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Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

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Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products.Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylin & eosin (H & E) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by H & E changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction.However, rats exposed to DBP alone showed no changes in either α or β-cells. Both combined-exposed animals displayed α and β apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in αcell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/β cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.

Background: Grape seed extract (GSE) is a powerful antioxidant containing high levels of bioflavonoids, vitamin C and vitamin E. The aim of the work is to study the possible protective and ameliorative effects of grape seed extract in an animal model of cadmium (Cd)-induced testicular toxicity in rats. Materials and Methods:A thirty-day oral gavage study in adult male albino rats was performed using 32 animals, randomly divided into 4 equal groups; negative control, cadmium (5 mg/k/day), grape seed extract (100 mg/k/day), and cadmium + GSE. Testicular weights were measured. Hematoxylin & eosin (H&E) staining and proliferating nuclear cell antigen (PCNA) immunohistochemistry, as a marker for proliferation were done. Morphometric parameters were assessed and subjected to statistical analysis. 2 Results: The H&E results showed atrophy and distortion of the seminiferous tubules (STs) with sloughing of the spermatogenic epithelium in cadmium group. The interstitial spaces were widened and showed edema and mononuclear cell infiltrations. No remarkable changes were observed in the grape-seed-only group when compared to the control group. In both combined group, maintaining of the STs and their lining cells was evident. The immunohistochemical results showed marked positive PCNA immunoreactivity in both control and GSE groups, while negative immunoreaction was noticed in Cd group. Limited positive PCNA immunoreactivity was ameliorated in Cd+ GSE group. Conclusions: GSE protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture.National Institutes of Health [9]. Whenever possible, the procedures in the current study were conducted to avoid or minimize suffering, distress, and pain to animals. DrugsCadmium, in the form of cadmium chloride (CdCl2, 96% pure), was purchased from Sigma-Aldrich Corporation of industrial chemistry and biotechnology (St. Louis, Missouri, USA). Grape seed extract was purchased from herbal and medicinal plant store, Benha governorate, Egypt. The drugs were dissolved in normal saline. Experimental designThe rats were randomly divided into four groups, eight rats each: -Group 1: Negative control group (normal saline was given daily for 30 days by gastric gavage)Group 2: The animals were given grape seed extract (100 mg/kg/d) dissolved in normal saline for 30 days by gastric gavage [32]. A concentration of 100 mg was dissolved in 10 ml normal saline and shook to obtain a solution of 10 mg/ml. Group 3:The animals were given cadmium (5mg/kg/d) dissolved in normal saline for 30 days by gastric gavage [14]. A concentration of 5mg was dissolved in 10 ml normal saline and shook to obtain a solution of 0.5 mg/ml. Group 4:The animals were given cadmium (5mg/kg/d) + grape seed extract (100 mg/kg/d) for 30 days by gastric gavage.In order to avoid possible drug interactions and drug absorption, the drugs were given in the same time of the day, in two different time intervals. Cadmium was given in the morning (10 AM) whil...

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