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

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Abstract

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.

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Acknowledgments

We thank Kerstin Wilhelm and Minhong Wang for outstanding technical assistance. The study was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) MA 1119/3-3.

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Authors and Affiliations

  1. Department of Trauma, Hand and Reconstructive Surgery, Hospitals of the Goethe-University Frankfurt am Main, 60590, Frankfurt, Germany

    Borna Relja, Eva Töttel, Lara Breig, Dirk Henrich, Ingo Marzi & Mark Lehnert

  2. HealthEcon AG, 4051, Basle, Switzerland

    Heinz Schneider

Authors
  1. Borna Relja
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  2. Eva Töttel
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  3. Lara Breig
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  4. Dirk Henrich
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  7. Mark Lehnert
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Correspondence to Borna Relja.

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Relja, B., Töttel, E., Breig, L. et al. Plant polyphenols attenuate hepatic injury after hemorrhage/resuscitation by inhibition of apoptosis, oxidative stress, and inflammation via NF-kappaB in rats. Eur J Nutr 51, 311–321 (2012). https://doi.org/10.1007/s00394-011-0216-1

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