Abstract

Comparison between the effect of the thiazolidinedione-rosiglitazone-& the sulphonylurea -gliclazide- and their combination on the liver of streptozotocin-induced diabetes mellitus in rats.

Mohamed M. Ewais^1, Magda M Naim², Soha S. Essawy¹and

 Amani A. El-Baz³

Departments of Pharmacology¹, Histology ² and Physiology ³,

Faculty of Medicine, Suez Canal University.

Abstract

         This study was conducted to compare between the possible effects of rosiglitazone "A new oral antidiabetic drug with selective PPAR-gamma agonistic effect" in a dose of 0.03 mg/kg BW and gliclazide " An oral antidiabetic sulphonylurea" in a dose of 10 mg/kg BW either used alone or in combination, for 6 weeks on the liver, serum glucose and lipid profile in streptozotocin diabetic rats.

         Thirty rats were randomized into 5 groups (n=6). Group I; the control group was given saline orally daily for 6 weeks. Group II; the streptozotocin induced diabetic group. Group III received rosiglitazone, while group IV received gliclazide and group V received both drugs. 

The results of the present study revealed that streptozotocin significantly (P< 0.05) elevated serum glucose, cholesterol and triglycerides in rats compared to the controls. The insulin sensitizer "rosiglitazone" either alone or combined with gliclazide decreased serum glucose significantly (P< 0.05) compared to the diabetic group. Gliclazide alone also had the same effect. Rosiglitazone alone decreased serum cholesterol and AST and in combination with gliclazide decreased serum ALT significantly (P< 0.05) compared to the diabetic group.              

         For histopathological study, liver tissue was prepared for both histological (H&E, PAS & Masson’s trichrome) and immunohistochemical (alpha 1 antitrypsin expression) techniques.  Both qualitative and quantitative analysis was done to assess the degree of hepatic damage. According to certain criteria, H&E stained sections were quantitatively examined to assess the degree of hepatocyte affection, beside other quantitative measurements (optical density & color area percentage) using the image analyser.  Obtained results revealed that streptozotocin caused severe affection in 6% of hepatocytes, mild affection in 2% and moderate affection in 41%.  The drug also resulted in significant increase in PAS stained glycogen granules in hepatocytes as well as collagen in portal tracts.  Immunostaining of alpha 1 antitrypsin revealed increased expression in the lining of blood sinusoids including Kupffer cell cytoplasm and in the area around the central vein. Groups III, IV and V which were under the effect of rosiglitazone, gliclazide or both respectively, showed hepatocyte damage similar to that of diabetic control group; however the degree of that damage was only statistically significantly increased in case of group III. 

         When compared to diabetic control group, these groups (III, IV and V) showed no significant difference in both optical density of PAS positive reaction or mean color area percentage of collagen; however the mean optical density of immunostaining decreased significantly.      

         This indicated that rosiglitazone alone or when used concomitantly with gliclazide, in streptozotocin-induced diabetic rats resulted in improvement of their metabolic control, yet the potential of hepatotoxicity was still to be considered.

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