EXPERIMENTAL EVALUATION OF DIURETICS IN THE RAT

1956 ◽  
Vol 34 (5) ◽  
pp. 903-911 ◽  
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.

1956 ◽  
Vol 34 (1) ◽  
pp. 903-911
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


1984 ◽  
Vol 103 (3) ◽  
pp. 317-325
Author(s):  
A. K. Brar ◽  
G. Fink

ABSTRACT The effects of catechol oestradiol and catechol oestrone on the release of LH and prolactin were investigated in immature male and female Wistar rats. In male rats both catechol oestradiol and catechol oestrone significantly increased the plasma concentration of LH, and catechol oestradiol but not catechol oestrone significantly increased the plasma concentration of prolactin and decreased the pituitary concentration of LH. The parent oestrogens, oestradiol-17β and oestrone, had no effect on plasma LH concentrations, but both increased significantly the plasma concentration of prolactin, and oestrone but not oestradiol-17β increased the pituitary concentration of LH. In immature female rats, catechol oestradiol inhibited the surge of LH and the increase in uterine weight induced by injecting pregnant mare serum gonadotrophin (PMSG). The injection of oestrone induced an increase in the plasma concentration of LH which was about nine times greater than that produced by oestradiol-17β. There were no significant differences in the effects of these steroids on plasma prolactin concentration. These results (i) confirm that in the immature male rat catechol oestrogens can stimulate LH release and show that catechol oestradiol can increase prolactin release, (ii) show that catechol oestradiol can inhibit the stimulatory effects of PMSG on LH release and uterine weight in the immature female rat, and (iii) demonstrate that oestrone can stimulate LH release in the immature female rat. J. Endocr. (1984) 103, 317-325


2017 ◽  
Vol 233 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Marion Walser ◽  
Linus Schiöler ◽  
Jan Oscarsson ◽  
Maria A I Åberg ◽  
Ruth Wickelgren ◽  
...  

The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron–haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5′-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.


2020 ◽  
Vol 17 (2) ◽  
pp. 163 ◽  
Author(s):  
Nicoleta Vedeanu ◽  
Cezara Voica ◽  
Dana Alina Magdas ◽  
Bela Kiss ◽  
Maria-Georgia Stefan ◽  
...  

Environmental contextAlthough ruthenium is a technology-critical element used in several new industries, little is known about its environmental impact or possible human health risks. We report a toxicological evaluation of laboratory animals during co-exposure to ruthenium and silver. We identified interactions between the two elements that could lead to unwanted biological effects. AbstractRuthenium is one of the rarest metals on Earth that is classified as a technology-critical element (TCE). Silver, however, is well known for its antibacterial and immunostimulant properties. The increasing use of Ru and Ag in medicine and daily life makes simultaneous exposure possible, with unknown pharmacokinetic or toxicological consequences for the human organism. Thus, the present study investigated the influence of co-exposure to RuIII on the subacute toxicity of Ag ions in rats after repeated daily administration for 28 days of low doses by oral gavage. The subacute toxicity was investigated by the evaluation of several biochemical and hematological parameters, evaluation of specific oxidative stress biomarkers from liver and kidney, and histopathological investigation of liver and kidney tissue samples after 28 days of exposure in female rats. In addition, Ag and Ru concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) in urine, liver and kidney parenchyma in male rats. The obtained results showed that co-exposure to low doses of RuIII and Ag did not produce any significant biochemical, hematological or histopathological alterations in the treated female rat groups, except for an increased red cell distribution width (RDW) value. A decrease of urinary excretion of Ag and of the Ag concentration in kidneys was observed in the male rat group co-exposed to RuIII and Ag. This is the first invivo study investigating the toxic effect of co-exposure to low doses of Ag and Ru ions, and the obtained results may justify further research on this subject, mainly on the investigation of possible competitive mechanisms.


1964 ◽  
Vol 47 (1) ◽  
pp. 37-50 ◽  
Author(s):  
H. E. Swanson ◽  
J. J. van der Werff ten Bosch

ABSTRACT The interaction between dose and time of administration of testosterone propionate (TP) on the development of sexual function was studied by giving a single dose of 5, 10, 50 or 500 μg TP to young rats of both sexes on the day of birth (day 1) or on day 2, 4 or 5. The effectiveness of androgen administration before birth was studied by giving a single injection of 2500 μg TP to pregnant rats on day 19 to 22 after conception. Pre-natal administration had no effect on the function of the ovaries of female offspring, although the dose was sufficient to cause masculinization of the external genitalia. The weight of the testes and accessories of the male offspring were not affected. The effects of post-natal TP administration on ovarian function varied with the dose and with the time of administration. Threshold doses (5 and 10 μg) were more effective the earlier they were given after birth. With these small doses, most of the rats had normal luteinized ovaries at 10 weeks and were able to bear and suckle normal litters. Some time later ovulations ceased so that at 21 weeks they were no longer fertile; at 27 weeks there were no more corpora lutea in the ovaries. In males, a dose of 50 μg of TP or more resulted in permanently reduced weight of testes, seminal vesicles and prostate. The earlier the treatment, the more marked was the depression of weight. From these results and others reported in the literature the following deductions can be made: (1) the critical period of brain sensitivity to physiological amounts of androgen probably lies between days 4 and 6 (day of birth counted as day 1); (2) a rough estimate of the amount of androgen secreted by the newborn male rat during the critical period would seem to be the equivalent of a single injection of 5–50 μg TP; (3) after the physiological critical period has elapsed a female rat can still be »masculinized« if a high dose of TP is given, up to a period of between 10–20 days after birth.


