The Differential Tissue Distribution of the Citrus Flavanone Naringenin Following Gastric Instillation

Abstract

Citrus flavonoids have been investigated for their biological activity, with both anti-inflammatory and -carcinogenic effects being reported. However, little information is known on the bioavailability of these compounds in vivo. The objectives of this study were to determine the tissue distribution of naringenin after gastric gavage of [3H]-naringenin to rats. Unlabelled naringenin was also used to quantify the levels of naringenin and its major metabolites in tissues and eliminated in the urine and faeces. Significant radioactivity was detected in the plasma as well as all tissues examined 2h post-gavage. After 18h, higher levels of radioactivity were retained in plasma and tissues (55% of the administered radioactivity). Investigation of the nature of metabolites, using unlabelled naringenin, revealed that the glucuronides were the major components in plasma, tissues and urine, in addition to the colonic metabolite 3-(4-hydroxyphenyl) propionic acid, detected in the urine. The aglycone was the form extensively retained in tissues after 18h post-gavage. Total identified metabolites detected after 18h in most tissues were only 1-5% of the levels detected after 2h. However, the brain, lungs and heart retained 27, 20 and 11%, respectively, relative to the total metabolites detected at 2h. While radioactive detection suggests increased levels of breakdown products of naringenin after 18 h versus 2 h, the products identified using unlabelled naringenin are not consistent with this, suggesting that a predominant proportion of the naringenin breakdown products at 18 h are retained as smaller decomposition molecules which cannot yet be identified.

Safety and pharmacokinetics of naringenin: A randomized, controlled, single‐ascending‐dose clinical trial

“…In rodent studies, dosing with naringenin or naringin produced inconsistent results. Following a single gastric gavage of naringenin (50 mg/kg) in rats, naringenin aglycone was detected at higher levels in tissues than in plasma after 18 hours . However, following gastric gavage of naringin at 210 mg/kg twice daily (17 doses) in rats, free forms of naringin and naringenin were not detected in plasma or major organs .…”

The effect of epicatechin on oxidative stress and mitochondrial damage induced by homocycteine using isolated rat hippocampus mitochondria

“…It has been demonstrated that the bioavailability of EC is greater than that of the catechin in rat(28). Also, flavonoids are able to transverse the blood-brain-barrier after oral ingestion(29). …”

A Review on Pharmacological and Analytical Aspects of Naringenin

“…(18,76) Using radiolabeled molecules, it was found that naringenin is widely distributed in brain, lungs and heart tissue, which may be inferred as its beneficial effects may extend to various organs of the body. (77) Using solid dispersion method, calcium alginatechitosan beads of naringenin having intra-gastric floating property was prepared, which showed sustained release of naringenin. (78) Effects of naringenin on the pharmacokinetics of doxorubicin in rats were investigated.…”