摘要:

The effect of inhalation exposure of various biological agents associated with organic dusts on the function of guinea pigs pulmonary phagocytes was investigated. Agents included antigens of Erwinia herbicola, Thermoactinomyces vulgaris, and Aspergillus fumigatus; endotoxin of Erwinia herbicola; bacterial protease; and a fungal glucan preparation. Pulmonary parameters monitored in this study were cellular differential counts from bronchoalveolar lavage, and superoxide anion and or hydrogen peroxide production by phagocytic cells. Most of the agents caused an influx of neutrophils, lymphocytes, and red blood cells to the lung, and an enhancement of secretion of reactive oxygen species by pulmonary phagocytes. However, the relative magnitude of the inflammatory response varied greatly among these biological agents. In general, antigens of Erwinia herbicola and Aspergillus fumigatus were most potent, while bacterial protease was least effective.

ISSN:1528-7394    

DOI:10.1080/009841098159439

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Styrene is a widely used chemical that causes both liver and lung damage in mice. Strain and sex differences in susceptibility to styrene-induced toxicity have been reported. Understanding the relationship of the metabolism of styrene to its toxicity depends upon knowing the balance between the bioactivation of styrene to the epoxide by cytochromes P-450 and the detoxication of the oxide to the glycol by microsomal epoxide hydrolase. When hepatic and pulmonary microsomal preparations from non-Swiss albino (NSA) and Swiss (CD-1) mice were compared for their abilities to metabolize racemic, S - and R -styrene oxide to styrene glycol, enzymic activities were higher in liver than in lung. R -Styrene glycol formation was favored with racemic styrene oxide as the substrate. Only minor strain differences were found that could not account for the differences in reported susceptibility to styrene-induced toxicity. While the oxidation of styrene to styrene oxide was similar in male and female NSA mice, male hepatic microsomes were more active in the metabolism of the oxide to the glycol. Hepatic metabolism of styrene oxide to styrene glycol was inducible by butylated hydroxyanisole, whereas pulmonary metabolism was not. The data indicate that strain differences in susceptibility cannot be accounted for by this detoxication step, and there are sex differences in this reaction.

ISSN:1528-7394    

DOI:10.1080/009841098159448

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

In the present study, it was confirmed that in vivo exposure of rats to silica significantly increases nitric oxide (NO) production by bronchoalveolar lavage cells (BALC), a population of cells that includes alveolar macrophages. Possible mechanisms whereby NO production could be upregulated by rat alveolar macrophages following silica exposure were examined to determine if there is a direct effect of silica on alveolar macrophage NO production or if other factors are involved. BALC were obtained from normal male rats and cultured for 2 h. Nonadherent cells were then removed and the enriched alveolar macrophage cell populations were exposed to test agents for 18-20 h. Media nitrate and nitrite (NOx) concentrations were used to assess NO production and, in some cases, inducible NO synthase mRNA levels were indexed. In vitro exposure to silica (0.1-100 mug ml) had no significant effect on basal NO levels. Furthermore, NO generation was not additionally increased above levels induced by interferon gamma (IFN), lipopolysaccharide (LPS), or other cytokines during simultaneous incubations with silica and IFN, a 2-h pretreatment with silica followed by IFN, or preincubation with IFN, LPS, and or other cytokines before the addition of silica. To evaluate whether cell-cell interactions might be required for the induction of NO production d uring silica challenge, alveolar macrophages were cultured with splenic lymphocytes or blood-derived polymorphonuclear leukocytes. Coculture of splenic lymphocytes with alveolar macrophages resulted in media NOx levels that were greater than the additive levels from each cell type. However, the presence of silica was without additional effect on NO production by either of these cell types. Furthermore, it was found that conditioned media, derived from adherent BALC following silica treatment in vivo, could induce NO production by naive alveolar macrophages. In summary, the collective results from these experiments suggest that cell-cell communication factors, involving the interaction of pneumocytes following in vivo silica exposure, are necessary for the induction of NO by alveolar macrophages.

ISSN:1528-7394    

DOI:10.1080/009841098159457

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Male and female rats and rabbits were used in this study to investigate the acute and subchronic toxicity of a new antismoking (A.S.) mouthwash (0.5 silver nitrate as the active ingredient). The LD50 values for ip administration in male and female rats were 35.7 and 37.2 mg kg body weight, respectively. The corresponding values in male and female rabbits were 113 and 128 mg kg body weight, respectively. The oral LD50 values of the mouthwash in male and female rats were 428 and 433 mg kg body weight, respectively. The corresponding values in male and female rabbits were 1261 and 1320 mg kg body weight, respectively. Postmortem and histopathological examination revealed congestion, edema, hemorrhage, and mucosal necrosis with brown pigment deposition in the upper gastrointestinal and respiratory tracts for the orally treated animals and ascitis, peritoneal fat necrosis, and pigment deposition in ip administered animals. Subchronic toxicity involved administration of low (1.5 mg kg), intermediate (15 mg kg) , and high (150 mg kg) doses of A.S. mouthwash by swabbing the oral cavity daily for 30 consecutive days. Body weight, hematologic observations, and histopathological examination showed no significant differences between control and treated animals, except for dark coloration in teeth and increased platelet counts in treated rats.

ISSN:1528-7394    

DOI:10.1080/009841098159466

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

In the present study we describe changes in aorta at the protein level associated with allylamine (AA) and-aminopropionitrile ( APN) induced vascular toxicity in a rat model. This model represents a remarkable synergistic, necrotizing toxic effect of these combined toxins, and our rationale was to examine protein expression in order to shed light on the mechanisms underlying this synergism. Rats were given AA (100 mg kg body weight day) and APN (1 g kg body weight day) by gavage for 10 d; this protocol has been shown to result in smooth-muscle necrosis, but no visible connective tissue changes. Soluble and insoluble fractions from AA APN- or from APN-treated aorta showed enhanced expression of three high-molecular-weight protein bands (ranges between approximately 120 and 95 kD). The time course of induction of proteins showed the appearance of AA APN-induced specific proteins at d 3 of AA APN treatment. Partial purification and characterization suggested that AA APN specific proteins are likely to be collagen proteins (type I). Thus, the data presented in this article help in understanding the vascular toxicity induced by AA APN or by APN, in that we have described an altered phenotypic expression of collagenous proteins indicative of selective medial vascular toxicity.

ISSN:1528-7394    

DOI:10.1080/009841098159475

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor