The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the rat heart following LPS challenge

Oxidative damage plays a key role in septic shock induced by lipopolysaccha ride (LPS) which is known to enhance the formation of reactive oxygen speci es (ROS). In this study, biochemical parameters indicative of oxidative str ess were tested in the rat heart following LPS challenge, with and without pretreatment with the antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant isolated and purified from spinach and its mai n components are flavonoids and coumaric acid derivatives. Treatment with L PS alone significantly (P < 0.05) increased the malondialdehyde (MDA) level in heart, both in cytosolic and mitochondrial fractions by 1.5- and 2.4-fo ld, respectively, and in plasma (2.66 fold). In the heart homogenate, the l evel of hydroperoxides also increased significantly (P < 0.05). In addition , LPS treatment significantly (P < 0.05) increased NADPH oxidase activity i n the heart microsomal fraction by approximately 10-fold compared to contro l. Pretreatment for 7 days with either apocynin or NAO prior to the LPS cha llenge significantly (P < 0.05) improved rat survival, decreased MDA levels in both fractions and decreased microsomal NADPH-oxidase activity, compare d to LPS alone. Catalase (CAT) activity slightly increased at 24 h post-LPS injection in LPS group and returned to the control level in the apocynin t reated group. No meaningful changes were indicated for glutathione peroxida se activity among all the treatment groups. The activities - of cytosolic a nd mitochondrial superoxide dismutase (SOD) enzymes significantly (P < 0.05 ) increased approximately 20% in the LPS-treated group, compared to control . Apocynin significantly (P < 0.05) decreased SOD level in the mitochondria l fraction with no effect on the cytosolic fraction; whereas, NAO had no im portant effect on SOD level in both fractions. The beneficial pretreatment effects of the antioxidants against oxidative stress in the rat heart prese nted in this study may suggest a potential chemopreventive effect of this c ompound in sepsis prevention. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.