected in the liver, kidneys, duodenum, pancreas, adrenal glands and heart of rats. The concentration of immunoreactive LH-RH in the liver, kidneys, duodenum, pancreas and adrenal glands was nearly equal (5 to 7 pg per mg of methanol extract obtained from acetic acid extract of acetone powder), its concentration in the heart being somewhat lower (2 pg per mg of extract). Only minute amounts of this factor were present in blood cells. Immunoreactive LH-RH found in visceral organs may be of hypothalamic origin or may be synthesized in these organs (in situ).     

不同周龄SD大鼠脏器重量及其变化趋势分析

目的分析不同周龄SD大鼠的脏器重量及其变化趋势,为评判药物毒性反应提供理论参考。方法分别选取试验第13、26、52、78和104周对照组动物脑、脾脏、心脏、肺脏、肝脏、肾脏、肾上腺、睾丸、卵巢的重量数据并分析。结果从13～104周SD雌鼠脑、脾脏、心脏、肺脏、肝脏、肾脏、肾上腺、卵巢的重量呈升高趋势。从13～104周SD雄鼠脑、脾脏、心脏、肺脏、肝脏、肾脏重量均重于雌鼠,但雌鼠肾上腺重量、脏体比和脏脑比均显著高于雄鼠。结论本研究首次在国内建立了符合我国实验动物现状的,不同周龄SD大鼠的脏器重量背景数据和参考值范围,并分析了不同周龄SD大鼠脏器重量变化趋势。     

Stress-induced Morphohistochemical and Functional Changes in Rat Adrenal Cortex, Testis and Major Salivary Glands

The effect of repeated stress (1 h of daily immobilization for seven consecutive days) on the adrenal cortex of young adult male albino rats was evaluated by morphohistochemical methods and plasma assays; at the same time, testes and major salivary glands, as steroid-producing and -depending organs, respectively, were examined. Morphological and histochemical changes were found in the adrenal cortex, testis and submaxillary gland, though varying in degree and extent depending on the gland examined. Corticosterone and progesterone plasma levels increased, in agreement with the lipid depletion observed in the zona fasciculata, while testosterone and androstenedione decreased, as confirmed by the less marked enzymatic activity in the Leydig cells. The study thus proves that repeated stress, even of temporary duration, is able to influence directly or indirectly the morphofunctional state of the three examined glands, suggesting a functional linkage.     

A comparison of the low-density-lipoprotein receptor from bovine adrenal cortex, rabbit and rat liver and adrenal glands by lipoprotein blotting.

This paper describes the use of lipoprotein blotting to detect low-density-lipoprotein (LDL) receptors in rat and rabbit liver and adrenal glands and in bovine adrenal glands. Using this technique we show that the rabbit and rat liver LDL receptors have Mr values of 128000 and 145000 respectively. Mr values for the rabbit, rat and bovine adrenal receptors are 131000, 142000 and 132000 respectively. Differences between the bovine adrenal and rat liver receptors are not due to differences in the degree of sialylation. Lipoprotein blotting can be used to detect dietary- and drug-induced changes in the concentrations of LDL receptors. When rabbits are fed on a cholesterol-rich diet, liver LDL receptors cannot be detected, consistent with the suppression of hepatic LDL receptors by cholesterol feeding. Pharmacological doses of 17 alpha-ethinyloestradiol cause a marked increase in hepatic LDL-receptor activity in the rat. This is accompanied by a corresponding increase in the number of LDL receptors detected by lipoprotein blotting. The Mr of the induced receptor is identical with that of the receptor from control rats, which suggests that the induced receptors are produced by the same gene as LDL receptors normally present in the liver.     

Mulberry leaves protect rat tissues from immobilization stress-induced inflammation

The ability of the antioxidants in the mulberry leaves to protect Sprague-Dawley rats from injuries caused by immobilization stress was studied as an indicator of the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and total antioxidant activity (TAA) in the plasma and tissues were measured. There were hypertrophy of the adrenal glands and kidneys, significant increased levels of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized rats. Antioxidants in the mulberry leaf extract suppressed the increase of nitrite and TBARS. Adrenal glands appeared to be the target organ of the antioxidants in the leaf extract. The low dose mulberry antioxidants were more effective than pure rutin (4 mg/day) to protect the cells against inflammation and peroxidation induced by stress.     

