title: Inhibition of advanced glycation end products by aminoguanidine restores mast cell numbers and reactivity in alloxan-diabetic rats.
abstract: Mast cell number and reactivity have been shown to be down-regulated under diabetic conditions. This study was undertaken in order to investigate the role of the advanced glycation end products in the reduction of mast cell number and reactivity in diabetic rats. The effect of aminoguanidine on mast cell apoptosis was also evaluated. Diabetes was induced by intravenous injection of alloxan into fasted rats and aminoguanidine was administered after 3 days of diabetes induction, once daily for 18 consecutive days. Mast cell apoptosis and levels of Bax, a pro-apoptotic member of Bcl-2 family, were evaluated by TUNEL and western blot, respectively. Diabetes led to increased levels of fructosamine and AGEs in the plasma, an effect prevented by aminoguanidine. Treatment with aminoguanidine restored mast cell numbers in the pleural cavity and in mesenteric tissue of diabetic rats. Aminoguanidine also significantly reversed the diabetes-induced reduction in histamine release, as measured by fluorescence, following activation with substance P or antigen in vitro. Increased apoptosis and levels of Bax in mast cells from diabetic rats were inhibited by aminoguanidine. In conclusion, our findings showed that aminoguanidine restored the number and reactivity of mast cells in diabetic rats, accompanied by suppression of apoptosis, evidencing that advanced glycation end product formation has a critical role in mast cell behavior of diabetic rats.
authors.affiliation: Laboratório de Inflamação, Fundação Oswaldo Cruz, Av. Brasil, no. 4365, Manguinhos, CEP 21045-900, Rio de Janeiro, Brazil.
authors.forename: Vinicius F
authors.initials: VF
authors.lastname: Carvalho
authors.forename: Luisa T
authors.initials: LT
authors.lastname: Florim
authors.forename: Emiliano
authors.initials: E
authors.lastname: de O Barreto
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Torres
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Batista
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Amendoeira
authors.forename: Renato S B
authors.initials: RS
authors.lastname: Cordeiro
authors.forename: Marco A
authors.initials: MA
authors.lastname: Martins
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: E Silva
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000097:blood / Q000276:immunology*; D006146:Guanidines / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D008643:Mesentery / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology; D035422:Pleural Cavity / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000276:immunology
chemical_list: D000941:Antigens; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007328:Insulin; D051028:bcl-2-Associated X Protein; D013373:Substance P; C004479:pimagedine