ABSTRACT
Thirty two adult female albino rats were randomized into 2 main groups [control and experimental]. The control group [n=8] received IM injection of 0.3 ml of the drug vehicle [castor oil and benzyl benzoate] once every 5 days for 6 times. 50% of rats of this group were scarificed after 24 hours of the last injection while the other 50% were left for 15 days. Experimental group was divided into 2; experimental group 1; E1 [n=12] received IM injection of 1.5 mg/kg BW of the drug [Mesigyna], once every 5 days for 6 times, and were sacrificed 24 hours after the last injection. Experimental group 2; E2 [n=12] were injected as in group E1 then left for 15 days. Uterine tissue was used for various techniques; histological [H and E and Masson's trichrome] and immunohistochemical [staining of progesterone receptors, using Labeled-Streptavidin method]. Both qualitative and quantitative analyses were done to assess the degree of uterine affection. Quantitative measurements [optical density, color area percentage, line distance and cells count] were performed using the image analyzer. Mesigyna injection showed increased endometrial folding [91.6% of the animals] with decreased endometrial thickness. Luminal epithelium showed proliferation with pseudostratification of its nuclei [75% of animals], necrotic changes [31.3% of animals], hyperplasia [epithelial tufting; in 25% of animals] and desquamation [8.3% of animals]. Increased gland size and stromal hypercellularity were also observed. Polymorphonuclear cellular infiltration in both endometrium and myometrium, Vascular congestion and increased myometrial thickness were respectively seen in 83.33%, 63.5 %, 83.5% of E1 group animals. Mesigyna also caused reduction in the amount of collagen fibers. Immunostaining revealed decreased number and optical density of progesterone receptors in nuclei of surface epithelium, glandular epithelium and stromal cells while they were increased in nuclei of smooth muscle fibers. Image analysis results confirmed both the histological and the immunohistochemical results. After withdrawal of the drug [group E2], results showed reduction in necrotic changes, endometrial folding, epithelial tufting and hyperplasia. However there was an aggravation of Polymorphonuclear infiltration, vascular congestion and immunohistochemical changes which indicated delayed recovery of these changes in rat uterus under the effect of Mesigyna. In conclusion Mesigyna was found to produce severe histopathological changes which were not completely recovered after 15 days of drug stoppage
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 [HandE, PAS and 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, HandE stained sections were quantitatively examined to assess the degree of hepatocyte affection, beside other quantitative measurements [optical density and 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