Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

Autor: Jennifer Ngolab, Xinyang Bing, Rubing Zhao-Shea, Paul D. Gardner, Markus Vallaster, Oliver J. Rando, Shweta Kukreja, Andrew R. Tapper
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Mouse
Drug Resistance
Nicotine
chemistry.chemical_compound
Mice
0302 clinical medicine
Paternal Effects
substance abuse
Nicotinic Agonists
Biology (General)
Genetics
General Neuroscience
General Medicine
Receptor antagonist
Nicotinic agonist
Liver
Genes and Chromosomes
Inactivation
Metabolic
Paternal Exposure
Paternal Inheritance
Medicine
Female
Insight
medicine.drug
medicine.medical_specialty
QH301-705.5
medicine.drug_class
Offspring
Science
Biology
General Biochemistry
Genetics and Molecular Biology
Xenobiotics
03 medical and health sciences
Downregulation and upregulation
Internal medicine
medicine
Animals
General Immunology and Microbiology
epigenetics
Environmental Exposure
Survival Analysis
030104 developmental biology
Endocrinology
chemistry
Xenobiotic
030217 neurology & neurosurgery
Drug metabolism
Zdroj: eLife
eLife, Vol 6 (2017)
ISSN: 2050-084X
Popis: Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal ‘quality of life’. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics.
Databáze: OpenAIRE
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