Antioxidant and anti-inflammatory effects of dimethyl fumarate in hypercholesterolemic rabbits

Abstract The present study aimed to determine the possible beneficial effects of dimethyl fumarate (DMF) against oxidative stress and inflammation in hypercholesterolemic rabbits. Twenty four New Zealand male rabbits were randomly allocated into 4 groups as the following: Group I (control): rabbits received standard rabbit chow; Group II high cholesterol diet (HCD): rabbits received 1% cholesterol-enriched chow for 4 weeks; Group III (HCD-DMF): rabbits received 1% cholesterol-enriched chow and administered DMF (12.5 mg/kg/day, orally) for 4 weeks; Group IV (DMF): rabbits received standard chow plus DMF (12.5 mg/kg/day, orally) for 4 weeks. At the end of experiment (day 30), blood samples were collected for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP). In addition, the aorta was removed for measurement of malondialdehyde (MDA), superoxide dismutase (SOD), mRNA expression of cholesteryl ester transfer protein (CETP) and histological assessment of intima/media (I/M) ratio. HCD-fed rabbits showed significant increases in TGs, TC, low-density lipoprotein cholesterol (LDL-C), aortic MDA and aortic I/M ratio levels while they significantly exhibited a reduced SOD level relative to control animals. Moreover, HCD rabbits demonstrated upregulated mRNA expression of CETP. DMF administration significantly decreased HCD-induced elevations in serum TC and LDL-C. Additionally, DMF decreased aortic level of MDA while increased SOD level. Moreover, DMF significantly downregulated mRNA expression of CETP and reduced the elevation in I/M ratio. In conclusion, this study suggests that DMF has the ability to improve HCD-induced vascular irregularities, possibly via its anti-inflammatory and antioxidant effect.