scholarly journals Transient inactivation of phosphatidylethanolamine N-methyltransferase-2 and activation of cytidine triphosphate:phosphocholine cytidylyltransferase during non-neoplastic liver growth

1997 ◽  
Vol 322 (1) ◽  
pp. 151-154 ◽  
Author(s):  
Luciana TESSITORE ◽  
Zheng CUI ◽  
Dennis E. VANCE
Keyword(s):  
Dna Synthesis ◽  
Lead Nitrate ◽  
Time Frame ◽  
Female Rats ◽  
Liver Growth ◽  
Male And Female ◽  
Dietary Choline ◽  
Proliferation Of Hepatocytes ◽  
Liver Proliferation

Phosphatidylethanolamine N-methyltransferase-2 (PEMT2) may contribute to the control of hepatocyte cell division, since its inactivation is associated with several types of liver proliferation including tumorigenesis [Cui, Houweling and Vance (1994) J. Biol. Chem. 269, 24531Ő24533]. To determine if the inactivation of PEMT2 was involved in non-neoplastic proliferation of hepatocytes, we studied the expression of this enzyme in a model of lead nitrate-induced liver proliferation in vivo in rats. A maximal decrease in PEMT activity (60%) and loss of PEMT2 protein (95%) coincided with maximal DNA synthesis and maximal cytidine triphosphate:phosphocholine cytidylyltransferase activity 36 h and 48 h after lead nitrate stimulation in male and female livers respectively. The decrease in expression of PEMT2 corresponded to a decrease in its mRNA. Compared with males, female rats exhibited a 12 h delay in the peak of DNA synthesis, in cytidylyltransferase activity and in the minimum of PEMT2 expression. Supplementation of the rats with dietary choline shifted the female pattern of PEMT2 inactivation, DNA synthesis and activation of cytidylyltransferase to 12 h earlier so that it was similar to the time frame of the expression of these activities in males. These results are consistent with the proposal that the inactivation of PEMT2 may have a role in the regulation of non-neoplastic growth of liver.

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Female Rats ◽  
Male Rats ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Male And Female ◽  
Male And Female Rats ◽  
Arterial Contractility

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice

2016 ◽  
Vol 33 (5) ◽  
pp. 385-405 ◽  
Author(s):  
Kristen R Ryan ◽  
Mark F Cesta ◽  
Ronald Herbert ◽  
Amy Brix ◽  
Michelle Cora ◽  
...  
Keyword(s):  
Animal Studies ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Metalworking Fluids ◽  
Whole Body ◽  
Chemical Components ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rats And Mice

Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m3 for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.

Study on in vivo and in vitro metabolism of dimethylformamide in male and female rats

Toxicology ◽  
1984 ◽  
Vol 29 (3) ◽  
pp. 221-234 ◽  
Author(s):  
V. Scailteur ◽  
E. de Hoffmann ◽  
J.P. Buchet ◽  
R. Lauwerys
Keyword(s):  
In Vitro Metabolism ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

Different effects of (CIS+TRANS) 1,3-dichloropropene in renal cortical slices derived from male and female rats

1999 ◽  
Vol 18 (2) ◽  
pp. 106-110
Author(s):  
Livia Secondin ◽  
Stefano Maso ◽  
Andrea Trevisan
Keyword(s):  
Reduced Glutathione ◽  
Organic Anion ◽  
Female Rats ◽  
Male Rats ◽  
Aminooxyacetic Acid ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cortical Slices

