title: Inhibition of tumor necrosis factor-alpha and cyclooxigenase-2 by Isatin: a molecular mechanism of protection against TNBS-induced colitis in rats.
abstract: Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE₂ levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.
authors: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 13083-887 Campinas, SP, Brazil. Electronic address: eduardo_socca@yahoo.com.br.
authors: Eduardo Augusto Rabelo
authors: EA
authors: Socca
authors: Departamento de Ciências Biológicas, Universidade Federal de Goiás (UFG), 75704-020 Catalão, GO, Brazil.
authors: Anderson
authors: A
authors: Luiz-Ferreira
authors: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 13083-887 Campinas, SP, Brazil.
authors: Felipe Meira
authors: FM
authors: de Faria
authors: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), 13083-865 Campinas, SP, Brazil.
authors: Ana Cristina
authors: AC
authors: de Almeida
authors: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 13083-887 Campinas, SP, Brazil.
authors: Ricardo José
authors: RJ
authors: Dunder
authors: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), 13083-865 Campinas, SP, Brazil.
authors: Luis Paulo
authors: LP
authors: Manzo
authors: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 13083-887 Campinas, SP, Brazil; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), 13083-865 Campinas, SP, Brazil.
authors: Alba Regina Monteiro Souza
authors: AR
authors: Brito
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007510:Isatin / Q000494:pharmacology*; D051381:Rats; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007510:Isatin; D014302:Trinitrobenzenesulfonic Acid; D051546:Cyclooxygenase 2; D005978:Glutathione
keywords: COX-2; Isatin; Myeloperoxidase; TNBS; TNF-α; Ulcerative colitis