Ozone-induced changes in oxidative stress parameters in brain regions of adult, middle-age, and senescent Brown Norway rats

Kodavanti, Prasada Rao S.; Valdez, Matthew C.; Richards, Judy E.; Agina-Obu, DaTonye I.; Phillips, Pamela; Jarema, Kimberly; Kodavanti, Urmila P.

doi:10.1016/j.taap.2020.115351

Cited by 20 publications

(15 citation statements)

References 80 publications

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“…2018 ). Increased

exposure has resulted in oxidative stress in brains and altered nervous system function in adult rats ( Kodavanti et al. 2021 ; Martínez-Lazcano et al.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

Rahman

Shu

Chow

et al. 2022

Environ Health Perspect

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Background: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters. Objective: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort. Methods: This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ( )], nitrogen dioxide ( ), and ozone ( ) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season. Results: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) ( ) increase]. exposure during 34–37 wk of gestation was associated with increased risk [ (95% CI: 1.01, 1.11) per IQR ( ) increase] but with reduced risk during 20–28 wk of gestation [ (95% CI: 0.89, 0.98)]. No associations were observed with . Sex-stratified early gestational associations were stronger among boys [boys (95% CI: 1.08, 1.26); girls (95% CI: 0.89, 1.26)]. associations in later gestation were observed only in boys [boys (95% CI: 1.04, 1.16); girls (95% CI: 0.84, 1.05)]. Conclusions: Exposures to in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509

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“…2018 ). Increased

exposure has resulted in oxidative stress in brains and altered nervous system function in adult rats ( Kodavanti et al. 2021 ; Martínez-Lazcano et al.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

Rahman

Shu

Chow

et al. 2022

Environ Health Perspect

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“…Furthermore, intrinsic factors as age increase the susceptibility to oxidative damage. Prasada et al [ 43 ] found that exposure to 0.25 and 1 ppm for 6 h a day, 2 days a week during 13 weeks in young rats (4 months old) and senescent rats (24 months old) showed protein carbonylation in the frontal cortex at both O 3 concentrations, which were higher in the older animals.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Decreases Hippocampal Neurodegeneration and Nitro-Oxidative Damage to Plasma Proteins and Lipids Caused by Short-Term Exposure to Ozone

et al. 2021

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Neurodegeneration is the consequence of harmful events affecting the nervous system that lead to neuronal death. Toxic substances, including air pollutants, are capable of inducing neurodegeneration. Ozone (O3) is the most oxidative toxic pollutant. O3 reacts with cellular components and forms reactive oxygen and nitrogen species, triggering nitro-oxidative damage during short-term exposure. Curcumin (CUR) is a natural phenolic molecule bearing well-documented antioxidant and anti-inflammatory biological activities in diverse experimental models. The aim of this work was to evaluate the effect of preventive dietary administration of CUR against hippocampal neurodegeneration and nitro-oxidative damage caused by short-term exposure to O3. Eighty Wistar male rats were distributed into four experimental groups, twenty rats each: intact control; CUR dietary supplementation without O3 exposure; exposure to 0.7 ppm of O3; and exposed to O3 with CUR dietary supplementation. Five rats from each group were sacrificed at 1, 2, 4, and 8 h of exposure. The CUR dose was 5.6 mg/kg and adjusted according to food consumption. CUR significantly decreased oxidative damage to plasma lipids and proteins, as well as neurodegeneration in CA1 and CA3 hippocampal regions. Concluding, CUR proved effective protection in decreasing neurodegeneration in the hippocampus and prevented systemic oxidative damage.

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“…The effects of O 3 exposure on the brain have garnered interest in recent years [ 20 , 33 , 34 , 35 , 36 , 37 ]. O 3 itself is a highly reactive oxidizer, which does not translocate distally in its parent chemical form.…”

Section: Resultsmentioning

confidence: 99%

“…However, many of the effects in the brain seem to be mediated by indirect modes of action, such as by sensory reception or other signaling cascades [ 13 , 38 ]. Due to the chemical nature of O 3 , OS as an adverse outcome is most typically associated with exposure [ 33 , 39 , 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific

Valdez

Freeborn

Vulimiri

et al. 2023

IJMS

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Exposure to a prototypic air pollutant ozone (O3) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer’s disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O3 in stress responsive regions are sex-dependent. Male and female adult Long–Evans rats were exposed to filtered air or O3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O3. There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O3-exposed females relative to matched males. Microglial marker Aif1 expression was higher in O3-exposed females relative to males; O3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O3-exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O3 might, in part, be caused by OS and regulation of glucocorticoid signaling.

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Ozone-induced changes in oxidative stress parameters in brain regions of adult, middle-age, and senescent Brown Norway rats

Cited by 20 publications

References 80 publications

Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

Curcumin Decreases Hippocampal Neurodegeneration and Nitro-Oxidative Damage to Plasma Proteins and Lipids Caused by Short-Term Exposure to Ozone

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific

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