scholarly journals Assessment of the Toxicity and Carcinogenicity of Double-Walled Carbon Nanotubes in the Rat Lung After Intratracheal Instillation: A Two-Year Study

2021 ◽  
Author(s):  
David Bedell Alexander ◽  
Dina Mourad Saleh ◽  
Shengyong Luo ◽  
Omnia Hosny Mohamed Ahmed ◽  
William T. Alexander ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Lung Tumor ◽  
Industrial Applications ◽  
Vehicle Control ◽  
Control Group ◽  
Rat Lung ◽  
Vehicle Control Group ◽  
Double Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

Abstract Background Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure. Methods Rats were divided into six groups: Untreated, Vehicle, 3 DWCNT groups (0.12mg/rat, 0.25mg/rat and 0.5mg/rat), and MWCNT-7 (0.5mg/rat). The test materials were administrated by intratracheal - intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice at weeks 52 and 104. Results DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. Conclusions Our results demonstrate that DWCNTs are biopersistent in the rat lung and induce chronic inflammation. Moreover, rats treated with 0.5 mg DWCNT developed pleural fibrosis. While our results do not show that DWCNT is carcinogenic in the rat lung, total tumor incidence was significantly increased in the 0.5 mg DWCNT group. Taken together, these findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and carcinogenic cannot be ignored.

scholarly journals In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens

2021 ◽  
Author(s):  
Nicholas P. Clayton ◽  
Akash Jain ◽  
Stephanie A. Halasohoris ◽  
Lisa M. Pysz ◽  
Sanae Lembirik ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Vehicle Control ◽  
Control Group ◽  
Post Challenge ◽  
Vehicle Control Group ◽  
Tebipenem Pivoxil

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 – 0.008 μg/ml for B. anthracis, ≤0.0005 – 0.03 μg/ml for Y. pestis, 0.25 – 1 μg/ml for B. mallei, and 1 – 4 μg/ml for B. pseudomallei. In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

scholarly journals Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity.

1997 ◽  
Vol 41 (8) ◽  
pp. 1738-1742 ◽  
Author(s):  
D A Steinberg ◽  
M A Hurst ◽  
C A Fujii ◽  
A H Kung ◽  
J F Ho ◽  
...  
Keyword(s):  
Serial Passage ◽  
Vehicle Control ◽  
Control Group ◽  
Vehicle Control Group ◽  
Mueller Hinton ◽  
Immunocompetent Mice ◽  
Systemic Infections ◽  
Mueller Hinton Broth

Protegrin-1 (PG-1) is a cysteine-rich, 18-residue beta-sheet peptide isolated from porcine leukocytes with antimicrobial activity against a broad range of microorganisms. The MICs of PG-1 against representative gram-positive and gram-negative bacteria ranged from 0.12 to 2 microg/ml. At these levels, PG-1 was rapidly bactericidal in vitro, reducing the number of viable CFU of either methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa by more than three log units in less than 15 min. Resistance to PG-1 did not develop after 11 subculturings of P. aeruginosa or 18 subcultures of MRSA in Mueller-Hinton broth containing PG-1 at one-half the MIC. Under similar conditions of serial passage, the MICs of norfloxacin and gentamicin against P. aeruginosa increased 10 and 190 times, respectively. Similarly, the MIC of norfloxacin against MRSA increased 85 times. Immunocompetent mice inoculated intraperitoneally (i.p.) with P. aeruginosa or S. aureus exhibited 93 to 100% mortality in the vehicle control group compared with 0 to 27% mortality in animals that received a single i.p. injection of PG-1 (0.5 mg/kg of body weight). Mice inoculated with S. aureus by intravenous (i.v.) injection and dosed 0 to 60 min later with a single i.v. injection of PG-1 (5 mg/kg) had a mortality of 7 to 33%, compared to a mortality of 73 to 93% in the vehicle controls. In leukopenic mice inoculated i.v. with vancomycin-resistant Enterococcus faecium, mortality was 87% in the vehicle control group and 33% in animals that received a single i.v. injection of PG-1 (2.5 mg/kg). Taken together, these data indicate that PG-1 has potential for use as an antimicrobial agent in the treatment of local or systemic infections caused by clinically relevant pathogens.

Nifedipine inhibits adrenal but not circulating catecholamine response to nicotinic stimulation in dogs

1994 ◽  
Vol 267 (6) ◽  
pp. R1545-R1551 ◽  
Author(s):  
R. Gaspo ◽  
N. Yamaguchi ◽  
J. de Champlain
Keyword(s):  
High Performance ◽  
Vehicle Control ◽  
Control Group ◽  
Vehicle Control Group ◽  
Aortic Blood ◽  
Catecholamine Response ◽  
Ca2 Channels ◽  
Sodium Plasma ◽  
Catecholamine Concentration

We investigated whether dihydropyridine-sensitive L-type Ca2+ channels are implicated in adrenal and sympathetic neural catecholamine release in response to nicotinic stimulation by 1,1-dimethyl-4-phenylpiperazinium (DMPP), a selective cholinergic nicotinic agonist, in dogs anesthetized with pentobarbital sodium. Plasma epinephrine and norepinephrine concentrations were measured in adrenal venous and aortic blood by a high-performance liquid chromatography-electrochemical method. In the vehicle control group, intravenous injection of DMPP (15 micrograms/kg iv) produced a significant increase in adrenal venous catecholamine output and aortic catecholamine concentration. These increasing responses were highly reproducible on the repetition of DMPP injection given 30 min after the first injection. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine and norepinephrine output in response to DMPP was attenuated by 42% (P < 0.05), while no significant changes were observed in the aortic catecholamine response to DMPP. In dogs treated with pentolinium (1 mg/kg iv), both adrenal epinephrine and norepinephrine responses to DMPP were inhibited by 67% (P < 0.05) and 84% (P < 0.05), respectively. Furthermore, pentolinium inhibited aortic catecholamine response to DMPP by > 95% (P < 0.05). The present study suggests that DMPP-induced release of adrenal catecholamines was mediated, at least in part, through mechanisms involving dihydropyridine-sensitive L-type Ca2+ channels under in vivo conditions. By contrast, however, the results also suggest that dihydropyridine-sensitive L-type Ca2+ channels were not implicated in the neurotransmission at the level of sympathetic ganglions.

Double-walled carbon nanotubes synthesized using carbon black as the dot carbon source

2006 ◽  
Vol 17 (13) ◽  
pp. 3100-3104 ◽  
Author(s):  
Zhi-Gang Chen ◽  
Feng Li ◽  
Wen-Cai Ren ◽  
Hongtao Cong ◽  
Chang Liu ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Carbon Source ◽  
Carbon Black ◽  
Double Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice

2014 ◽  
Vol 32 (7) ◽  
pp. 1293-1301 ◽  
Author(s):  
Saeed Ivani ◽  
Isaac Karimi ◽  
Seyed Reza Fatemi Tabatabaei ◽  
Leila Syedmoradi
Keyword(s):  
Carbon Nanotubes ◽  
Prenatal Exposure ◽  
Motor Development ◽  
Behavioral Changes ◽  
Single Wall Carbon Nanotubes ◽  
Control Group ◽  
Plus Maze ◽  
Righting Reflex ◽  
Novel Drug ◽  
Walled Carbon Nanotubes

Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups ( n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation.

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