Neonatal rat age, sex and strain modify acute antioxidant response to ozone

Dye, Janice A.; Gibbs-Flournoy, Eugene A.; Richards, Judy H.; Norwood, Joel; Kraft, Katherine; Hatch, Gary E.

doi:10.1080/08958378.2017.1369602

Cited by 7 publications

(5 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though no difference in the survival rate of the FA-exposed GxM and E 2 mice and the GxF and CoP mice was observed, the reduced survival in response to O 3 exposure of the GxM and E 2 mice vs that of the GxF and CoP SP-A KO mice indicated the detrimental effect of estrogen on survival if infection is preceded by ozone exposure. This observation was in line with previous animal and human studies showing severe respiratory diseases in females exposed to air pollution and oxidative stress compared to males [4,5,[29][30][31]62,63].…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, an animal model of LPS-induced sepsis showed increased total leukocyte, polymorphonuclear cell, and TNF-α levels in bronchoalveolar lavage (BAL) fluid, as well as greater airway hyper-responsiveness in males compared to females [28]. In contrast, the prior exposure of infected animals to ozone has been shown to increase the susceptibility of females to respiratory diseases compared to males [4,5,[29][30][31]. Moreover, in line with human studies, previous studies have demonstrated the decreased survival of both SP-A KO and wild type male mice compared to females after K. pneumoniae infection, but the survival pattern reversed following the prior exposure of ozone [4,5].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

et al. 2020

View full text Add to dashboard Cite

Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O3) and sex, as well as gonadal hormones, on the bronchoalveolar lavage (BAL) readouts and survival, respectively, of Klebsiella pneumoniae-infected SP-A KO mice. Male and female SP-A KO mice were exposed to O3 or filtered air and infected with K. pneumoniae. We studied markers of inflammation and tissue damage at 4, 24, and 48 h, as well as the survival over 14 days, of gonadectomized (Gx) mice implanted with control pellets (CoP) or hormone (5α-dihydrotestosterone (DHT) in female gonadectomized mice (GxF) or 17β-estradiol (E2) in male gonadectomized mice (GxM)). We observed: (1) an increase in neutrophil and macrophage inflammatory protein-2 levels as time progressed post-infection, and O3 exposure appeared to increase this response; (2) an increase in lactate dehydrogenase, total protein, oxidized protein, and phospholipids in response to O3 with no consistent sex differences in studied parameters; and (3) a reduction in survival of the GxM and CoP mice, the GxM and E2 mice, and the GxF and DHT mice but not for the GxF and CoP mice after O3. Without SP-A, (a) sex was found to have a minimal impact on BAL cellular composition and tissue damage markers, and (b) the impact of gonadal hormones on survival was found to involve different mechanisms than in the presence of SP-A.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Lung oxidative stress, DNA damage and methylation alterations are transient events that can be impacted by susceptibilities including age, sex, underlying disease, and species. We have previously reported differences in the antioxidant response to ozone in between strains of rats (Hatch et al 2015;Dye et al 2017). While Long-Evans rats were not included in the aforementioned strain comparisons, the male, Long-Evans rat appears sensitive to the pulmonary damage and epigenetic changes following exposure to ozone.…”

Section: Discussionmentioning

confidence: 99%

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Miller

Dye

Schladweiler

et al. 2018

Inhalation Toxicology

Self Cite

View full text Add to dashboard Cite

Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0 ppm ozone for 4 h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.

show abstract

“…In toxicity testing, the neonatal life stage refers to the period from birth to 3 weeks of age ( 15 ), but the definition is debatable because newborn rodents are very immature due to the short gestation period, and some researchers suggest they better resemble human preterm infants ( 16 ). A similar definition has been used for rats ( 17 ). Thus, this review will focus on rodent models supplemented with soy isoflavones within this period.…”

Section: Animal Modelsmentioning

confidence: 99%

Skeletal Effects of Early-Life Exposure to Soy Isoflavones—A Review of Evidence From Rodent Models

Chin

Pang

2020

Front. Pediatr.

View full text Add to dashboard Cite

Isoflavones are dietary phytoestrogens commonly found in soy-based products. The widespread presence of isoflavones in soy infant formula and breast milk may have long-lasting effects on the development of sex hormone-sensitive organs like the skeleton. Animal early-life programming models are suitable for testing the skeletal effects of pre- and neonatal exposure of soy isoflavones. This review aims to collate the impacts of early-life exposure of soy isoflavones as evidenced in animal models. The isoflavones previously studied include daidzein, genistein, or a combination of both. They were administered to rodent pups during the first few days postnatal, but prolonged exposure had also been studied. The skeletal effects were observed when the animals reached sexual maturity or after castration to induce bone loss. In general, neonatal exposure to soy isoflavones exerted beneficial effects on the skeletal system of female rodents, but the effects on male rodents seem to depend on the time of exposure and require further examinations. It might also protect the animals against bone loss due to ovariectomy at adulthood but not upon orchidectomy. The potential benefits of isoflavones on the skeletal system should be interpreted together with its non-skeletal effects in the assessment of its safety and impacts.

show abstract

Neonatal rat age, sex and strain modify acute antioxidant response to ozone

Cited by 7 publications

References 79 publications

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Skeletal Effects of Early-Life Exposure to Soy Isoflavones—A Review of Evidence From Rodent Models

Contact Info

Product

Resources

About