Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats: Comparison with the antioxidant N‐acetylcysteine

Abstract

Hyperglycemia‐induced oxidative stress plays a critical role in the development of diabetic metabolic complications including hypertriglyceridemia. The beta isoform of Protein kinase C (PKCβ) is over‐expressed in various organs of diabetic rodents and can cause or exacerbate oxidative stress by activating NADPH oxidase, a major source of superoxide production in the cardiovascular system. We postulated that selective PKCβ inhibition with ruboxistaurin (RXT) may attenuate hypertriglyceridemia in diabetes by reducing oxidative stress. Control or streptozotozin‐induced diabetic rats were either untreated (C, D) or treated with RXT (1 mg/kg/day, D+RXT) or with the antioxidant N‐acetylcycsteine (NAC) (1.5g/kg/day, D+NAC) delivered by oral gavage for four weeks. Levels of 15‐F2t‐isoprostane (IsoP), a specific marker of oxidative stress, were significantly increased in D group in both the myocardium and plasma. This was accompanied by a marked increase in plasma triglycerides (P<0.05 vs. C). RXT and NAC, respectively, prevented the increase of IsoP and significantly attenuated the increases of triglycerides. However, triglycerides in the D+NAC group was lowered further than that in the D+RXT group (P<0.05). Despite similar antioxidant properties, ruboxistaurin seems to be inferior to NAC in reducing hypertriglyceridemia in diabetes.Supported by RGC/GRF grants (781109 M to ZX, 766709 M to MGI).