4-Methylumbeliferone Treatment at a Dose of 1.2 g/kg/Day Is Safe for Long-Term Usage in Rats

Author:

Štěpánková Kateřina12ORCID,Mareková Dana12,Kubášová Kristýna3ORCID,Sedláček Radek3ORCID,Turnovcová Karolína1,Vacková Irena14,Kubinová Šárka15,Makovický Pavol6,Petrovičová Michaela1,Kwok Jessica C. F.17ORCID,Jendelová Pavla12ORCID,Machová Urdzíková Lucia12ORCID

Affiliation:

1. Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague, Czech Republic

2. Department of Neuroscience, Second Faculty of Medicine, Charles University, 15006 Prague, Czech Republic

3. Department of Mechanics, Biomechanics and Mechatronics, Faculty of Mechanical Engineering, Czech Technical University in Prague, 16000 Prague, Czech Republic

4. Institute of Physiology, Czech Academy of Sciences, 14220 Prague, Czech Republic

5. Institute of Physics, Czech Academy of Sciences, 18221 Prague, Czech Republic

6. Department of Biology, Faculty of Education, J. Seyle University, SK-94501 Komarno, Slovakia

7. School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK

Abstract

4-methylumbelliferone (4MU) has been suggested as a potential therapeutic agent for a wide range of neurological diseases. The current study aimed to evaluate the physiological changes and potential side effects after 10 weeks of 4MU treatment at a dose of 1.2 g/kg/day in healthy rats, and after 2 months of a wash-out period. Our findings revealed downregulation of hyaluronan (HA) and chondroitin sulphate proteoglycans throughout the body, significantly increased bile acids in blood samples in weeks 4 and 7 of the 4MU treatment, as well as increased blood sugars and proteins a few weeks after 4MU administration, and significantly increased interleukins IL10, IL12p70 and IFN gamma after 10 weeks of 4MU treatment. These effects, however, were reversed and no significant difference was observed between control treated and 4MU-treated animals after a 9-week wash-out period.

Funder

Center of Reconstruction Neuroscience—NEURORECON

Czech Science Agency

Wings for Life

Medical Research Council UK

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference68 articles.

1. Cation-anion gap and choleretic properties of rat bile;Klos;Am. J. Physiol. -Endocrinol. Metab.,1979

2. The role of mdr2 P-glycoprotein in hepatobiliary lipid transport;Elferink;FASEB J.,1997

3. The choleretic mechanism of coumarin compounds and phenolic compounds;Takeda;J. Pharm.,1981

4. 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition;Nagy;J. Biol. Chem.,2019

5. Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice;Dubisova;Brain Res. Bull.,2022

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