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 ◽  
...  

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.

2000 ◽  
Vol 19 (2) ◽  
pp. 69-83 ◽  
Author(s):  
William J. Brock ◽  
David P. Kelly ◽  
Susan M. Munley ◽  
Karin S. Bentley ◽  
Kathy M. McGown ◽  
...  

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.


2021 ◽  
Author(s):  
Fariborz Nowzari ◽  
Farhad Rahmanifar ◽  
Nader Tanideh ◽  
Mohammad Reza Dorvash ◽  
Arezoo Khoradmehr ◽  
...  

Abstract Effects of cottonseed flour in male and female rats’ fertility based on hormonal and histomorphometry changes were studied. Sixty-four Sprague-Dawley adult male and female rats were randomly divided into control and treatment groups. Treatment group was received diets containing cottonseed flour for 35 days. Control group was given standard rat food. Body and testis weights, epididymis semen evaluation indices and serum sex steroid hormones were determined. Histomorphometry alterations of testes and ovary were evaluated. Then, normal female and male rats were mated by rats in both groups and after 35 days, number of pups was measured. However, there was no significant difference in whole body and testes weights, sperm concentration and viability between the control and treatment groups, respectively. Moreover, sperm motility in the treatment rats was significantly lower than the control group. Serum hormones alterations were not significant, but histomorphometry evaluations of testes showed significant changes in the testis structures after chronic consumption of cottonseed flour. In the female rats, body weight did not have significant difference between the treatment and control groups. Histomorphometry data in female ovary showed significant reduction of primary follicle volume and number in the treatment group against control. Follicle stimulating hormone showed insignificant reduction in the treatment group. Number of pups was significantly reduced in the female rats fed by cottonseed flour. Cottonseed flour in rat diet had adverse effects on rat reproduction. Therefore, it can be used as an efficient product for control of the rat population as a natural rodenticide agent.


2020 ◽  
Vol 11 (2) ◽  
pp. 8780-8803

Bisphenol A (BPA) which considered synthetic estrogen that is an essential component of many plastic industries. This research was done to see the impacts of exposure of BPA on reproductive organs and hormonal levels in male and female albino Sprague-Dawley rats. The protective effect of rose water and clove oil on BPA was investigated. Ninety rats were divided into 18 groups, 9 groups of males and they are like for females. Rats were exposed to different oral gavage route 3 times a week by doses of BPA (20 µg, 20 mg, 200 mg) /kg b.wt for 6 weeks and BPA was solubilized in corn oil. BPA induced a significant decrease in total and free testosterone in male rats, in contrast to a significant increase in thyroid-stimulating hormone (TSH), progesterone, estrogen (E2), and prolactin (PRL), while a decrease in Follicle-stimulating hormone (FSH) compared to control groups. Histopathological examination revealed that rosewater and clove oil reduced testes and ovary damages induced by BPA. Rosewater and clove oil components were scanned using GC/MS, which showed that rosewater and clove oil contains phenols, flavonoids, and these inevitably confirm that a prominent role in preventing the damage during treatment. Results indicated that the used doses of BPA disrupted the sex hormone levels in both male and female rats caused reproductive impaired. The chemical and histopathological analysis results indicated that clove oil and rose water improved the adverse effect of BPA. Rosewater and clove oil improved the changes which were stimulated by BPA.


2019 ◽  
Vol 35 (3) ◽  
pp. 204-210

Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-133mzz-E) is an odorless gas that finds uses as a foam transfer agent, heat transfer fluid, and specialty gas. The acute 4-h LC50 (in rats) for HFO-133mzz-E is > 17,000 ppm; it was not an eye or dermal irritant in 3- and 13-week repeated-dose inhalation studies in rats at concentrations up to 1.5% (15,000 ppm). HFO-133mzz-E was not a cardiac sensitizer at 70,000 ppm in a standard epinephrine challenge study in Beagle dogs. In a 3-week, repeated-dose (non-GLP) inhalation range-finding study in male and female rats, HFO-133mzz-E concentrations of 7500 and 15,000 ppm were determined to be well-tolerated. In the follow-up, GLP-compliant, 28-day repeated-dose inhalation study (as per OECD 412), male and female rats were exposed to 0, 1000, 10,000, or 15,000/20,000 ppm (20,000 ppm concentration was decreased to 15,000 ppm after week 1 because of deaths and body weight loss). The study no-observed-adverse-effect level (NOAEL) was established at 10,000 ppm based on reduced body weight gain and mortality observed at 15,000 ppm. In a 90-day GLP-compliant repeated-dose study (as per OECD 413), male and female rats were exposed to 0, 1000, 5000, 7500, or 15,000 ppm HFO-133mzz-E. Three male rats exposed to 15,000 ppm HFO-133mzz-E died during exposure; clinical signs such as restlessness, blepharospasm, and myoclonic jerks were also observed, during the first month of the study, at 15,000 ppm. There were no significant gross or histopathological organ/tissue lesions attributable to HFO-133mzz-E exposure. The study NOAEL was established at 7500 ppm. In a GLP prenatal developmental study (OECD 414), groups of time-mated nulliparous female rats were exposed via inhalation to 0, 1000, 5000, 7500, or 15,000 ppm HFO-1336mzz-E beginning on gestation day (GD) 6 up to and including GD 19. Under the conditions of this study, the NOAEL for maternal and fetal effects was established at 7500 ppm. HFO-1336mzz-E was not genotoxic in either in vitro or in vivo assays. Based on the results of the 90-day inhalation study, 7500 ppm was determined to be the NOAEL and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 400 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-E.


Author(s):  
Lynda AÏNOUZ ◽  
Mohamed ZAOUANI ◽  
Hayat REMICHI ◽  
Sofiane BOUDJELLABA ◽  
Kahina CHABANE ◽  
...  

Cardiovascular disease (CVD) are mainly consequent of atherosclerosis.  Men develop CVD at a young age, this risk increases in women at an older age. Several studies have been carried out on male rats, but experiments on growing rats especially female are rare.  The objective of this study was to investigate the effect of a high cholesterol and high fructose diet on the coronary artery and myocardium in growing male and female rats Young Wistar rats were divided into control groups fed a standard diet, cholesterol groups supplemented with 3% cholesterol (ChD), and cholesterol-fructose groups supplemented with 3% cholesterol and 15% fructose (ChFrD) for 14 weeks. Each group consists of male (n=6) and female (n=6) rats.   We found, in comparison with corresponding controls rats, that both ChD and ChFrD diets caused a significant hyperglycemia and dyslipidaemia. In hearts supernatants, we highlighted increases of total lipids, malondialdehyde and Catalase assays. The histopathological examination showed a disorganization of the myocardial structure, arterial walls damage and endothelium injuries. Our study showed that ChD and ChFrD diets, caused weight, biochemical, oxidative and tissue disturbances that could lead to CVD in both young male and female Wistar rats even during the growing period.


Toxics ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 76
Author(s):  
Yeon-Mi Lim ◽  
Haewon Kim ◽  
Seong Kwang Lim ◽  
Jean Yoo ◽  
Ji-Young Lee ◽  
...  

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.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.


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