Combined exposure to DEET (N,N-diethyl-m-toluamide) and permethrin-induced release of rat brain mitochondrial cytochrome c.
The release of cytochrome c from the mitochondrial intermembrane space can induce apoptosis. The levels of mitochondrial cytochrome c in rat brain following a single dermal dose of 400 mg/kg of DEET, and of 1.3 mg/kg of permethrin, alone or in combination were determined. Rats were sacrificed at a time interval of 0.5, 1, 2, 4, 8, 16, 24, 48, or 72 h after dosing. Brain mitochondria were isolated and the levels of cytochrome c were measured using reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Average percentage recovery of cytochrome c spiked with control rat brain mitochondria was 83.2 +/- 8.9%. Limits of detection and quantitation were 1 and 5 ng, respectively. The results showed that a single dermal dose of a combination of DEET and permethrin significantly increased the release of brain mitochondrial cytochrome c starting 24 h after treatment. DEET and permethrin alone did not affect the release of cytochrome c. The results indicate that combined exposure to DEET and permethrin might induce the apoptotic processes in rat brain as seen by the release of cytochrome c.
Abu-Qare
A W
AW
Department of Pharmacology and Cancer Biology, Duke University  Medical Center, Durham, North Carolina 27710, USA.
Abou-Donia
M B
MB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003574:Cytochrome c Group / Q000378:metabolism*; D003671:DEET / Q000494:pharmacology*; D007302:Insect Repellents / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D026023:Permethrin; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D003574:Cytochrome c Group; D007302:Insect Repellents; D007306:Insecticides; D011722:Pyrethrins; D003671:DEET; D026023:Permethrin