VOL. 4, No. 2, July 2008

H. Al-Salami, et al. [2008] Med. Hypotheses Res. 1: 93‒101.

Probiotic Treatment Proceeded by a Single Dose of Bile
Acid and Gliclazide Exert the Most Hypoglycemic Effect
in Type 1 Diabetic Rats

Hani Al-Salami*, Grant Butt, Ian Tucker, Ranko Skrbic,
Svetlana Golocorbin-Kon and Momir Mikov

New Zealand's National School of Pharmacy (H.A-S., I.T., M.M), Department of Physiology
(G.B.), and Department of Pharmacology (R.S., S.G.K.), University of Otago, Dunedin 9054,
New Zealand

Abstract. Probiotics have beneficial effects in treating diabetes and may form a useful
adjunct to established hypoglycemic drugs. Here we report the effect of pre-treatment with
probiotics followed by the oral administration of gliclazide + MKC (a semisynthetic bile
acid), on blood glucose levels (BGL) and gliclazide pharmacokinetics in a rat model of type 1
diabetes (T1D). Male Wister rats were randomly divided into 8 groups (N = 10), 4 of which
were made diabetic by i.v. injection of alloxan. Groups 1‒4 were administered a single dose
of gliclazide + MKC (20 and 4 mg/kg, respectively) by oral gavage while groups 5‒8 by i.v.
Group 1 was healthy while group 2 was diabetic. Groups 3 (healthy) and 4 (diabetic) were
gavaged with probiotic mixture for three days and 12 h after the last ingestion of probiotics,
a baseline blood sample was taken from all 8 groups of rats and gliclazide + MKC was
administered. Blood samples collected prior to gliclazide revealed probiotic treatment
significantly reduced BGL in diabetic rats which were further reduced after gliclazide + MKC
oral dose. Moreover, in probiotic treated healthy rats, gliclazide bioavailability was the
lowest. In contrast, in probiotic treated diabetic rats, gliclazide bioavailability was higher
than untreated diabetic rats. Probiotic treatment lowers BGL and increases gliclazide
absorption in this model of T1D. Our results suggest that a multidrug approach to treating
diabetes can prove useful with MKC, gliclazide and probiotics being potential adjuvant

Correspondence: Dr. Hani Al-Salami, New Zealand's National School of Pharmacy,
University of Otago, Level 6, Adams Building, 18 Frederick Street, PO Box 913, Dunedin
9054, New Zealand. Tel: 64 3 479 5285. Fax: 64 3 479 7034.

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