Decreased density of endothelin binding sites in adrenal glands but not in aorta,of long term infarcted rats

Endothelins (Et-s) are biologically active peptides which play a physiological and pathological role in the cardiovascular regulation. The aim of our study was to verify, in a model of experimental long term myocardial ischemia (15 weeks) in rats, whether there was a modification in the ET binding sites of aorta and adrenal glands. Additionally, Ang II binding sites in adrenal glands were studied. The principal finding of the present study was the down-regulation of ET binding sites in adrenal glands of chronic infarcted rats, whereas no modification of binding parameters for Et-l, in thoractic aorta, nor for Ang II, in adrenal glands, were found.     

Oleoyl-estrone increases adrenal corticosteroid synthesis gene expression in overweight male rats

Oleoyl-estrone (OE) induces a marked loss of body fat in rats by maintaining energy expenditure, body protein and blood glucose despite decreasing food intake. OE increases glucocorticoids, but they arrest OE lipid-mobilization. We studied here whether OE induces a direct effect on adrenal glands function as part of this feedback regulation. Dietary overweight male rats were given oral 10 nmol/g OE gavages for ten days. A group (PF) of pair-fed to OE rats, and controls received vehicle-only gavages. OE rats lost slightly more body than PF, but had larger adrenal glands. Tissue corticosterone levels, and gene expressions for glucocorticoid-synthesizing enzymes were increased in OE versus controls and PF; thus, we assumed that adrenal growth affected essentially its cortex since OE also lowered the expression of the medullar catecholamine synthesis enzyme genes. Serum corticosterone was higher in PF than in OE and controls, but liver expression of corticosteroid-disposing steroid 5α-reductase was 3× larger in OE than PF and controls. Circulating glucocorticoids changed little under OE, in spite of higher adrenal gland and liver content, hinting at modulation of glucocorticoid turnover as instrumental in their purported increased activity. In conclusion, we have observed that OE considerable enhanced the expression of the genes controlling the synthesis of glucocorticoids from cholesterol in the rat and increasing the adrenal glands’ corticosterone, size and cellularity, but also the liver disposal of corticosteroids, suggesting that OE increases corticosterone synthesis and degradation (i.e. serum turnover), a process not driven by limited energy availability but directly related to the administration of OE.     

The significance of corticosteroid insufficiency in the mechanisms of toxicosis in experimental listeriosis

The infection of mice with Listeria led, in case of the development of an acute generalized form of the disease, to the sharp decrease of the content of ascorbic acid and to the nearly complete delipidization of the glomerular zone of the adrenal cortex, which was indicative of the development of relative adrenal insufficiency. The most pronounced histomorphological and histochemical changes occurred simultaneously with the maximum accumulation of Listeria in the adrenal glands. The administration of hydrocortisone at the period of the development of acute infection produced a temporary decrease in the manifestations of toxicosis. The maximum protective effect was achieved by combined glucocorticoid and antibiotic therapy.     

Effect of angiotensin II on angiotensinogen production in adrenalectomized rats

The present study was performed to examine the effect of angiotensin II on hepatic angiotensinogen production in adrenalectomized rats. The hepatic angiotensinogen mRNA levels in rats without adrenal glands increased 2.8-fold 4 h after the start of angiotensin II infusion. In intact rats with adrenal glands, the hepatic angiotensinogen mRNA levels increased 2.7-fold 4 h after the start. The angiotensin II infusions did not only increase angiotensinogen mRNA levels in intact rats but also increased those in adrenalectomized rats. The results suggest that the angiotensinogen response to ANG II was not dependent on adrenal glucocorticoid.     

Effect of chronic alcohol administration on the adrenals thyroid, pancreatic islands and liver of male albino rats

In response to chronic oral ethanol administration, the adrenals, thyroid glands, pancreatic islets, and livers of male white rats show histological and chemomorphological reactions. Cytological, karyometrical, and histochemical findings from adrenal medulla indicate increased secretion and synthesis of catecholamines. Adrenal cortex shows morphokinetic changes within the meaning of progressive transformation. About 1 h after the last ethanol administration, there are no signs of inappropriate insulin secretion in the B-cells of pancreatic islets. In addition to a small lipid storage and a marked decrease of glycogen contents, the hepatocytes show karyometrical sign of an increased cell metabolism.