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DIFFERENTIAL EFFECTS OF POLYBROMINATED DIPHENYL ETHERS AND POLYCHLORINATED BIPHENYLS ON [3H]ARACHIDONIC ACID RELEASE IN RAT CEREBELLAR GRANULE NEURONS.
Citation:
KODAVANTI, PRASADA RAO S. AND E. DERR-YELLIN. DIFFERENTIAL EFFECTS OF POLYBROMINATED DIPHENYL ETHERS AND POLYCHLORINATED BIPHENYLS ON [3H]ARACHIDONIC ACID RELEASE IN RAT CEREBELLAR GRANULE NEURONS. TOXICOLOGICAL SCIENCES 68:451-457, (2002).
Description:
Polybrominated diphenyl ethers (PBDEs), which are widely used as flame-retardants, have been increasing in the past 20-30 years while the presence of other structurally related persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (on a TEQ basis), have decreased in environmental and human tissue samples. PBDEs have been detected in human blood, adipose tissue, and breast milk; and, developmental and long-term exposure to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that PCBs, which cause neurotoxic effects including changes in learning and memory, stimulated the release of [3H]arachidonic acid ([3H]AA) by a cPLA2/iPLA2 dependent mechanism. PLA2 (phospholipase A2) activity has been associated with learning and memory, and AA has been identified as a second messenger involved in synaptic plasticity. The objective of the present study is to test whether PBDE mixtures (DE-71 and DE-79), like other organohalogen mixtures, have a similar action on [3H]AA release in an in vitro neuronal culture model. Cerebellar granule cells at seven days in culture were labeled with [3H]AA for 16-20 hours and then exposed in vitro to PBDEs. DE-71, a mostly pentabromodiphenyl ether mixture, significantly stimulated [3H]AA release at concentrations as low as 10 g/ml while DE-79, a mostly octabromodiphenyl ether mixture, did not stimulate [3H]AA release even at 50 g/ml. The release of [3H]AA by DE-71 is time-dependent and a significant increase was seen as early as 5-10 min of exposure. The removal and chelation of calcium from the exposure buffer using 0.3 mM EGTA, significantly attenuated the DE-71-stimulated [3H]AA release; however, only an 18% inhibition of the release was demonstrated for the calcium replete conditions at 30 g/ml DE-71. Methyl arachidonylfluorophosphonate (5 M), an inhibitor of cPLA2/iPLA2, completely attenuated the DE-71-stimulated [3H]AA release. Further studies focused on comparing the effects of DE-71 with PCB mixtures such as Aroclor 1016 and Aroclor 1254. Both PCB mixtures stimulated [3H]AA release in a concentration-dependent manner, however, the effect for PCBs was about two-times greater than that of the PBDEs on a weight basis but was comparable on a molar basis. These results indicate that PBDEs stimulated the release of [3H]AA by activating PLA2, which is similar to the effect of other organohalogen mixtures.
Key words: Polybrominated diphenyl ethers, Brominated flame retardants, Arachidonic acid release, Polychlorinated biphenyls, Phospholipases, Neurotoxicity.