Plant polyphenols attenuate hepatic injury after hemorrhage/resuscitation by inhibition of apoptosis, oxidative stress, and inflammation via NF-kappaB in rats.

PURPOSE: Oxidative stress and inflammation contribute to hepatic injury after hemorrhage/resuscitation (H/R). Natural plant polyphenols, i.e., green tea extract (GTE) possess high anti-oxidant and anti-inflammatory activities in various models of acute inflammation. However, possible protective effects and feasible mechanisms by which plant polyphenols modulate pro-inflammatory, apoptotic, and oxidant signaling after H/R in the liver remain unknown. Therefore, we investigated the effects of GTE and its impact on the activation of NF-kappaB in the pathogenesis of hepatic injury induced by H/R. METHODS: Twenty-four female LEWIS rats (180-250 g) were fed a standard chow (ctrl) or a diet containing 0.1% polyphenolic extracts (GTE) from Camellia sinensis starting 5 days before H/R. Rats were hemorrhaged to a mean arterial pressure of 30 ± 2 mmHg for 60 min and resuscitated (H/R and GTE H/R groups). Control groups (sham, ctrl, and GTE) underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested. RESULTS: Plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased 3.5-fold and fourfold, respectively, in vehicle-treated rats as compared to GTE-fed rats. Histopathological analysis revealed significantly decreased hepatic necrosis and apoptosis in GTE-fed rats after H/R. Real-time PCR showed that GTE diminished gene expression of pro-apoptotic caspase-8 and Bax, while anti-apoptotic Bcl-2 was increased after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as systemic IL-6 level and hepatic IL-6 mRNA were markedly reduced in GTE-fed rats compared with controls after H/R. Plant polyphenols also decreased the activation of both JNK and NFκB. CONCLUSIONS: Taken together, GTE application blunts hepatic damage, apoptotic, oxidative, and pro-inflammatory changes after H/R. These results underline the important roles of JNK and NF-kappaB in inflammatory processes after H/R and the beneficial impact of plant polyphenols in preventing their activation.

Effects of green tea catechins on the pro-inflammatory response after haemorrhage/resuscitation in rats.

Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism.