Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers

Abstract

Metabolic syndrome (MS) is recognized as a clinical-pathological entity, where central obesity and insulin resistance/compensatory hyperinsulinemia are the pathophysiological triggers of this disease. It has been determined that in MS a state of low-grade systemic inflammation is generated. It is characterized by the abnormal production of proinflammatory cytokines associated with an oxidative stress (OS) state secondary to the inflammatory process that leads to a systemic redox alteration affecting different targets. There are no studies of drugs that act on this state, therefore it was decided to evaluate the possible therapeutic responses of atorvastatin and metformin, first-line drugs used in states of hyperlipidemia and hyperglycemia respectively. Objective: to study the pharmacological action of atorvastatin and metformin, and its effects on OS markers in experimental MS.

32 adult Wistar male rats of average weight 280±20 g were used, divided into (A) Control (n=8), (B) MS (n=8), (C) MS+atorvastatin (n=8), (D) MS+metformin (n=8). MS was induced with 10% fructose in drinking water for 6 weeks, then 0.035mg/day atorvastatin and 1.78mg/day metformin was administered for 45 days with noxa persisting. Serum OS markers: Nitric oxide(NO)(μM), superoxide dismutase (SOD) (U/ml) quantified by spectrophotometry and myeloperoxidase (MPO)(U/mg) quantified by ELISA. Statistics: Bonferroni and Hotelling as post hoc test, significance p<0.05.

NO significantly decreased in group (B)(14.76±4.43) compared to (A)(26.01±2.78), and a significant increase was demonstrated in (C)(25.08±3.06) and in (D)(22.20±3.26) with respect to (B)(p<0.001). When analyzing the activity of SOD, a significant increase was observed in (B)(178.64±23.70) respect to (A)(135±12.25), and a significant decrease in (C)(145.71±25.41) in relation to (B)(p<0.01); no differences were found in (A) vs (C). MPO presented a similar behavior in (B)(181.30±12.06) when compared to (A)(116.07±10.32); (D)(113.07±14.90) on the other hand, evidenced a significant decrease when compared to (B)(p<0.01).

In SM a state of EO is evidenced by demonstrating an increase in SOD and MPO and a decrease in the bioavailability of NO in relation to control. Atorvastatin showed a regression of the prooxidative state evidenced by a normalization in the levels of NO and SOD, probably related to its pleiotropic effects. Regarding the group with metformin, there was restitution in the bioavailability of NO and decrease in MPO, this could be related to an anti-inflammatory action of the drug.