Aldose reductase inhibitor zopolrestat restores allergic hyporesponsiveness in alloxan-diabetic rats.
This study was undertaken to investigate the role of the aldose reductase in the refractoriness of diabetic rats to allergic inflammation. Wistar rats were actively sensitized with a mixture of Al(OH)3 plus ovalbumin and intrapleurally challenged with ovalbumin, 14 days later. Diabetes was induced by intravenous injection of alloxan into fasted rats, 7 days before sensitization, and the aldose reductase inhibitor zopolrestat was administered after 3 days of diabetes induction, once a day during 18 consecutive days. The treatment with zopolrestat restored antigen-induced protein extravazation and mast cell degranulation in the pleural cavity of diabetic sensitized rats. Zopolrestat also significantly reversed the suppression in the increase of total and specific levels of serum immunoglobulin E (IgE) noted in sensitized animals under conditions of diabetes. In addition, we noted that the drop in the pleural mast cell numbers as well as the increase in serum corticosterone levels in diabetic rats were inhibited by the drug. Our findings show that zopolrestat restored the hyporesponsiveness of diabetic rats to antigen provocation, in parallel with impairment of alloxan-induced mast cell depletion and hypercorticolism, indicating that polyol pathway activity seems to play an important role in these phenomena.
Carvalho
Vinicius F
VF
Laboratório de Inflamação, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, no 4365, Manguinhos, CEP 21045-900, Rio de Janeiro, Brazil.
Barreto
Emiliano O
EO
Serra
Magda F
MF
Cordeiro
Renato S B
RS
Martins
Marco A
MA
Fortes
Zuleica Bruno
ZB
e Silva
Patrícia M R
PM
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000496:Alloxan; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D010793:Phthalazines / Q000494:pharmacology*; D035422:Pleural Cavity / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D052160:Benzothiazoles; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007328:Insulin; D010793:Phthalazines; D011506:Proteins; C067172:zopolrestat; D000536:Aluminum Hydroxide; D000496:Alloxan; D010047:Ovalbumin; D000449:Aldehyde Reductase; D003345:Corticosterone