Involvement of MT2 receptors in protective effects of melatonin against cisplatin-induced gastrointestinal damage in mice
Braz. J. Pharm. Sci. (Online)
;
58: e20476, 2022. graf
Artigo
em Inglês
| LILACS
| ID: biblio-1403722
ABSTRACT
Abstract Melatonin (MLT) reportedly reduces side effects associated with certain antineoplastic agents. Accordingly, we investigated the effect of MLT on cisplatin (CP)-induced gastric emptying (GE) delay. Mice were intraperitoneally pretreated with vehicle (ethanol 5%; control group), MLT (5, 10, or 20 mg/kg), or N-acetylcysteine (NAC; 150 mg/kg), followed by CP treatment (5 mg/kg). Pharmacological modulation was analyzed using relevant receptor antagonists (luzindole non-selective MT1/MT2 antagonist; 5 mg/kg or 4-P-PDOT selective MT2 antagonist; 4 mg/kg) before treatment with MLT plus CP. All treatments were performed once daily for three days. GE was assessed using phenol red. Gut morphology was examined using scanning electron microscopy and optical microscopy. Compared with the control, CP decreased GE. Pretreatment with NAC and MLT (5 and 10 mg/kg) did not prevent CP-induced gastric dysmotility; however, pretreatment with 20 mg/kg MLT prevented this effect. In addition, luzindole and 4-P-PDOT suppressed MLT-mediated gastroprotection against cytotoxic effects of CP. CP caused degeneration of the gut mucosa, which was attenuated by MLT treatment. Thus, 20 mg/kg MLT prevented the GE delay and decreased CP-induced adverse effects on the gut mucosa. In addition, the gastroprotective activity was mediated via the MT2 receptor.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Receptor MT2 de Melatonina
/
Gastroenteropatias
/
Melatonina
Limite:
Animais
Idioma:
Inglês
Revista:
Braz. J. Pharm. Sci. (Online)
Assunto da revista:
Farmacologia
/
Teraputica
/
Toxicologia
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Federal University of São Francisco Valley/BR
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