2005 ◽  
Vol 19 (5) ◽  
pp. 1181-1190 ◽  
Author(s):  
Megumi Endo ◽  
Yoshiki Takahashi ◽  
Yasumasa Sasaki ◽  
Tetsuya Saito ◽  
Tetsuya Kamataki

Abstract The expression of CYP2C12 by GH occurs in female but not in male rat livers. Direct injection of the CYP2C12 promoter-luciferase gene into male rat livers showed that the CYP2C12 promoter was active in both male and female rats. Thus, to further examine one or more factors that regulate the gender-related expression of CYP2C12, male rats were treated with trichostatin A, a specific inhibitor of histone deacetylase capable of condensing the chromatin structure. Interestingly, the expression of CYP2C12 by GH was seen even in the livers of male rats, indicating that histone deacetylase contributes to the suppression of CYP2C12 expression in male rats. Deoxyribonuclease I hypersensitive assay using nuclei from the livers of male or female rats revealed that the chromatin structure of the CYP2C12 gene was gender specific: a hypersensitive site at a position −4.2 kb containing GH-responsive element that bound to signal transducer and activator of transcription 5 (STAT5), termed as HS (hypersensitive site) 1, was specific for female rat livers, whereas a hypersensitive site at a position −3 kb, designated as HSm (male-specific hypersensitive site), was characteristic of male rat livers. A −3425/−3275 region within HSm functioned as a negative regulatory region, when the region was inserted in front of simian virus 40 promoter. Gel shift assay demonstrated that both CCAAT/enhancer-binding protein α and β bound to the −3425/−3275 region. Based on these results, we conclude that the gender-related expression of the CYP2C12 gene results from the inaccessibility of to STAT5 to the GH-responsive element by chromatin condensation seen in male rat livers, and from the presence of the male-specific HSm that acts as a silencer.


1973 ◽  
Vol 72 (1) ◽  
pp. 1-8 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.


1963 ◽  
Vol 43 (2) ◽  
pp. 246-254 ◽  
Author(s):  
G. H. Zeilmaker

ABSTRACT The functional activity of artificially induced corpora lutea in isologous ovaries transplanted into castrated male rats has been studied. Criteria for progesterone production were the morphology of vaginal transplants and the distribution of sudanophilic material in the corpus luteum cells. It was found that spontaneous functional activity of the corpora lutea did not occur in short-term experiments. Progesterone production was observed, however, in animals also bearing an isotransplanted (either male or female) pituitary gland, and in animals which received daily injections of reserpine. It is suggested that the normal influence of the central nervous system on the secretion of luteotrophic hormone is inhibitory in male as well as in female animals. Some aspects of the induction and maintenance of luteal function in castrated male rats bearing a transplanted ovary have been studied and compared with similar phenomena in the female rat. A real pseudopregnancy, i. e. maintained by the pituitary in situ during a defined period, as can be observed in female rats, could not be induced in these animals. In animals also bearing an isografted pituitary gland, luteolysis was not observed in experiments lasting up to 45 days. It is suggested that these findings may be correlated with the way in which the luteinizing hormone is secreted in the male rat.


2014 ◽  
Vol 64 (2) ◽  
pp. 179-188
Author(s):  
Slobodan Malobabić ◽  
Ivan Jovanović ◽  
Olivera Lozanče ◽  
Sladjana Ugrenović ◽  
Zoran Zorić ◽  
...  

Abstract Morphometric parameters of the lateral ventricle choroid plexus epithelial cells (average area, perimeter, bounding rectangle area, average nuclear area, nuclear perimeter, nuclear circularity and average nucleocytoplasmic ratio) were studied in postnatal and juvenile (10th, 16th and 38th postnatal days) 15 male and 15 female rats. The results were statistically analyzed by factorial ANOVA. Mean values of epithelial cells area, bounding rectangle area and perimeter were significantly higher in 16 days old, than in 10 and 38 days old rats. Opposite to this, the nucleocytoplasmic ratio was lower in the 16 days old, than in 10 and 38 days old rats. Average nuclear area and perimeter showed similar trends, while nuclear circularity increased from the 10th to the 38th day. Significant sex differences were in the epithelial cells area, bounding rectangle area and perimeter, being higher in males than in females in both 16 and 38 days groups. Nucleocytoplasmic ratio was higher in 10 days old male rats, but lower in 16 and 38 days old male rats. Generally, choroid epithelial cells size increased on the 16th and then decreased on the 38th day, but still remained higher compared to the 10th day. Nuclear size after increasing on day 16, also decreased on day 38, but to values lower than on day 10. The general decrease of nucleocytoplasmic ratio which accompanied these changes indirectly suggests a functional decrease. In the investigated period the male rat choroid epithelial cells were larger, but their nucleocytoplasmic ratio, which suggests the functional status, was lower than in females, indicating sex differences in the growth dynamics of the rat choroid plexus.


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