1 Nephrotoxic effects of 1,3-dichloropropene (cis and trans isomers mixture) was investigated in vitro by means of renal cortical slice model in male and female rats, including treatment with metabolism modifiers as an inducer of cytochrome P-450 1A class (β-naphtho-flavone), a reduced glutathione depleting (DL-buthio-nine-[S, R]-sulfoximine), an inhibitor of g-glutamyltransferase (AT-125) and inhibitor of cysteine conjugate β-lyase (aminooxiacetic acid).2 Dose-dependent decrease of p-aminohippurate uptake was observed in male renal cortical slices. Only the high doses (3.0 and 4.0×10-4M) caused a significant loss of organic anion uptake in females.3 β-Naphthoflavone and α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) partially, but significantly, reduced organic anion loss in males. In females, DL-buthionine-[S, R]-sulfoximine significantly increased in females but in males loss of organic anion accumulation caused by 1,3-dichloropropene. Aminooxyacetic acid did not ameliorate 1,3 D effects in vivo and in vitro in male rats. It appeared very toxic for female rats (all rats died) after in vivo injection.4 Sensitivity to nephrotoxicity induced by 1,3-dichlor-opropene in vitro was about double in male than female rats. Reduced glutathione conjugation appeared involved in nephrotoxicity induced in males but in females, probably by means of a chloropropylcysteinylglycine-conjugate formation; slight toxicity in females is likely related to oxidative metabolism.

Inhalation Toxicity and Genotoxicity of Hydrofluorocarbon (HFC)-236fa and HFC-236ea

2000 ◽  
Vol 19 (2) ◽  
pp. 69-83 ◽  
Author(s):  
William J. Brock ◽  
David P. Kelly ◽  
Susan M. Munley ◽  
Karin S. Bentley ◽  
Kathy M. McGown ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Human Lymphocytes ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Seminiferous Tubules ◽  
Inhalation Toxicity ◽  
Male And Female ◽  
Male And Female Rats

The acute, subchronic, and developmental and genetic toxicity of hydrofluorocarbon (HFC)-236fa and HFC-236ea were evaluated to assist in establishing proper handling guidance. In acute inhalation studies, rats were exposed whole body for 4 hours to various concentrations of each isomer. Based on the lack of mortality, the approximate lethal concentration for HFC-236ea for male rats was > 85,000 ppm. For HFC-236fa, the LC50 for males and females (combined) was > 457,000 ppm. Narcotic-like effects, e.g., prostration, incoordination, and reduced motor activity, were observed only during exposure to either isomer, but were not evident after termination of exposure. In cardiac sensitization studies, HFC-236ea induced cardiac sensitization at ≥ 35,000 ppm, with fatal responses occurring at 50,000 ppm and greater. For HFC-236fa, a cardiac sensitization response was observed at 150,000 ppm and greater but not at 100,000 ppm. A fatal cardiac sensitization response was observed in one dog exposed to 150,000 ppm HFC-236fa. In 90-day subchronic inhalation studies, male and female rats were exposed whole body to HFC-236ea at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. Similarly, male and female rats were exposed whole body to HFC-236fa at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. During exposure, narcotic-like effect (reduced acoustic startle response) was observed at 50,000 ppm with both isomers, although there appeared to be an adaptive response to this effect as the study progressed. With HFC-236ea, dilatation of the seminiferous tubules, without effects on germ or Sertoli cells, was observed only in rats at 50,000 ppm. No other effects on in-life measures or on clinical or anatomic pathology, including histopathology, were observed for either isomer. In rat developmental toxicity studies, no evidence of embryotoxicity or teratogenicity was observed with either isomer exposed up to 50,000 ppm during gestational days 7 to 16. Also, no developmental toxicity was observed in rabbits exposed to HFC-236fa at concentrations of up to 50,000 ppm during gestational days 7 to 19. Neither of the HFC-236 isomers was mutagenic in the Ames reverse mutation assay or clastogenic in the chromosomal aberration assay with human lymphocytes. No increase in chromosomal aberrations was observed in in vivo micronucleus studies with either isomer.

Phosphatidylinositol 4,5-bisphosphate stimulates alveolar epithelial fluid clearance in male and female adult rats

2011 ◽  
Vol 301 (5) ◽  
pp. L804-L811 ◽  
Author(s):  
Edgar E. Kooijman ◽  
Stephanie R. Kuzenko ◽  
Denghuang Gong ◽  
Michael D. Best ◽  
Hans G. Folkesson
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Na Channel ◽  
Alveolar Fluid Clearance ◽  
Membrane Phospholipids ◽  
Adult Rats ◽  
Male And Female ◽  
Alveolar Epithelial ◽  
Male And Female Rats

