Sex Difference In Platelet Response To Aspirin Treatment

1981 ◽  
Author(s):  
N S Nicholson ◽  
S L Smith ◽  
R N Saunders
Keyword(s):  
Arachidonic Acid ◽  
Sex Difference ◽  
In Vitro Study ◽  
Female Rats ◽  
Platelet Response ◽  
Male And Female Rats ◽  
Males And Females ◽  
Spontaneous Aggregation

This study was done to determine if a sex difference in response to aspirin similar to that seen in the clinic could be demonstrated in an animal model with hyperactive platelets. The platelet hyperactivity which results in the spontaneous formation of platelet aggregates in retired breeder rats was reduced in both male and female rats by sulfinpyrazone, dipyridamole and indomethacin administered at 20 mg/kg. Aspirin blocked spontaneous aggregation in the male, but had no effect in the female even at doses of 100 mg/kg. Because aspirin is known to be an inhibitor of cyclooxygenase, the metabolism of arachidonic acid was studied in these rats. Arachidonic acid at 20 mg/kg was active in reducing spontaneous aggregation in the male, but had no effect in the female. However, in an in vitro study of the metabolism of arachidonic acid, no significant differences were seen between males and females in the conversion of arachidonic acid to PGF2α, PGE2, TXB2 or HHT. Aspirin was equally effective in both males and females in blocking the in vitro conversion of arachidonic acid via the cyclooxygenase pathway. The retired breeder rat provides a system for meaningful investigations toward understanding the human sex-related differences in platelet sensitivity with aspirin, although the mechanisms of the in vivo male/female platelet sensitivity have not been explained by in vitro studies thus far.

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.

Effect of age on the 3,5,3′-tri-iodothyronine-induced increase in sugar uptake in rat thymocytes

1986 ◽  
Vol 110 (3) ◽  
pp. 511-515 ◽  
Author(s):  
J. Segal ◽  
B. R. Troen
Keyword(s):  
Female Rats ◽  
In Vivo Studies ◽  
Sugar Uptake ◽  
Male And Female Rats ◽  
Old Rats ◽  
Effect Of Age ◽  
Age And Sex ◽  
In Cells

ABSTRACT The effect of age on the responsiveness of rat thymocytes to 3,5,3′-tri-iodothyronine (T3) was studied. It has been demonstrated previously that the plasma membrane-mediated effect of T3 to increase sugar uptake by rat thymocytes is influenced by age and sex. In both sexes, T3 given in vitro stimulated sugar uptake in cells from animals of 15 days of age, had no effect at 21 days and was again effective at 26 days. In the male, thymocytes from animals of 40 days of age and older were refractory to T3. However, in the female, T3, although less effective than in cells from 26-day-old animals, remained stimulatory in cells from 40- and 60-day-old rats. T3 had no effect in cells from animals of 90 days of age and older. In in-vivo studies in which female rats of 26, 60 and 90 days of age were first injected with T3 and 1 h later with [3H]2-deoxyglucose, the responsiveness of thymocytes to T3 also declined progressively with advancing age; T3 was most effective in cells from 26-day-old animals, less stimulatory in 60-day-old and essentially without effect in cells from 90-day-old animals. From these observations we have concluded that in both male and female rats the responsiveness of thymocytes to T3 declines progressively with age, and that this decline occurs at an earlier age in cells obtained from males. J. Endocr. (1986) 110, 511–515

scholarly journals Single and Repeated Oral Dose Toxicity and Genotoxicity of the Leaves of Butterbur

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1963
Author(s):  
Sangsu Park ◽  
Jeongin Lim ◽  
Kyung Tae Lee ◽  
Myung Sook Oh ◽  
Dae Sik Jang
Keyword(s):  
Oral Dose ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Hot Water ◽  
Female Rats ◽  
Human Consumption ◽  
In Vitro Tests ◽  
Male And Female Rats

Butterbur (Petasites japonicus (Siebold & Zucc.) Maxim) leaves are available to consumers in the marketplace, but there is no guarantee that they are safe for human consumption. Previously, we demonstrated that hot water extracts of P. japonicus leaves (KP-1) had anti-inflammatory properties and attenuated memory impairment. However, data regarding KP-1 toxicity are lacking. This study assessed the safety of KP-1 by examining oral and genotoxic effects using in vivo and in vitro tests, respectively. In a single oral dose toxicity and two-week repeated oral dose toxicity study, we observed no toxicologically significant clinical signs or changes in hematology, blood chemistry, and organ weights at any dose during the experiment. Following a thirteen-week repeated oral dose, toxicity, hyperkeratosis, and squamous cell hyperplasia of the limiting ridge in the stomach were observed. The no observable adverse effect level (NOAEL) was found to be 1250 mg/kg/day in male and female rats. However, hyperkeratosis and hyperplasia were not considered to be of toxicological significance when extrapolating the NOAEL to humans because the limiting ridge in the stomach is species-specific to rats. Therefore, in our study, the NOAEL was considered to be 5000 mg/kg/day when the changes in the stomach’s limiting ridge were discounted. Moreover, in vitro bacterial reverse mutations and chromosomal aberrations in Chinese hamster lung (CHL) cells and the in vivo micronucleus in Institute of cancer research (ICR) mice assays showed that KP-1 possessed no mutagenicity. Although additional research is required, these toxicological evaluations suggest that KP-1 could be safe for human consumption.

scholarly journals Sex-Dependence in the Effect of Pharmaceutical Excipients: Polyoxyethylated Solubilising Excipients Increase Oral Drug Bioavailability in Male but Not Female Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 228 ◽  
Author(s):  
Yang Mai ◽  
Liu Dou ◽  
Christine M. Madla ◽  
Sudaxshina Murdan ◽  
Abdul W. Basit
Keyword(s):  
Ussing Chamber ◽  
Drug Formulation ◽  
Female Rats ◽  
Oral Drug ◽  
Dependent Manner ◽  
Drug Bioavailability ◽  
Pharmaceutical Excipients ◽  
Males And Females

