# The Effect of Serum Carnosinase on the Tissue Distribution of Imidazole Dipeptides After Their Oral Administration in Golden Hamsters

## TL;DR

This study examines how serum carnosinase in golden hamsters affects the distribution of imidazole dipeptides after oral administration, highlighting differences between primates and non-primates.

## Contribution

The study identifies the role of carnosinase in hamsters and its impact on imidazole dipeptide metabolism, suggesting hamsters as a relevant model for human studies.

## Key findings

- Hamster plasma CN1 activity is over 10 times higher than in humans.
- Oral IDP administration increases m-His levels in hamster tissues.
- IDP-treated hamster tissues show higher IDP levels compared to controls.

## Abstract

Background/Objectives: Imidazole dipeptides (IDPs), carnosine and anserine, are endogenous antioxidants. The metabolism and functions of IDPs have mainly been investigated in rodents. However, the blood of primates, such as humans, contains carnosinase (CN1), which hydrolyzes IDPs. In non-primates, CN1 is absent, allowing IDPs to be distributed throughout tissues. There are concerns about whether the results of animal experiments can be directly applied to humans. Therefore, we aimed to investigate the blood change in the concentration and tissue distribution of IDPs following their oral administration to golden hamsters, the only non-primates known to possess CN1. Methods: Plasma CN1 activity was compared between hamsters and humans. Hamsters were administered IDPs (an anserine/carnosine mixture) purified from chicken meat at a dose of 1000 mg/kg. Blood samples were collected at time points up to 6 h after administration. Tissue samples were collected at 6 h after administration to measure the concentrations of IDPs and related substances. Additionally, IDP levels in human and mice tissues from previous studies were compared with that of hamster tissues in this study. Results: Hamster plasma CN1 activity was more than 10 times higher than that in humans. Although IDPs were not detected in IDP-treated hamster plasma, constituent amino acids of IDPs increased up to 1–2 h and Nπ-methyl-histidine (m-His) remained at high levels up to 6 h after administration. IDP levels in control tissues (vehicle) were similar to those in human tissues. In the IDP group, tissue IDPs were higher than those in the vehicle and m-His increased in all tissues. Conclusions: This study indicated that m-His levels increase in hamster tissues following a single oral administration of IDPs and strongly suggest that hamsters should be used in functional studies of IDPs in humans, focusing on the functionality of m-His.