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
2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  

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.


1999 ◽  
Vol 18 (2) ◽  
pp. 106-110
Author(s):  
Livia Secondin ◽  
Stefano Maso ◽  
Andrea Trevisan

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.


1963 ◽  
Vol 43 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Julian I. Kitay

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.


2020 ◽  
Author(s):  
Hyoung-Yun Han ◽  
Eunsol Seong ◽  
Mi-Jin Yang ◽  
Cheolho Yoon ◽  
Gwang Hee Lee ◽  
...  

Abstract Background The International Agency for Research on Cancer classified as a Group B carcinogen inhaled titanium dioxide (TiO 2 ) nanoparticles, and France banned the application of TiO 2 nanoparticles as a food additive based on the insufficient oral toxicity data. However, there still remains controversial due to the insufficient evidence for its safety. Here, we explored the toxicity of food-grade TiO 2 nanoparticles (hereafter, E171) in vivo and in vitro . Methods We investigated the subchronic toxic responses of E171 (0, 10, 100, and 1,000 mg/kg) under the Good Laboratory Practice (GLP) system and tried to elucidate the possible toxic mechanism using AGS cells, a human stomach epithelial cell line. Results There were no dose-related changes in the Organization for Economic Co-operation and Development test guideline-related endpoints. Meanwhile, E171 deeply penetrated cells lining the stomach tissues of rats administered the maximum dose, and blood IgM (male and female) and GM-CSF (female) levels were significantly lower in the E171-treated rats than in the control rats. Colonic SOD-1 (male and female) and SOD-2 (female) protein levels decreased with increasing Ti accumulation. When exposed to AGS cells for 24 h, E171 (40 μg/mL) located in the perinuclear region. The E171 treatment affected expression of ER stress-related proteins but did not induce cell death up to the used maximum concentration (40 μg/mL). A gene profile analysis also showed that immune response-related microRNAs were most strongly affected by E171 exposure. Conclusion Considering the potential toxicity observed in vivo and in vitro test, we concluded that the NOAEL of E171 for 90-days repeated oral administrations is less than 1,000 mg/kg for both male and female rats. Additionally, E171 may attenuate host's defense function against foreign bodies by decreasing antioxidant capacity, thus we propose that chronic toxicity studies on E171 are required to warrant the safety for use in the food industry.


Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1902-1913 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
M. Romero ◽  
F. Ruiz-Pino ◽  
...  

Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms of action in the control of gonadotropin secretion in higher vertebrates. Yet, these analyses have so far relied mostly on indirect approaches, while direct assessment of their physiological roles has been hampered by the lack of suitable antagonists. RF9 was recently reported as a selective and potent antagonist of the receptors for RFRP (RFRPR) and the related neuropeptides, neuropeptide FF (NPFF) and neuropeptide AF (NPFF receptor). We show here that RF9 possesses very strong gonadotropin-releasing activities in vivo. Central administration of RF9 evoked a dose-dependent increase of LH and FSH levels in adult male and female rats. Similarly, male and female mice responded to intracerebroventricular injection of RF9 with robust LH secretory bursts. In rats, administration of RF9 further augmented the gonadotropin-releasing effects of kisspeptin, and its stimulatory effects were detected despite the prevailing suppression of gonadotropin secretion by testosterone or estradiol. In fact, blockade of estrogen receptor-α partially attenuated gonadotropin responses to RF9. Finally, systemic administration of RF9 modestly stimulated LH secretion in vivo, although no direct effects in terms of gonadotropin secretion were detected at the pituitary in vitro. Altogether, these data are the first to disclose the potent gonadotropin-releasing activity of RF9, a selective antagonist of RFRP (and NPFF) receptors. Our findings support a putative role of the RFRP/gonadotropin-inhibitory hormone system in the central control of gonadotropin secretion in mammals and have interesting implications concerning the potential therapeutic indications and pharmacological effects of RF9.


1986 ◽  
Vol 8 (1-4) ◽  
pp. 267-278 ◽  
Author(s):  
Karel L. M. Lavrijsen ◽  
Willem Meuldermans ◽  
Fons A. G. Knaeps ◽  
William Lauwers ◽  
Jozef Heykants

1982 ◽  
Vol 17 (6) ◽  
pp. 703-706 ◽  
Author(s):  
Paul Andersson ◽  
Ralph Brattsand ◽  
Staffan Edsbäcker ◽  
Leif Källström ◽  
Åke Ryrfeldt

1970 ◽  
Vol 48 (12) ◽  
pp. 829-831 ◽  
Author(s):  
J.-G. Alary ◽  
J. Brodeur

A study was undertaken to investigate a possible correlation between the acute LD50 of parathion, in weanling and adult male and female rats, and the activity of the liver enzymes involved in the in vitro metabolism of parathion and its toxic oxygen analogue, paraoxon. A close relationship was found in adult male and female rats, as well as in adult females pretreated with phenobarbital, between the LD50 and the rate of in vitro degradation of parathion by the liver under experimental conditions in which both oxidative and hydrolytic metabolism occur. On the same basis, immature rats appeared to be more sensitive to parathion than was to be expected from the ability of their livers to metabolize parathion in vitro. It is concluded that the rate of in vitro degradation of parathion by the liver is a satisfactory index of the in vivo toxicity of parathion in adult rats, but not in immature animals.


2021 ◽  
Author(s):  
Latha Damle ◽  
Hrishikesh Damle ◽  
Shiban Ganju ◽  
C Chandrashekar ◽  
BR Bharath

AbstractBackgroundIn the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation.PurposeTo screen the phytochemicals for Anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo.MethodThe phytochemicals for Anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of plant extracts of Z. piperitum (ATRI-CoV-E1), W. somnifera (ATRI-CoV-E2), C. inophyllum (ATRI-CoV-E3), A. paniculata (ATRI-CoV-E4), and C. Asiatica (ATRI-CoV-E5). The in vitro safety and anti-SARS-CoV-2 activity of plant extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats.ResultsThe percentage of cell viability for ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for ATRI-COV-E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 µM and 0.11 µM respectively, For E gene and N gene, ATRI-CoV-E4 showed IC50 of 1.18 µg and 1.16 µg respectively. Taking the clue from in vitro findings, the plant extracts A. paniculata (ATRI-COV-E4), W. somnifera extract (ATRI-COV-E5) and C. asiatica extract (ATRI-COV-E2) were combined (ATRICOV 452) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed.ConclusionThe study demonstrated the Anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.


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