Hydrolytic metabolism of phenyl and benzyl salicylates, fragrances and flavoring agents in foods, by microsomes of rat and human tissues. (December 2015)

• Record Type: Journal Article
• Authors: Ozaki, Hitomi; Sugihara, Kazumi; Tamura, Yuki; Fujino, Chieri; Watanabe, Yoko; Uramaru, Naoto; Sone, Tomomichi; Ohta, Shigeru; Kitamura, Shigeyuki
• Is Part Of: Food and chemical toxicology. Volume 86(2015)
• Page Start: 116
• Page End: 123
• Publication Date: 2015-12
• Subjects: Carboxylesterase -- Human liver and small-intestinal microsomes -- Hydrolytic metabolism -- Rat tissue microsomes -- Salicylate -- Salicylic acid; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2015.08.024
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Salicylates are used as fragrance and flavor ingredients for foods, as UV absorbers and as medicines. Here, we examined the hydrolytic metabolism of phenyl and benzyl salicylates by various tissue microsomes and plasma of rats, and by human liver and small-intestinal microsomes. Both salicylates were readily hydrolyzed by tissue microsomes, predominantly in small intestine, followed by liver, although phenyl salicylate was much more rapidly hydrolyzed than benzyl salicylate. The liver and small-intestinal microsomal hydrolase activities were completely inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. Phenyl salicylate-hydrolyzing activity was co-eluted with carboxylesterase activity by anion exchange column chromatography of the Triton X-100 extracts of liver and small-intestinal microsomes. Expression of rat liver and small-intestinal isoforms of carboxylesterase, Ces1e and Ces2c (AB010632 ), in COS cells resulted in significant phenyl salicylate-hydrolyzing activities with the same specific activities as those of liver and small-intestinal microsomes, respectively. Human small-intestinal microsomes also exhibited higher hydrolyzing activity than liver microsomes towards these salicylates. Human CES1 and CES2 isozymes expressed in COS cells both readily hydrolyzed phenyl salicylate, but the activity of CES2 was higher than that of CES1. These results indicate that significant amounts of salicylic acid might be formed by microsomal hydrolysis of phenyl and benzyl salicylates in vivo . The possible pharmacological and toxicological effects of salicylic acid released from salicylates present in commercial products should be considered. Highlights: Phenyl and benzyl salicylates are used as fragrances and flavoring agents in foods. These salicylates are rapidly hydrolyzed by tissue microsomes of rats and humans. Ces1e and Ces2c (AB010632 ) are major contributors to hydrolysis of phenyl salicylate. Benzyl salicylate is mainly hydrolyzed by rat Ces1e and Ces2a. Human CES1 and CES2 are major contributors to hydrolysis of these salicylates.