High phthalate exposure increased urinary concentrations of quinolinic acid, implicated in the pathogenesis of neurological disorders: Is this a potential missing link?
| Autor: | Melissa M Hill, Joshua A. Gunn, Brent A. Coull, Russ Hauser, Feiby L. Nassan |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Kynurenine pathway Dibutyl phthalate Metabolite Phthalic Acids Pilot Projects Urine 010501 environmental sciences Pharmacology 01 natural sciences Biochemistry Article Excretion 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans Medicine Prospective Studies 030212 general & internal medicine 0105 earth and related environmental sciences General Environmental Science Creatinine business.industry Phthalate Quinolinic Acid Crossover study Rats Cross-Sectional Studies chemistry Nervous System Diseases business circulatory and respiratory physiology |
| Zdroj: | Environ Res |
| ISSN: | 0013-9351 |
| DOI: | 10.1016/j.envres.2019.02.034 |
| Popis: | Background Quinolinic acid (QA), a neuroactive metabolite of the Kynurenine Pathway (KP), is an excitotoxin that is implicated in the pathogenesis of many neurological disorders. KP is the main tryptophan degradation pathway. Phthalates can structurally mimic tryptophan metabolites and diets containing phthalates in rats enhanced the production and excretion of QA. However, there are no human studies that have examined the association between phthalates and QA. Objectives Taking advantage of different mesalamine formulations with/without dibutyl phthalate (DBP), we assessed whether DBP from mesalamine (>1000x background) altered the urinary concentrations of QA. Methods Men with inflammatory bowel disease participated in a prospective crossover pilot study. 15 Men were on non-DBP mesalamine (background) at baseline crossed-over for 4 months to high-DBP mesalamine (high) (B1H-Arm) and vice versa for 15 men who were on high-DBP mesalamine at baseline (H1B-Arm). Men provided 60 urine samples (2/man). We estimated crossover and cross-sectional changes in the creatinine normalized-QA using multivariable linear mixed effect models with random intercepts. Results At baseline, men who were on high-DBP mesalamine (H1B-Arm) had 72%, (95% confidence interval (CI): 18, 151) higher normalized-QA than men who were on background exposure and when high-DBP mesalamine was removed for four months, normalized-QA decreased with 32%, (95% CI: −45.0, −15.1). Consistently, when men in B1H-Arm were newly-exposed to high-DBP mesalamine, normalized-QA increased with 11%, (95% CI: −11, 38). Conclusions High-DBP exposure from mesalamine increased the urinary concentrations of QA, which was largely reversed after removal of the high-DBP exposure for four months. This novel hypothesis should warrant new promising research considering the KP and QA concentrations as a plausible mediator for the neurotoxicity possibly linked with phthalate exposures. |
| Databáze: | OpenAIRE |
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