Dataset Information

Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.

ABSTRACT: Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring: risk factors for the progression of NAFLD to cirrhosis in adults remain elusive. Buccal cavity 'painting' of pregnant mice with gutkha began on gestational days (GD) 2-4 and continued until parturition. Beginning at 12 weeks of age, a subset of offspring were transitioned to a high-fat diet (HFD). Results demonstrated that prenatal exposure to gutkha followed by an HFD in adulthood significantly increased the histologic evidence of fatty liver disease only in adult male offspring. Changes in hepatic fibrosis-related cytokines (interleukin (IL)-1b and IL-6) and in hepatic collagen mRNA expression were observed when comparing adult male offspring exposed to gutkha in utero to those not exposed. These findings indicate that maternal use of gutkha during pregnancy affects NAFLD in adult offspring in a sex-dependent manner.

SUBMITTER: Doherty Lyons S

PROVIDER: S-EPMC7662769 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.

Doherty Lyons Shannon S Blum Jason L JL Hoffman-Budde Carol C Tijerina Pamela B PB Fiel M Isabel MI J Conklin Daniel D Gany Francesca F Odin Joseph A JA Zelikoff Judith T JT

International journal of environmental research and public health 20201028 21

Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring ...[more]

PMID: 33126512

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Project description:IntroductionApproximately the same percentage of male high school students in the United States currently uses conventional smokeless tobacco as smokes cigarettes, resulting in toxin exposure.MethodsThis study assessed tobacco product use (smokeless, combustible, and electronic cigarettes) and nicotine and carcinogen exposures in a sample of 594 male rural high school baseball players-a population traditionally at risk for smokeless tobacco use. Salivary specimens were assayed for cotinine (a biomarker of nicotine exposure) and urine specimens for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a biomarker of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) using liquid chromatography-tandem mass spectrometry.ResultsThe prevalence of past 30-day use of any tobacco product was 29%. Past 7-day smokeless tobacco use (prevalence: 13%) was associated with the highest levels of cotinine and NNAL observed in the sample, whether smokeless tobacco was used exclusively (geometric means: cotinine 11.1 ng/mL; NNAL 31.9 pg/mg-creatinine) or in combination with combustible products (geometric means: cotinine 31.6 ng/mL; NNAL 50.0 pg/mg creatinine). Cotinine and NNAL levels were incrementally higher in each increasing category of smokeless tobacco use frequency. However, observed levels were lower than previously reported for adults, likely reflecting less smokeless use per day among adolescents.ConclusionsBased on these biomarker observations, adolescents who use conventional smokeless tobacco products are exposed to substantial levels of nicotine and NNK. Although exposed to lower levels than adult smokeless users, the findings are concerning given the young age of the sample and tendency for smokeless tobacco users to increase use intensity over time.ImplicationsThis study demonstrates that adolescents using smokeless tobacco are exposed to levels of nicotine and NNK that increase with use frequency and that exceed exposures among peers using other tobacco products. Youth smokeless tobacco use in the United States has not declined along with youth smoking prevalence, giving greater importance to this health concern. To reduce youth (and adult) exposures, needed actions include effective smokeless tobacco use prevention, potentially in combination with reducing the levels of harmful and potentially harmful chemicals in smokeless tobacco products currently popular among adolescents.

Project description:Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus. Pregnant CD-1 female mice were orally administered 200 μg, 500 mg, or 750 mg/kg/day DEHP or vehicle from gestational day 11 until birth. The neurobehavioral impact of the prenatal DEHP exposure was assessed at the ages of 16-22 months. Elevated plus maze and open field tests were used to measure anxiety levels. Y-maze and novel object recognition tests were employed to measure memory function. The oxidative damage in the hippocampus was measured by the levels of oxidative DNA damage and by Spatial light interference microscopic counting of hippocampal neurons. Adult male mice that were prenatally exposed to DEHP exhibited anxious behaviors and impaired spatial and short-term recognition memory. The number of hippocampal pyramidal neurons was significantly decreased in the DEHP mice. Furthermore, DEHP mice expressed remarkably high levels of cyclooxygenase-2, 8-hydroxyguanine, and thymidine glycol in their hippocampal neurons. DEHP mice also had lower circulating testosterone concentrations and displayed a weaker immunoreactivity than the control mice to androgen receptor expression in the brain. This study found that prenatal exposure to DEHP caused elevated anxiety behavior and impaired recognition memory. These behavioral changes may originate from neurodegeneration caused by oxidative damage and inflammation in the hippocampus. Decreased circulating testosterone concentrations and decreased expression of androgen receptor in the brain also may be factors contributing to the impaired neurobehavior in the DEHP mice.

Dataset Information

Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.

Publications

Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.

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