Protective effects of indomethacin and cyclophosphamide but not of infliximab on liver metabolic changes caused by adjuvant-induced arthritis.
In the study, indomethacin, cyclophosphamide, and infliximab were administered to adjuvant-induced arthritic rats to determine if they were able to prevent the abnormalities caused by arthritis on hepatic metabolism. The drugs were administered to arthritic rats, and at the clinical onset of arthritis (day 14 after adjuvant injection), the livers were perfused to evaluate gluconeogenesis, ureagenesis, oxygen uptake, L: -lactate, pyruvate, and ammonia release from L: -alanine. The effects of the drugs on body weight gain and the signs of arthritis (paw edema, appearance of secondary lesions, and weights of lymphoid tissues) were also evaluated. Cyclophosphamide could completely prevent liver metabolic changes and the inflammatory response. Indomethacin restored ureagenesis, minimized the decrease in gluconeogenesis, and exerted a partially beneficial effect on inflammatory reactions. Infliximab did not improve arthritis-induced liver metabolic alterations or inflammatory responses. These results suggest the participation of prostaglandins, but not TNF-α, on arthritis-induced liver metabolic alterations.
da Silva
Maria Angélica Raffaini Covas Pereira
MA
Department of Pharmacy and Pharmacology, University of Maringá, Bloco K68-106, Avenida Colombo, 5790, CEP: 87020-900, Maringá, Paraná, Brazil.
Bersani-Amado
Ciomar Aparecida
CA
Ishii-Iwamoto
Emy Luiza
EL
Bracht
Lívia
L
Caparroz-Assef
Silvana Martins
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation; D000069285:Infliximab; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins; D020011:Protective Agents; D051381:Rats; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha
D000911:Antibodies, Monoclonal; D011453:Prostaglandins; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D000069285:Infliximab; D007213:Indomethacin