Cell membrane phospholipids, like phosphatidylinositol 4,5-bisphosphate [PI( 4 , 5 )P2], can regulate epithelial Na channel (ENaC) activity. Gender differences in lung ENaC expression have also been demonstrated. However, the effects in vivo on alveolar fluid clearance are uncertain. Thus PI( 4 , 5 )P2 effects on alveolar fluid clearance were studied in male and female rats. An isosmolar 5% albumin solution was intrapulmonary instilled; alveolar fluid clearance was studied for 1 h. Female rats had a 37 ± 19% higher baseline alveolar fluid clearance than male rats. Bilateral ovariectomy attenuated this gender difference. Compared with controls, PI( 4 , 5 )P2 instillation (300 μM) increased alveolar fluid clearance by ∼93% in both genders. Amiloride or the specific αENaC small-interfering RNA inhibited baseline and PI( 4 , 5 )P2-stimulated alveolar fluid clearance in both genders, indicating a dependence on amiloride-sensitive pathways. The fraction of amiloride inhibition was greater in PI( 4 , 5 )P2-instilled rats (male: 64 ± 10%; female: 70 ± 11%) than in controls (male: 30 ± 6%; female: 44 ± 8%). PI( 4 , 5 )P2 instillation lacked additional alveolar fluid clearance stimulation above that of terbutaline, nor did propranolol inhibit alveolar fluid clearance after PI( 4 , 5 )P2 instillation, indicating that PI( 4 , 5 )P2 stimulation was not secondary to endogenous β-adrenoceptor activation. PI( 4 , 5 )P2 amine instillation resulted in an intermediate alveolar fluid clearance stimulation, suggesting that, to reach maximal alveolar fluid clearance stimulation, PI( 4 , 5 )P2 must reside in cell membranes. In summary, PI( 4 , 5 )P2 instillation upregulated in vivo alveolar fluid clearance similar to short-term β-adrenoceptor upregulation of alveolar fluid clearance. PI( 4 , 5 )P2 stimulation was mediated partly by increased amiloride-sensitive Na transport. There exist important gender-related effects suggesting a female advantage that may have clinical implications for resolution of acute lung injury.

scholarly journals In vivo determination of body composition by tritium dilution in the rat

1979 ◽  
Vol 41 (3) ◽  
pp. 625-628 ◽  
Author(s):  
Nancy J. Rothwell ◽  
M. J. Stock
Keyword(s):  
Body Water ◽  
Female Rats ◽  
Indirect Methods ◽  
Male And Female ◽  
Male And Female Rats ◽  
Significant Difference ◽  
Total Body ◽  
Direct And Indirect Methods

Total body water was determined in vivo by tritium dilution in thirty-two male and female rats. Body water obtained by tritium dilution and body fat calculated from this value correlated significantly with body water and fat obtained by analysis (r 0.985, 0.855 respectively). There was no significant difference between values for fat assessed by the direct and indirect methods.

EFFECTS OF TESTOSTERONE ON PITUITARY CORTICOTROPHIN AND ADRENAL STEROID SECRETION IN MALE AND FEMALE RATS

1963 ◽  
Vol 43 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Julian I. Kitay
Keyword(s):  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Male And Female ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Male And Female Rats

ABSTRACT Administration of a depot testosterone preparation to male and female rats resulted in no change in body or pituitary weight in either sex. Pituitary corticotrophin content was unaltered in male animals but was reduced in females. Adrenal weights and adrenal RNA and DNA contents were decreased in both sexes. Plasma corticosterone concentrations were unaffected in males but were reduced in female rats after stress or corticotrophin injection. Hepatic reduction of ring A in vitro and biological half-life of corticosterone in vivo were unchanged in male animals but impaired in females. Testosterone administration to intact male rats significantly increased adrenal steroidogenesis measured in vitro. A significant decrease in steroid production was found in intact females but increased steroidogenesis was observed in adrenals from testosterone-treated oophorectomized animals. No effect was obtained following addition of testosterone directly in vitro. The data suggest that testosterone leads both to diminution of corticotrophin secretion and enhancement of adrenal steroid secretory capacity. In intact female rats, these effects are complicated by suppression of oestrogen secretion, the effects of which have been reported previously.

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