RESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the modulation of the inflammatory response. However, a number of facts involving the occurrence of gastrointestinal lesions have limited the chronic use of NSAIDs. In order to diminish the occurrence of gastrointestinal damage caused by NSAIDs, the combination of NSAIDs with the H2 receptor blocker, cimetidine, has been evaluated. The anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in association with or without cimetidine were determined at pre-clinical levels. It was observed that the group of animals treated with indomethacin and cimetidine, or tenoxicam and cimetidine (10 mg/kg, p.o.) demonstrated a significant reduction (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test) of type-III gastric ulcers. Furthermore, indomethacin or tenoxicam (10 mg/kg, p.o.) in association with cimetidine increased the anti-inflammatory activity. The group, which received indomethacin and cimetidine presented the best performance in decreasing the inflammatory process (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test).
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cimetidina/administração & dosagem , Indometacina/administração & dosagem , Piroxicam/análogos & derivados , Piroxicam/administração & dosagem , Úlcera Gástrica/induzido quimicamente , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Cimetidina/toxicidade , Quimioterapia Combinada , Edema/tratamento farmacológico , Indometacina/toxicidade , Masculino , Piroxicam/toxicidade , Ratos , Ratos Wistar , Úlcera Gástrica/classificaçãoRESUMO
The toxic effect of the hydroalcoholic crude extract (HACE) from the fruits of the Solanum grandiflorum was evaluated following subchronic treatment (p.o.) in Wistar rats for 65 days using the dose of 2 mg/kg. The LD(50) in mice was 50 mg/kg (p.o.). At the end of treatment, the consumption of water remained within the normal patterns. On the other hand, the consumption of food had 40% reduction in the period between the 18th and the 40th day after the beginning of the study. The diuresis showed a wide variation in volume which started at the 8th day of treatment until the end of the study. This finding was correlated with macroscopic observations of the kidneys which presented nephromegaly (70%) when compared to the control group. Moreover, for the histopathological study, it was observed degeneration and glomerular necrosis (100%), tubular lesions (80%), and hypercellular lesions (100%) in the treated group. The ponderal development of the treated group was increased compared to the control group. The weight of some of the organs, including kidneys, lungs, and pancreas, was also increased in the treated group (P<0.05, Student "t" test). These data suggest a nephrotoxicity following a subchronic treatment of the hydroalcoholic crude extract from Solanum grandiflorum.