Modulation of gastrin and epidermal growth factor by pyrrolizidine alkaloids obtained from Senecio brasiliensis in acute and chronic induced gastric ulcers.
We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis. The PA extract demonstrated significantly activity in both, acute and chronic gastric ulcers on rats. The effects of PA extract were dose dependent. The mechanisms implicated on this activity were evaluated by determination of gastrin plasma levels in rats subjected to the acute treatment with PA extract and by expression of mRNA of Epidermal Growth Factor (EGF) after chronic treatment with this extract. The results showed that the PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF.
Toma
Walber
W
Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
Trigo
José Roberto
JR
Bensuaski de Paula
Ana Cláudia
AC
Monteiro Souza Brito
Alba Regina
AR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005755:Gastrins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D012674:Senecio; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D005755:Gastrins; D010936:Plant Extracts; D011763:Pyrrolizidine Alkaloids; D004815:Epidermal Growth Factor