scholarly journals In Vitro and In Vivo Evaluation of the Toxic Effects of Dodecylguanidine Hydrochloride

Toxics ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 76
Author(s):  
Yeon-Mi Lim ◽  
Haewon Kim ◽  
Seong Kwang Lim ◽  
Jean Yoo ◽  
Ji-Young Lee ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Water Soluble ◽  
Female Rats ◽  
Male Rats ◽  
Inhalation Toxicity ◽  
Dependent Manner ◽  
High Exposure ◽  
Inhalation Study

The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC50: 0.39 μg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m3 for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-β1, IL-1β, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC50 of DGH in rats after exposure for 4 h was estimated to be >68 mg/m3. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health.

scholarly journals Inhalation of Talc Induces Infiltration of Macrophages and Upregulation of Manganese Superoxide Dismutase in Rats

2015 ◽  
Vol 34 (6) ◽  
pp. 491-499 ◽  
Author(s):  
Ilseob Shim ◽  
Hyun-mi Kim ◽  
Sangyoung Yang ◽  
Min Choi ◽  
Gyun-baek Seo ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Inhalation Toxicity ◽  
Inhalation Study ◽  
Male And Female ◽  
Male And Female Rats

Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m3 for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m3 of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m3 talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

scholarly journals Sal B Alleviates Myocardial Ischemic Injury by Inhibiting TLR4 and the Priming Phase of NLRP3 Inflammasome

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4416 ◽  
Author(s):  
Yang Hu ◽  
Qingju Li ◽  
Yunzheng Pan ◽  
Li Xu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Troponin I ◽  
Salvia Miltiorrhiza ◽  
Ischemic Injury ◽  
Water Soluble ◽  
Dependent Manner ◽  
Priming Phase ◽  
Myocardial Ischemic Injury

Salvianolic acid B is one of the main water-soluble components of Salvia miltiorrhiza Bge. Many reports have shown that it has significant anti-myocardial ischemia effect. However, the underlying mechanism remains unclear. Our present study demonstrated that Sal B could alleviate myocardial ischemic injury by inhibiting the priming phase of NLRP3 inflammasome. In vivo, serum c-troponin I (cTn), lactate dehydrogenase (LDH) levels, the cardiac function and infract size were examined. We found that Sal B could notably reduce the myocardial ischemic injury caused by ligation of the left anterior descending coronary artery. In vitro, Sal B down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated H9C2 cells. Furthermore, Sal B reduced the expression levels of IL-1β and NLRP3 inflammasome in a dose-dependent manner. In short, our study provided evidence that Sal B could attenuate myocardial ischemic injury via inhibition of TLR4/NF-κB/NLRP3 signaling pathway. And in an upstream level, MD-2 may be the potential target.

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.

Octamethylcyclotetrasiloxane (D4)

2016 ◽  
Vol 33 (1) ◽  
pp. 2-15
Keyword(s):  
Respiratory Tract ◽  
Weighted Average ◽  
Female Reproductive Tract ◽  
Female Rats ◽  
Exposure Level ◽  
Acute Administration ◽  
Upper Respiratory Tract ◽  
Inhalation Study

Octamethylcyclotetrasiloxane (D4; CAS No. 556-67-2) is used as a monomer in the manufacture of polymeric materials, which are widely used in various industrial and/or medical applications, such as breast implants. D4 has a relatively low order of toxicity following acute administration via the oral, dermal, and inhalation routes of exposure and is not considered to be a dermal or eye irritant or to be a dermal sensitizer. There is no appreciable dermal absorption of D4 based on results from in vivo and in vitro studies. D4 has not been shown to be genotoxic/mutagenic when tested in a number of short-term in vitro and in vivo assays. Overall, studies have demonstrated adverse effects on specific female reproductive endpoints at higher exposure concentrations; however, no D4 exposure-specific effects were noted with respect to developmental endpoints. Inhalation exposure of rats to 700 ppm D4 for up to 24 months produced effects in the liver, kidney, and uterus (weight changes, hepatocellular hypertrophy, endometrial hyperplasia, and nephropathy). Changes in the nasal epithelium (eosinophilic globules) were also noted at 150 and 700 ppm. Despite 24 months of exposure, only mild to minimal inflammatory responses were found at 150 ppm, and overall, the basic integrity of the respiratory tract was unchanged at this dose. At 700 ppm, there was an increased incidence of endometrial adenomas in female rats. Based on the adverse changes in the respiratory tract, kidney, and female reproductive tract in the chronic inhalation study, 150 ppm was determined to be the no-observed-adverse-effect level (NOAEL) and was selected as the point of departure for the derivation of the workplace environmental exposure level (WEEL®) value. The inhalation NOAEL was adjusted to account for interindividual variability and residual uncertainty regarding upper respiratory tract changes still occurring at 150 ppm. An 8-h time-weighted average WEEL value of 10 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to airborne D4.

Inhalation Toxicity of High Flash Aromatic Naphtha

1989 ◽  
Vol 5 (3) ◽  
pp. 415-428 ◽  
Author(s):  
David G. Clark ◽  
Steven T. Butterworth ◽  
John G. Martin ◽  
Howell R. Roderick ◽  
Michael G. Bird
Keyword(s):  
Systemic Toxicity ◽  
Female Rats ◽  
Petroleum Distillate ◽  
Low Grade ◽  
Inhalation Toxicity ◽  
High Exposure ◽  
Inhalation Study ◽  
Male And Female Rats ◽  
Liver And Kidney ◽  
Exposure Levels

A petroleum distillate—a high aromatic naphtha—consisting of a 50/50 blended mixture of equivalent products. SHELLSOL A* and SOLVESSO 100**, containing C9 isomers (75 percent)particularly trimethyl benzenes, was examined for systemic toxicity in rats by inhalation exposure. A preliminary 13-week inhalation study with SHELLSOL A had resulted in liver and kidney weight increases in female rats at the high (7400 mg/m3) and medium (3700 mg/m3) exposure levels, and a low grade anaemia in females at all exposure levels (7400, 3700 and 1800 mg/m3). The follow-up 12-month inhalation study in rats described here used atmospheres generated from the SHELLSOL A/SOLVESSO 100 blend of 1800, 900 and 450 mg/m3. Initial reduction in body weight gain occurred in both male and female rats at the higher exposures. Various statistically significant haematological changes were transiently seen in males up to six months, but were not considered biologically significant. High exposure male liver and kidney weights were increased at 6 and 12 months but, in the absence of histopathological changes, were considered to be physiological adaptive responses. No treatment-related histopathological abnormalities were found. It is concluded that chronic exposure to this high aromatic naphtha is without systemic toxicity in rats under the conditions of these studies.

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.

scholarly journals Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen
Keyword(s):  
Postnatal Development ◽  
Estrous Cycle ◽  
Third Ventricle ◽  
Female Rats ◽  
Male Rats ◽  
Relative Distribution ◽  
Gonadotropin Secretion ◽  
Related Peptide

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.

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.

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