Plasma and Urine Concentrations of Bioactive Dietary Benzoxazinoids and Their Glucuronidated Conjugates in Rats Fed a Rye Bread-Based Diet

Abstract

Thorough knowledge of the absorption and metabolism of dietary benzoxazinoids is needed to understand their health-promoting effects. In this study, the fates of these bioactive compounds were examined by LC-MS/MS in plasma, urine, and feces after ingesting a daily dose of 4780 ± 68 nmol benzoxazinoids from rye bread using Wistar rats as a model. HBOA-glc (2-β-D-glucopyranosyloxy-1,4-benzoxazin-3-one) was the predominant benzoxazinoid in the plasma (74 ± 27 nmol/L), followed by DIBOA-glc (2-β-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one) and HBOA. The total level of benzoxazinoids in the urine was 1176 ± 66 nmol/d, which corresponds to approximately 25% of the total dietary intake. The urinary benzoxazinoid profile differed from that of plasma with HBOA-glc and DIBOA-glc (647 ± 31 and 466 ± 33 nmol/d, respectively) as the major urinary components. The glucuronide conjugates of HBOA and DIBOA were detected in both the plasma and urine. N-dehydroxylation was found to be a critical step in the absorption of hydroxamic acids. This unprecedented study will trigger future interest in the biological effects of benzoxazinoids in whole grain rye and wheat diets in humans and other animals.

The Postprandial Plasma Rye Fingerprint Includes Benzoxazinoid-Derived Phenylacetamide Sulfates

“…Recently, there were several targeted, quantitative approaches on the characterization of bioavailability and absorption of dietary benzoxazinoids in rats (17), pigs (16), and humans (18). In rats, 3 benzoxazinoid compounds (HBOA, HBOA glucose, and DIBOA glucose) were detected in plasma 3 h after feeding (17).…”

“…In rats, 3 benzoxazinoid compounds (HBOA, HBOA glucose, and DIBOA glucose) were detected in plasma 3 h after feeding (17). In humans, circulating plasma benzoxazinoids were detected 1-3 hours after the intake of a benzoxazinoid-rich breakfast and were identified as HBOA glucose and DIBOA glucose with negligible amount of HBOA (18).…”

“…Several compounds of the benzoxazinoid class were detected in the plasma and urine of pigs (16) and rats (17) and in a human study showing the postprandial appearance of benzoxazinoids in circulation and urine (18). In addition to these studies using targeted, quantitative assays, a recent nontargeted metabolite profiling study indicated phenylacetamides as the predominant urine metabolites of benzoxazinoids (19).…”

Plant defense and herbivore counter-defense: benzoxazinoids and insect herbivores

“…Ingestion of rye bread which naturally contains a mixture of BXDs has revealed some aspects of BXD metabolism in mammals. For example, in rats and pigs, glucoside hydrolysis, hydroxamic acid reduction to the corresponding lactam, and aglucone conjugation to glucuronic acid were important metabolic reactions (Adhikari et al 2012a, b). In humans, hydroxamic acid reduction and aglucone conjugation with glucuronic acid and sulfate were observed (Adhikari et al 2013).…”

Glycosylated Benzoxazinoids Are Degraded during Fermentation of Wheat Bran

“…9 Another study in rats fed a ryebased diet showed that certain benzoxazinoids were detected in plasma and urine as glucuronidated conjugates. 10 In a recent human study consumption of whole grain sourdough rye bread was found to increase urinary content of a HBOA glucuronide. 11 Interestingly, also a novel metabolite group, namely, hydroxylated phenylacetamides, was described to be excreted in urine as sulfate or glucuronide conjugate after rye consumption.…”