Pharmacokinetics and tissue distribution of orally administrated imidazole dipeptides in carnosine synthase gene knockout mice

Abstract

Imidazole dipeptides (ID) are abundant in skeletal muscle and the brain and have various functions, such as antioxidant, pH-buffering, metal-ion chelation. However, the physiological significance of ID has not been fully elucidated. In this study, we orally administered ID to conventional carnosine synthase gene-deficient mice (Carns-KO mice) to investigate the pharmacokinetics. Carnosine or anserine was administered at a dose of 500 mg (approximately 2 mmol) per kilogram of mouse body weight, and ID contents in the tissues were measured. No ID were detected in untreated Carns-KO mice. In the ID treatment groups, the ID concentrations in the tissues increased in a time-dependent manner in the gastrocnemius muscle, soleus muscle, and cerebrum after ID administration. Our findings suggest that the Carns-KO mice are a valuable animal model for directly evaluate the effects of dietary ID and for elucidating the physiological functions of oral ID administration.

Anti-Hyperuricemic Effect of Anserine Based on the Gut–Kidney Axis: Integrated Analysis of Metagenomics and Metabolomics

“…It is reported that, in general, bonito, bigeye tuna, and southern tuna contain about 1070 mg, 1260 mg and 636 mg of anserine per 100 g of fish flesh, respectively [ 17 ]. We learned that the doses of anserine used in previous animal experiments ranged from 2 mg/kg·bw to 80 mg/kg·bw [ 18 , 19 ], so we chose the 1 mg/10 mg/100 mg kg·bw as the low/medium/high doses of anserine intervention in our experiment. Our results did show that medium doses of anserine were the most effective in improving hyperuricemia.…”

Anserine and Carnosine Induce HSP70-Dependent H2S Formation in Endothelial Cells and Murine Kidney

“…Carnosine is provided by nutrition and tissue carnosine synthase (Carns1), but the impact of the latter is uncertain. In Carns1-KO mice, brain and muscle are carnosine-deficient, and stores can be replenished by oral intake [44], but the Carns1-KO had no impact on kidney and brain markers of carbonyl and oxidative stress in healthy and diabetic mice [45]. In contrast, anserine and carnosine are rapidly degraded by CN1, and kidney tissue CN1 activity in healthy and in type 2 diabetic mice is correlated with kidney anserine and carnosine concentrations and the tissue carbonyl and oxidative stress level [46].…”

Embryonic Cadaverine Signaling: Implications for Plasma Free Amino Acid and Skeletal Muscle Energy Metabolism in Newly Hatched Chicks

“…Following the method described by Sakano et al [ 17 ], plasma free amino acid (arginine, lysine, methionine, isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, histidine, glycine, glutamic acid, glutamine, aspartic acid, serine, alanine, cysteine, tyrosine, proline, taurine, N π -methylhistidine, and N τ -methylhistidine) concentrations were determined using a fully automated amino acid analyzer (JLC-500/V2, Japan Electron Optics Laboratory, Tokyo, Japan) after plasma samples were deproteinized with 3% sulfosalicylic acid solution.…”