Sodium 4‑phenylbutyrate inhibits protein glycation

Ono,Kazuhiko; Nakashima,Manabu

doi:10.3892/br.2020.1368

Sodium 4‑phenylbutyrate inhibits protein glycation

Authors:
- Kazuhiko Ono
- Manabu Nakashima
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Affiliations: Department of Drug Informatics and Translational Research, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814‑0180, Japan, Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814‑0180, Japan
Published online on: October 15, 2020 https://doi.org/10.3892/br.2020.1368
Article Number: 61

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Abstract

The production and accumulation of advanced glycation end‑products (AGEs) are hypothesized to have a causal role in the development of the complications associated with aging and lifestyle‑related diseases, such as diabetes, atherosclerosis and hyperlipidemia. Therefore, it is important to reduce the production and accumulation of AGEs. In the present study, the ability of sodium 4‑phenylbutyrate (PBA) on inhibition of glycation was assessed. In vitro, PBA inhibited the glycation of albumin and collagen by up to 42.1 and 36.9%, respectively. Furthermore, when spontaneously diabetic KK mice were administered PBA (20 mg/day) or vehicle orally, glycosuria developed rapidly in the control mice, but after 6 weeks, only one treated mouse was glycosuric. In addition, the weight gain and HbA1c levels were significantly lower in the treated mice compared with the untreated mice (weight gain, 36.0 g vs. 39.4 g, P<0.01; HbA1C level, 3.96 vs. 4.78%, P<0.01; respectively). These results suggested that PBA also inhibited glycation in vivo. Further studies are required to determine whether PBA may be effective for the therapy or prevention of aging or lifestyle‑related diseases caused by the accumulation of AGEs. The method of administration and the side‑effects of PBA have already been established as PBA is already used clinically. Therefore, the repurposing of PBA for reducing AGE levels may be a potential option to reduce complications associated with aging.

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