Safety evaluation of naringenin upon experimental exposure on rat gastrointestinal epithelium for novel optimal drug delivery.

Objective: To assess the effect of naringenin on the intestinal biochemical composition, function and histology for gastrointestinal toxicity since it has not yet been adequately exploited for safety through standard assays.

Methods: Here, we describe naringenin (1 mM, 10 mM and 100 mM, respectively) or sodium deoxycholate (10 mM) effects on isolated brush border membrane from intestinal segments with single pass intestinal perfusion using lactate dehydrogenase, alkaline phosphatase and protein assays. MTT assay was used for cytotoxicity studies. Everted gut sac studies were used for evaluating the transport of nutrients across the intestinal segments. Lucifer yellow was used for paracellular permeability, followed by histological changes and surface characteristic studies of intestinal sacs.

Results: The results indicated no significant alterations with naringenin, although significant (p < 0.01) changes were noticed with sodium deoxycholate in the activity of the rat intestinal brush border associated enzymes such as LDH, followed by intact cell viability with marked decrease in the villi height of the intestinal segments.

Conclusions: These observations indicate that naringenin was harmless upon exposure to rat gastrointestinal epithelium, clearly demonstrating the potential use of naturally occurring bioflavonoid as safe and novel pharmaceutical adjuvant in oral dosage forms as P-gp inhibitor.