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

Shannon Doherty Lyons, Jason L. Blum, Carol Hoffman-Budde, Pamela B. Tijerina, M. Isabel Fiel, Daniel J. Conklin, Francesca Gany, Joseph A. Odin and Judith T. Zelikoff
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Shannon Doherty Lyons: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA
Jason L. Blum: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA
Carol Hoffman-Budde: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA
Pamela B. Tijerina: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA
M. Isabel Fiel: Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Daniel J. Conklin: American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Kentucky, KY 40202, USA
Francesca Gany: Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
Joseph A. Odin: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Judith T. Zelikoff: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA

IJERPH, 2020, vol. 17, issue 21, 1-15

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.

Keywords: smokeless tobacco; developmental origins of health and disease; gutkha; hepatic; liver disease (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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