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PPARα (-/-) and wild-type (WT) female mice were exposed for 14 days to vehicle or 2,4-DNT (134 mg/kg/day) and performed a forced swim to exhaustion 1 day after the last dose.2,4-DNT significantly decreased body weights and swim times in WTs, but effects were significantly mitigated in PPARα (-/-) mice.As a result of its extensive use in ordnance and propellant production, 2,4-DNT has been found to contaminate soil at artillery ranges and demilitarization areas and surrounding waste water streams at munitions manufacturing sites leading to its listing on EPA's Contaminate Candidate List (Pontius, 1997).
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The overall design enabled us to examine if 2,4-DNT interacted directly with PPARα to cause physiological impacts on performance as postulated in the AOP.
2,4-DNT (97%, CAS number 121–14–2), dimethyl sulfoxide (DMSO), and corn oil were obtained from Sigma-Aldrich (St. C57Bl/6N (WT) and PPARα (-/-) (catalog number TF3135) age-matched female mice (20 g) were purchased from Taconic Farms (Hudson, NY) and housed and treated in accordance with the daily.
Study protocols were pre-approved by the Institutional Animal Care and Use Committees of the University of Louisiana at Monroe and US Army Engineer Research and Development Center.
A range-finding study was conducted to determine a 2,4-DNT dose without overt systemic toxicity to mice.
Nitroaromatic compounds are commonly used in manufacture of both industrial compounds and explosives used by the military and commercially.
2,4-dinitrotoluene (2,4-DNT) is used as an intermediate in production of polyurethane polymers, dyes, and explosives (ATSDR, 1998).
Groups of mice were weighed and randomly assigned to four treatment groups, each containing four mice, including vehicle (5% DMSO in corn oil, vol/vol) or 2,4-DNT (134, 402, 670 mg/kg/day in vehicle).
The high dose of 670 mg/kg/day was selected based on 50% of the acute LD dose for female Swiss and CF-1 mice for 2,4-DNT (ATSDR, 1998).
2,4-DNT decreased transcript expression for genes downstream in the PPARα signaling pathway, principally genes involved in fatty acid transport.
Results indicate that PPARγ signaling increased resulting in enhanced cycling of lipid and carbohydrate substrates into glycolytic/gluconeogenic pathways favoring energy production versus storage in 2,4-DNT-exposed WT and PPARα (-/-) mice.
However, the direct linkage between these molecular-level impacts and weight loss and other adverse effects at the individual level has not been tested.Tags: Adult Dating, affair dating, sex dating