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.

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

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.

Evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract

2017 ◽  
Vol 37 (7) ◽  
pp. 725-741 ◽  
Author(s):  
A Nagatomo ◽  
M Oguri ◽  
N Nishida ◽  
M Ogawa ◽  
A Ichikawa ◽  
...  
Keyword(s):  
Oral Dose ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Ethanol Extract ◽  
Female Rats ◽  
Toxicity Studies ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Rose Hip

Rose hip is the fruit of the rose plant, which is widely used in food, cosmetics and as a traditional medicine. Therefore, rose hip is considered safe and has a sufficient history of consumption as food. However, few studies have reported on the safety of rose hip extracts in toxicological analyses. Thus, to evaluate the safety of rosehip polyphenol MJ (RHPMJ), an aqueous ethanol extract standardized with the trans-tiliroside content, we performed genotoxicity and 90-day repeated oral dose toxicity studies in compliance with the Organisation for Economic Co-operation and Development-Good Laboratory Practice. RHPMJ did not induce gene mutations in reverse mutation tests of Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA strains and did not induce chromosomal aberrations in cultured Chinese hamster lung (CHL/IU) cells. Moreover, micronucleus tests using rat bone marrow showed RHPMJ had no micronucleus-inducing potential. Finally, 90-day repeated oral dose toxicity studies (100–1000 mg/kg) in male and female rats showed no treatment-related toxicity in rats. These data indicate that the RHPMJ had no genotoxicity and a no-observed-adverse-effect level greater than 1000 mg/kg in rats.

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.

scholarly journals Genotoxicity Evaluation of Propyl-Propane-Thiosulfinate (PTS) from Allium genus Essential Oils by a Combination of Micronucleus and Comet Assays in Rats

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 989
Author(s):  
Antonio Cascajosa-Lira ◽  
María Puerto ◽  
Ana I. Prieto ◽  
Silvia Pichardo ◽  
Leticia Díez-Quijada Jiménez ◽  
...  
Keyword(s):  
Essential Oils ◽  
Oxidative Dna Damage ◽  
Animal Feed ◽  
Female Rats ◽  
Feed Additive ◽  
Histopathological Study ◽  
Male And Female Rats ◽  
Histopathological Studies

Propyl-propanethiosulfinate (PTS) is a component of Allium essential oils. This organosulfur molecule can be used as a feed additive to decrease the appearance of bacterial resistances caused by the residues of antibiotics. In previous in vitro genotoxicity studies, contradictory results were reported for PTS. In this work, the in vivo genotoxicity of PTS in male and female rats was assessed for the first time, following OECD (Organisation for Economic Co-operation and Development) guidelines. After oral administration (doses: 5.5, 17.4, and 55.0 mg/kg PTS body weight), a combination of the micronucleus (MN) assay (OECD 474) in bone marrow and the standard and enzyme-modified comet assay (OECD 489) was performed. After necropsy, histopathological studies were also carried out. The results did not show the in vivo genotoxicity of PTS at any doses assayed, revealed by the absence of increased MN, and DNA strand breaks or oxidative DNA damage in the standard and enzyme-modified comet assays. The histopathological study revealed that only the highest dose tested (55.0 mg/kg) in the liver and all dose groups in the stomach presented minimal pathological lesions in the organs studied. Consequently, the present work confirms that PTS is not genotoxic at the doses assayed, and it is a promising natural alternative to synthetic preservatives and antibiotics in animal feed.

scholarly journals Effects of Funchicórea®, a Traditional Brazilian Herbal Complex, on Intestinal Motility in Healthy and Constipated Rodents

2020 ◽  
pp. 26-36
Author(s):  
Valéria L. Assis ◽  
Ana C. M. F. Veras ◽  
Priscilla M. P. Maciel ◽  
José G. F. Albuquerque ◽  
Carmem Zancanella ◽  
...  
Keyword(s):  
Scientific Data ◽  
Intestinal Transit ◽  
Female Rats ◽  
Control Group ◽  
Male Mice ◽  
Spasmolytic Activity ◽  
Rat Ileum ◽  
Male And Female Rats

Ethnopharmacological Relevance: The traditional herbal medicinal product Funchicórea® has been widely used in clinical practice for the treatment of intestinal colic and constipation in newborns. However, no scientific data on the herbal product to prove its efficacy is available. Aim of the Study: This study aimed to evaluate the laxative and spasmolytic actions of Funchicórea®. Materials and Methods: Wistar rats (Rattus norvegicus) and Swiss mice (Mus musculus) of both sex, were used. In vivo pharmacological assays were performed to evaluate the stimulating effect on the gastrointestinal tract, and in vitro studies to verify its spasmodic activity. Results: Funchicórea® increased the motility of the small intestine in male mice at doses of 100 mg/kg (161.66±14.86 %, n=6) and 200 mg/kg (151.04±17.17 %, n=6) compared to control (100.00±10.49 %, n=6). However, this drug did not induce any change in intestinal transit in female mice. The intestinal transit of male mice treated with loperamide (3 mg/kg/day, during three days) was reduced 66.25±7.49 % (n=8) compared to the control group (100.00±5.16%, n=8) and we observed the normalization of the intestinal transit in constipated animals treated with Funchicórea® 100 mg/Kg (98.42±6.33 %, and 200 mg/kg (99.32±8.47%, n=7). Similar results were observed in the quantification for 24 hours of male and female rats faeces constipated by loperamide (3 mg/kg/day three days), however, in both animals groups treated with Funchicórea® 100 mg/kg (1.24±2.90 g, male; 3.60±0.80 g, female, n=6) and 200 mg/Kg (8.70±2.01 g, male, 10.03±1.30 g, female, n=6) the levels of faeces returned to basal values compared to constipated group (4.01±1.43 g, male; 1.70±0.10 g, female, n=6). In addition, Funchicórea® (0.01-1000 μg/mL) elicited relaxation in rat ileum pre-contracted by KCl 40 mM (Emax=97.5±7.0 %, n=7) and carbachol (1 μM, Emax=100.0±7.0 %, n=7). Conclusion: The results obtained demonstrated that the herbal medicine Funchicórea® acts by stimulating the intestine of rats and mice and has spasmolytic activity in isolated rat ileum.

Sign in / Sign up

Export Citation Format

Share Document