Elevated circulating levels of markers of oxidative-nitrative stress and inflammation in a genetic rat model of metabolic syndrome

Abstract

Metabolic syndrome is a cluster of metabolic diseases that in essence greatly promotes progression of atherosclerosis. We used a genetic model of the metabolic syndrome, the SHR/NDmcr-cp (SHR/cp) rat, from 6 to 40 weeks of age to investigate whether systemic oxidative stress, a major cause of atherosclerosis, increases in this syndrome. Nine-week-old male rats already showed manifestations of metabolic syndrome, including heavier body weight, higher blood pressure and higher levels of serum glucose, insulin and various lipids compared to the age-matched Wistar Kyoto (WKY) rats used as a genetic control. These metabolic parameters gradually progressed with age. Likewise, the serum levels of oxidative stress markers, including lipid peroxides, which oxidatively modify low-density lipoprotein (LDL) and 8-hydroxydeoxyguanosine (8-OHdG), gradually increased in SHR/cp rats. The serum levels of 3-nitrotyrosine and 3-chlorotyrosine also persistently increased, indicating the involvement of peroxynitrite or myeloperoxidase-catalyzed oxidation. In addition, high-sensitivity C-reactive protein (hsCRP), an early marker of inflammation, temporarily increased in SHR/cp rats compared to WKY rats. These findings suggest that oxidative stress, as well as nitrative stress and inflammation, increases in the metabolic syndrome, which may contribute to the development of atherosclerosis.