Honors Theses and Capstones

Date of Award

Spring 2014

Project Type

Senior Honors Thesis

College or School

COLSA

Department

Biomedical Science

Degree Name

Bachelor of Science

First Advisor

Gale Carey

Abstract

Vitamin D deficiency in the Unites States has become more prevalent in recent years. Research has shown that environmental chemicals such as flame-retardants induce hepatic enzymes in the cytochrome P450 family such as CYP24 and CYP3A that are important in vitamin D metabolism. To determine if exposure to one class of flame-retardants known as polybrominated diethyl ethers (PBDEs) promotes vitamin D deficiency, 15 rats consumed a diet marginally deficient in Vitamin D - 85 IU Vitamin D/kg diet - for 56 days. On day 28 of the experiment, 7 rats were gavaged daily with 7 mg/kg BW PBDEs and 8 rats were gavaged daily with corn oil, for 28 days. Body weight and food intake were measured three times a week, vitamin D status markers in the urine were measured at weeks 4 and 8 and blood Vitamin D metabolites along with liver weight were measured at euthanization. Liver microsomal vitamin D metabolism, composition and CYP3A enzyme activity were also measured. The final body weight tended to be lower in the treatment animals than in the control but was not significantly different (370.29±40.12 vs. 400.63±31.99, respectively, p = 0.0636). Liver from PBDE-treated rats was significantly heavier than liver from control rats (15.67±1.99 vs. 12.71±0.98, respectively) p < 0.05. Liver as a percent of body weight was also significantly greater in treatment (4.24±0.2) compared to control (3.18±0.13). There was no significant difference in the lipid composition of the liver or urine metabolites between PBDE-treated and control rats. The inactive metabolites 24, 25-dihydroxy vitamin D3 and 4β, 25-dihydroxy vitamin D3 did not show significant difference between control and treatment groups. The active form of 1, 25-vitamin D3 tended to be lower in the PBDE-treated rats than in the control (0.071±0.027 vs. 0.082±0.018, respectively, p = 0.187). When expressed as a ratio to 25(OH)D3, 4β, 25-dihydroxyD3 was significantly lower in treatment rats compared to control (0.96±0.18 vs. 1.28±0.38, respectively) and 1, 25-dihydroxyD3 tended to be lower in treatment compared to control (3.62±0.96 vs. 4.44±0.97, p = 0.068). Enzymatic CYP3A levels were significantly higher in PDBE-treated rats than in control (6.047±1.53 vs. 0.103±0.032 nmol/min/mg protein, respectively). The hypothesis that the induction of CYP3A by PBDEs may accelerate vitamin D inactivation, leading to vitamin D deficiency was not supported by the findings, as there was no significant change in serum vitamin D levels in the PBDE-treated rats.

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