Planta Med 2004; 70(8): 745-752
DOI: 10.1055/s-2004-827206
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Anthocyanins Contained in a Blackberry Extract on the Circulatory Failure and Multiple Organ Dysfunction Caused by Endotoxin in the Rat

Lidia Sautebin1 , Antonietta Rossi1 , Ivana Serraino2 , Paola Dugo3 , Rosanna Di Paola2 , Luigi Mondello4 , Tiziana Genovese2 , Domenico Britti5 , Angelo Peli6 , Giovanni Dugo4 , Achille P. Caputi2 , Salvatore Cuzzocrea2
  • 1Dipartimento di Farmacologia Sperimentale, Università ”Federico II”, Napoli, Italy
  • 2Dipartimento Clinico e Sperimentale di Medicina e Farmacologia, Torre Biologica, Policlinico Universitario, Messina, Italy
  • 3Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Messina, Italy
  • 4Dipartimento di Chimica Organica e Biologica, Facoltà di Scienze MFN, Università di Messina, Messina, Italy
  • 5Department of Clinical Veterinary Science, University of Teramo, Italy
  • 6Department of Clinical Veterinary, Alma Mater Studiorum Bologna, Italy
Further Information

Publication History

Received: December 1, 2003

Accepted: May 15, 2004

Publication Date:
24 August 2004 (online)

Abstract

Anthocyanins are a group of naturally occurring phenolic compounds related to the colouring of plants, flowers and fruits. These pigments are important as quality indicators, chemotaxonomic markers and for their antioxidant activities. Here we have investigated the therapeutic efficacy of anthocyanins contained in a blackberry extract on (i) circulatory failure, (ii) multiple organ dysfunction and (iii) activity of the inducible isoforms of nitric oxide (NO) synthase (iNOS) and cyclooxygenase (COX-2) in anaesthetised rats with endotoxic shock. In a model of endotoxic shock induced by lipopolysaccharide (LPS, E. coli, 10 mg/kg, i. v.) in the rat, pretreatment with anthocyanins present in the blackberry extract (5 mg/kg, i. v. 30 min before LPS) prevented the hypotension induced by LPS. Endotoxaemia also caused rises in the serum levels of (i) glutamyl oxaloacetic transaminase (GOT), glutamyl pyruvic transaminase (GPT), alkaline phosphates and bilirubin (hepatic dysfunction) (ii) creatinine (renal dysfunction), (iii) amylase and lipase (pancreatic injury), (iiii) NOx and 6-keto-PGF1 α. Anthocyanins attenuated the hepatic and pancreatic injury, the renal dysfunction and decreased NOx and 6-keto-PGF1 α levels. Endotoxaemia for 6 h resulted in a substantial increase in iNOS and COX activity in rat lung, which was attenuated in rats pretreated with anthocyanins. Moreover, anthocyanins (0.02 - 0.32 mg/mL) inhibited in vitro iNOS and COX activity from lung of LPS-treated rats. Polymorphonuclear (PMN) infiltration (myeloperoxidase activity), lipid peroxidation (malondialdehyde levels) as well as tissue injury (histological examination) induced by LPS in rat lung and ileum was reduced by anthocyanins (5 mg/kg, i. v. 30 min before LPS). Furthermore, endotoxaemia induced the formation of nitrotyrosine and poly(ADP-ribose) synthetase (PARS) activation as determined by immunohistochemical analysis of lung and ileum tissues. The degree of staining was lowered by anthocyanin treatment. These results indicate that the anthocyanins contained in the blackberry extract exert multiple protective effects in endotoxic shock.

Abbreviations

NOx:nitrite/nitrate

LPS:lipopolysaccharide

NO:nitric oxide

iNOS:inducible nitric oxide synthase

COX-2:cyclooxygenase-2

PMN:polymorphonuclear

PARS:poly(ADP-ribose) synthetase

PG:prostaglandin

ROS:reactive oxygen species

MODS:multiple organ dysfunction syndrome

MAP:mean arterial blood pressure

GOT:glutamyl oxaloacetic transaminase

GPT:glutamyl pyruvic transaminase

DEX:dexamethasone

MPO:myeloperoxidase

MDA:malondialdehyde

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Dr. Salvatore Cuzzocrea

Dipartimento Clinico e Sperimentale di Medicina e Farmacologia

Torre Biologica

Policlinico Universitario

98123 Messina

Italy

Email: salvator@unime.it