Sodium 4‑phenylbutyrate inhibits protein glycation

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.