The Experimental Study of Cardiotoxic Effects of Lead Oxide Nanoparticles by Their Various Routes of Exposure

Author(s):  
Minigalieva IA ◽  
MP Sutunkova ◽  
SV Klinova ◽  
SN Solovyova ◽  
LI Privalova ◽  
...  

Background: Lead oxide nanoparticles are emitted in the workplace air of copper smelters. They are also a by-product in many other metallurgical industries. Objectives: Adverse health effects of lead oxide nanoparticles (PbO-NPs) were assessed in vivo using various routes of exposure with special attention paid to particle cardiotoxicity. Materials and methods: The subacute inhalation experiments were conducted on outbred female rats exposed to the generated aerosol of PbO-NPs in the concentration of 1.30 ± 0.10 mg/m3, 4 hours a day during five consecutive days, using the Nose-Only Inhalation Exposure System. The study of subchronic exposure to PbO-NPs was conducted on male rats using intraperitoneal injections made thrice a week during six weeks (18 injections in total). Conclusions: Following both types of exposure to PbO-NPs, we observed changes in toxicological indices including those specific for lead including a decrease in hemoglobin counts, an increase in blood reticulocyte counts and urine concentrations of δ-aminolevulenic acid. The subacute inhalation exposure to PbO-NPs affected electrocardiographic findings in animals (an increase in amplitudes of P and T waves) while the subchronic intraperitoneal injections decreased blood pressure and changed biochemical indices of the cardiovascular system (decreased activity of the angiotensin-converting enzyme and the concentration of endodelin-1).

Author(s):  
Arnold Gutierrez ◽  
Kevin M. Creehan ◽  
Michael A. Taffe

AbstractBackgroundThe ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.ResultsInhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups.ConclusionsThis work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.


Author(s):  
M. Р. Sutunkova ◽  
S. N. Solovyeva ◽  
I. N. Chernyshov ◽  
S. V. Klinova ◽  
V. B. Gurvich ◽  
...  

Outbred white female rats were exposed to an aerosol of lead oxide nanoparticles in a nose-only inhalation setup at an average concentration of 1.30 ± 0.10 mg / m3 during 5 days for 4 hours a day. In parallel, the control group of rats was subjected to sham exposure under similar conditions. The deposition of nanoparticles in the lungs and in the olfactory region of the brain was detected using transmission electron microscopy. Some disorders of the body state were detected in the exposed group, some of which can be considered as the result of a lead-specific toxic effect (an increase in the proportion of reticulocytes and in urinary excretion of δ-aminolevulinic acid), and others - the result of nanoparticles circumventing the blood-brain barrier (axon demyelination, vacuolization of the neurons’ cytoplasm).


1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner

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)


Toxicology ◽  
2017 ◽  
Vol 380 ◽  
pp. 72-93 ◽  
Author(s):  
Ilzira A. Minigalieva ◽  
Boris A. Katsnelson ◽  
Vladimir G. Panov ◽  
Larisa I. Privalova ◽  
Anatoly N. Varaksin ◽  
...  

2018 ◽  
Vol 96 (8) ◽  
pp. 882-887 ◽  
Author(s):  
Chao Yin ◽  
Guofu Wang ◽  
Shixing Gao ◽  
Yanping Huang ◽  
Ruqian Zhao ◽  
...  

This study evaluated the effect of maternal restraint stress during the gestation period on behaviors, biochemical parameters, and antioxidant capacities of offspring rats (Rattus norvegicus (Berkenhout,1769)) at weaning age. Behaviors, plasma biochemical indices, and antioxidant ability of the liver, soleus muscle, and gastrocnemius muscle of mother and (or) offspring rats were analyzed. Significant increases were found in the immobility and swinging behavior frequencies of offspring male rats; no difference was found in behaviors of female rats. The antioxidant indices including superoxide dismutase, nitric oxide synthase, and total antioxidant capacity in the soleus muscle of offspring male rats were significantly decreased in the restraint group. Female offspring rats showed significant lower glutathione and higher malondialdehyde levels in the gastrocnemius muscle and liver, respectively. No difference was found in the productive performance and plasma biochemical indices of maternal rats, nor in the biochemical parameters of the two groups of weaning rats. The results suggested that maternal chronic stresses negatively affected the behaviors and antioxidant abilities of offspring rats, and that these effects possibly have a greater impact on offspring male rats than on female rats.


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.


1994 ◽  
Vol 76 (3) ◽  
pp. 1172-1175 ◽  
Author(s):  
A. Ferry ◽  
C. Le Page ◽  
M. Rieu

The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45–120 min/day and 15–30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.


Author(s):  
Jana Tulinska ◽  
Zora Krivošíková ◽  
Aurelia Liskova ◽  
Miroslava Lehotska Mikusova ◽  
Vlasta Masanova ◽  
...  

Due to widespread use in various industrial processes, the risk of inhalation exposure to lead oxide nanoparticles (PbO NPs) is growing and limited information evokes the need for hazard assessment...


Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen

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.


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.


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