title: Effect of anthocyanins contained in a blackberry extract on the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat.
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), (iii) NOx and 6-keto-PGF1 alpha. Anthocyanins attenuated the hepatic and pancreatic injury, the renal dysfunction and decreased NOx and 6-keto-PGF1 alpha 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.
authors.affiliation: Dipartimento di Farmacologia Sperimentale, Università "Federico II", Napoli, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Paola
authors.initials: P
authors.lastname: Dugo
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Luigi
authors.initials: L
authors.lastname: Mondello
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Angelo
authors.initials: A
authors.lastname: Peli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dugo
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D004731:Endotoxins; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005638:Fruit; D007082:Ileum / Q000473:pathology; D007527:Isoenzymes / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy*; D019001:Nitric Oxide Synthase / Q000097:blood / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D029800:Vaccinium myrtillus
chemical_list: D000872:Anthocyanins; D004731:Endotoxins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases