Changes in oxidative nucleic acid modifications and inflammation following one-week treatment with the bile acid sequestrant sevelamer: Two randomised, placebo-controlled trials

Abstract

Aims: Sevelamer has been reported to have anti-oxidative and anti-inflammatory effects as well as effects on glycaemic control and plasma lipids. The aim of this study was to determine the effects of one-week treatment with sevelamer on oxidative nucleic acid modifications and inflammation markers.

Methods: Two double-blinded studies including 30 patients with type 2 diabetes (T2D) and 20 healthy individuals were conducted. Participants were randomised to one week of treatment with sevelamer (1600 mg three times daily) or placebo. RNA and DNA oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine(8-oxoGuo) and (8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG), and markers of inflammation were determined before and after the intervention.

Results: In patients with T2D there was no significant placebo-corrected reduction in 8-oxoGuo or 8-oxodG. However, a reduction in 8-oxoGuo was observed within the group treated with sevelamer (∆8-oxoGuo/creatinine (median[IQR]): -0.04 [-0.24; 0.01] nmol/mmol, p = 0.02). A sevelamer-mediated reduction in interleukin-2 (p = 0.04) and a trend towards reduction in interleukin-6 (p = 0.053) were found in patients with T2D.

Conclusions: This study reveals a potential effect of sevelamer treatment on inflammation and possible oxidative RNA modifications. The potential protective effects of sevelamer in terms of cardiovascular disease in patients with T2D need further investigation.

Keywords: 8-oxo-7,8-dihydro-2′-deoxyguanosine; 8-oxo-7,8-dihydro-guanosine; Inflammation; Oxidative stress; Sevelamer; Type 2 diabetes mellitus.