Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics

Abstract

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.

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

“…In addition to its ability to stimulate insulin release from the pancreas, G has shown beneficial extra-pancreatic effects such as anti-oxidant and anti-inflammatory properties, which are also desirable for T1D (Rakel et al, 2007). Recent studies in our laboratories have shown that, when incorporated with a primary bile acid, G exerted a moderate but significant hypoglycemic effect in a rat model of T1D (Al-Salami et al, 2012), which was hypothesized to be due to the bile acid optimizing the absorption of G in the lower part of the gastrointestinal tract (GIT) (Al-Salami et al, 2008b). In another study, we showed that the hypoglycemic effect of G in T1D rats may have been caused by metabolites or secondary or tertiary conformation of the co-administered bile acid (Al-Salami et al, 2008e).…”

Probiotics Applications in Autoimmune Diseases

“…Thus, gut microflora in each individual, works as a finger print and exerts a significant control over the immune response to various 'antigenic' stimuli. In addition to the gut microfloral control on the intestinal immunoregulatory system and the mucosal barrier, it is also involved in the pathogenesis of symptoms related to metabolic interactions of the microflora with intestinal contents or intestinal functions such as peristaltic movement [25,26,[42][43][44]. As a result, many gastrointestinal disorders can be benefited from probiotic treatments.…”

“…Many ADs have been characterized by a compromised gut movement which has been linked to the disturbed immune system and can result in substantial gut bacterial and yeast overgrowth [20][21][22][23][24]. Such an overgrowth is postulated to disturb body physiological and biochemical reactions and exacerbate the autoimmune-associated inflammation.…”

Potentials and Limitations of Bile Acids and Probiotics in Diabetes Mellitus

“…Other mechanisms involve bile salts' effect on efflux and afflux protein transporters on the cell wall of various tissues including gut enterocytes, hepatocytes, nasal mucosa and others (AlSalami et al 2008c;Al-Salami et al 2008d;Al-Salami et al 2009a). …”