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DIBROMOACETIC ACID ATTENUATES A DIMETHYLDITHIOCARBAMATE-INDUCED SUPPRESSION OF THE RAT LH SURGE
Citation:
Goldman, J M., A S. Murr, A R. Buckalew, W. K. McElroy, AND J M. Ferrell. DIBROMOACETIC ACID ATTENUATES A DIMETHYLDITHIOCARBAMATE-INDUCED SUPPRESSION OF THE RAT LH SURGE. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
DIBROMOACETIC ACID ATTENUATES A DITHIOCARBAMATE-INDUCED SUPPRESSION OF THE LH SURGE IN THE RAT. Jerome M. Goldman, Ashley S. Murr, Angela R. Buckelew, W. Keith McElroy and Janet M. Ferrell. Repro. Toxicol. Div., NHEERL, ORD, US EPA, RTP, NC
At elevated concentrations, the haloacetic acid, dibromoacetic acid (DBA) can act as a reproductive toxicant in both male and female rats. One effect in females is an increase in levels of serum estradiol (E2) that may be due to a suppression in hepatic catabolism. In the rat, the normal rise in E2 beginning on diestrus up-regulates the brain mechanisms involved in triggering the proestrous luteinizing hormone surge (LH-S) that stimulates the process of ovulation. The present study investigated a potential augmentation by DBA on the LH-S and any effect of exposure on the established ability of the neurotoxicant sodium dimethyldithiocarbamate (DMDC) to block the surge in ovariectomized (ovxed), steroid-primed rats. Two experiments were performed: (1) to establish a dose-related DMDC suppression in the LH surge under a 2 wk exposure to a single concentration of DBA and (2) to determine a dose-related effect of on the LH-S of DBA combined with a single dose of DMDC. Young-adult S-D rats were gavaged daily for 2 wks with DBA. They were ovxed on d11 and implanted with an estradiol benzoate capsule to generate daily LH-Ss. DMDC was injected i.p. on day 14 (1300h) & blood sampled at 1400, 1600, 1800 & 2000h. DMDC (0-0.2 mM/kg) caused a dose-related suppression in the surge. As a result, 0.1 mM DMDC was employed in Exp. 2, using DBA doses of 0, 37.5, 75 & 150 mg/kg. Since the areas under the LH curve (AUC) for the 2 lower doses (0 & 37.5) were almost identical, as were the AUC for the 2 higher doses (75 and 150), they were combined, forming high & low DBA groups, which were significantly different from one another. Also, the number of animals showing a detectable LH-S was increased at 150 mg/kg. At 150 mg/kg, the time of an identifiable LH peak was comparable to non-DMDC females, unlike the 37.5 mg/kg group. The results indicate that DBA can at least partly ameliorate a dithiocarbamate blockade of the LH-S via a likely augmentation in the E2-associated up-regulation in the brain mechanisms stimulating the surge. (This abstract does not reflect US EPA policy)