It is known that males and females respond differently to medicines and that differences in drug behaviour are due to inter-individual variability and sex specificity. In this work, we have examined the influence of pharmaceutical excipients on drug bioavailability in males and females. Using a rat model, we report that a portfolio of polyoxyethylated solubilising excipients (polyethylene glycol 2000, Cremophor RH 40, Poloxamer 188 and Tween 80) increase ranitidine bioavailability in males but not in females. The in vivo sex and excipient effects were reflected in vitro in intestinal permeability experiments using an Ussing chamber system. The mechanism of such an effect on drug bioavailability is suggested to be due to the interaction between the excipients and the efflux membrane transporter P-glycoprotein (P-gp), whose expression in terms of gene and protein levels were inhibited by the solubilising agents in male but not in female rats. In contrast, the non-polyoxyethylated excipient, Span 20, significantly increased ranitidine bioavailability in both males and females in a non-sex-dependent manner. These findings have significant implications for the use of polyoxyethylated solubilising excipients in drug formulation in light of their sex-specific modulation on the bioavailability of drugs that are P-gp substrates. As such, pharmaceutical research is required to retract from a ‘one size fits all’ approach and to, instead, evaluate the potential impact of the interplay between excipients and sex on drug effect to ensure effective pharmacotherapy.

Propofol Potentiates Phenylephrine-induced Contraction via  Cyclooxygenase Inhibition in Pulmonary Artery Smooth Muscle

2001 ◽  
Vol 94 (5) ◽  
pp. 833-839 ◽  
Author(s):  
Koji Ogawa ◽  
Satoru Tanaka ◽  
Paul A. Murray
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
In Vitro Study ◽  
Isometric Tension ◽  
Relaxation Response ◽  
Response Curves ◽  
Independent Manner ◽  
Pulmonary Arterial

Background The authors previously demonstrated in vivo that the pulmonary vasoconstrictor response to the a agonist phenylephrine is potentiated during propofol anesthesia compared with the conscious state. The current in vitro study tested the hypothesis that propofol potentiates phenylephrine-induced contraction by inhibiting the synthesis and/or activity of vasodilator metabolites of the cyclooxygenase pathway. Methods Canine pulmonary arterial rings were suspended for isometric tension recording. Intracellular calcium concentration ([Ca2+]i) was measured in pulmonary arterial strips loaded with acetoxylmethyl ester of fura-2. After phenylephrine-induced contraction, propofol (10(-7) to 10(-4) M) was administered in the presence or absence of the cyclooxygenase inhibitor ibuprofen (10(-5) M). The effects of propofol on the arachidonic acid and prostacyclin relaxation-response curves were assessed. The amount of 6-keto prostaglandin F1alpha (stable metabolite of prostacyclin) released from pulmonary vascular smooth muscle in response to phenylephrine was measured with enzyme immunoassay in the presence or absence of propofol and ibuprofen. Results Propofol potentiated phenylephrine-induced contraction in pulmonary arterial rings in a concentration-dependent and endothelium-independent manner. In endothelium-denuded strips, propofol (10(-4) M) increased tension by 53+/-11%, and increased [Ca2+]i by 56+/-9%. Ibuprofen also potentiated phenylephrine-induced contraction but abolished the propofol-induced increases in tension and [Ca2+]i. Propofol had no effect on the relaxation response to prostacyclin, whereas propofol and ibuprofen attenuated the relaxation response to arachidonic acid to a similar extent. Phenylephrine markedly increased 6-keto prostaglandin F1alpha production, and this effect was virtually abolished by propofol and ibuprofen. Conclusion These results suggest that propofol potentiates alpha-adrenoreceptor-mediated pulmonary vasoconstriction by inhibiting the concomitant production of prostacyclin by cyclooxygenase.

Modulation by Dipyridamole of the Arachidonic Acid Metabolic Pathway in Platelets an in vivo and in vitro Study

1979 ◽  
Author(s):  
Neri G.G. Serneri ◽  
G. F. Gensini ◽  
R. Abbate ◽  
S. Favilla ◽  
R. Laureano
Keyword(s):  
Arachidonic Acid ◽  
Antiplatelet Agent ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Oral Route ◽  
Radiometric Assay ◽  
Venous Infusion ◽  
Clinical Conditions

Dipyridamole is a useful antiplatelet agent in specific clinical conditions, but its effects on TxEL production by platelets are now being debated, Resting platelets from patients with 1.5-2 fig/ml serum dipyridamole (spectrofluorimetric assay). administered by venous infusion or by oral route, showed an increased concentration (m.v. +60% P<0.001) of cAMP (radiometric assay). After stimulation with thrombin (5U/ml) platelets produced a significantly decreased amount of TxB(m.v. -60%, F< 0.001) (radioimmunoassay with antibody kindly supplied by Doctor J.B. Smith, Philadelphia). However also after stimulation with arachidonic acid (A.A.) 1 mM TxB production was decreased(m.v. -50%, P<0.001). The incubation of control platelets with different concentrations of dipyridamole (0.5, 1 and 2 μg/ml) for 20 min at 37°C resulted in an increase of cAMP and in a decrease of TxB, production after stimulation with thrombin and with A.A.. These results indicate that dipyridamole is endowed with direct antiaggrega= ting activity caused by a decreased production of TxB2. This in tum seems due to an inhibitory modulating effect of cAMP on arachidonic acid cyclo-oxygenation. However our findings do not rule out an inhibitory effect also on phospholipase A2.

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.

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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