RESUMO
The protective effect of 5-HT(2) receptor blockade with ketanserin or ritanserin against cadmium liver injury was investigated. Male Wistar rats were injected intraperitoneally with a sublethal dose of cadmium (3.5 mg/kg body weight). Rats were treated with normal saline (group I), ketanserin (3 mg/kg body weight; group II), or ritanserin (3 mg/kg body weight; group III) 2 hr prior and 4 hr after cadmium administration and killed at different time points. Hematoxylin/eosin-stained liver sections were assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay. Nonparenchymal liver cells and activated Kupffer cells were identified histochemically. Necrosis, hepatocyte apoptosis, nonparenchymal cell apoptosis, and macroscopic and microscopic peliosis were markedly reduced or minimized in ketanserin- or ritanserin-treated rats. The observed protective effect was almost identical for both ketanserin and ritanserin administration. 5-HT(2) receptor blockade exerts a protective effect against acute cadmium-induced hepatotoxicity.
Assuntos
Ketanserina/uso terapêutico , Falência Hepática Aguda/tratamento farmacológico , Ritanserina/uso terapêutico , Antagonistas do Receptor 5-HT2 de Serotonina , Antagonistas da Serotonina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Modelos Animais de Doenças , Marcação In Situ das Extremidades Cortadas , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores 5-HT2 de Serotonina/metabolismo , Resultado do TratamentoRESUMO
UNLABELLED: The effect of serotonin receptor 2 blockade (5-HT(2)) on liver regeneration after 30-34% and 60-70% partial hepatectomy in the rat liver was investigated. MATERIALS AND METHODS: Male Wistar rats were subjected to 60-70% (group I) and 30-34% (group II) partial hepatectomy. Serotonin receptor 2 blockade was exerted by intraperitoneal administration of ketanserin at different doses and time points after partial hepatectomy. The rats of all groups were killed at different time points until 96 h after partial hepatectomy. The rate of liver regeneration was evaluated by the mitotic index in hematoxylin and eosin sections, the immunochemical detection of Ki67 and proliferating cell nuclear antigens, the rate of [(3)H]-thymidine incorporation into hepatic DNA and liver thymidine kinase enzymatic activity. RESULTS: Liver regeneration peaked at 24 and 32 h after partial hepatectomy in 60-70% hepatectomized rats. In 30-34% hepatectomized rats liver regeneration peaked at 60 h, whereas low rates of regenerative activity were observed between 24 and 72 h after partial hepatectomy. Ketanserin administration arrested liver regeneration only when administered at 16 h after 60-70% partial hepatectomy. Ketanserin also abrogated the observed peak of regenerative activity at 60 h in 30-34% hepatectomized rats when administered at 52 h after partial hepatectomy. All indices of liver regeneration were affected by ketanserin administration. CONCLUSIONS: Serotonin receptor 2 blockade can arrest liver regeneration only when administered close to G1/S transition point, and that while serotonin may be a cofactor for DNA synthesis, it does not play a role in initiation of liver regeneration.
