Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics.
The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.
Al-Salami
H
H
School of Pharmacy, University of Otago, Dunedin, New Zealand. hani.al-salami@stonebow.otago.ac.nz
Butt
G
G
Tucker
I
I
Mikov
M
M
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000496:Alloxan; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005907:Gliclazide / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D010539:Permeability; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018528:ATP-Binding Cassette Transporters; D000496:Alloxan; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D005907:Gliclazide; D007004:Hypoglycemic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C423013:Abcc2 protein, rat; C530580:sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate; C114462:multidrug resistance-associated protein 3