Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients.

Abstract

It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis. Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.