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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Background: Methotrexate(Mtx) is an antineoplastic and immunosuppressive drug. That may cause hepatotoxicity, whereas quarcetin has anti-inflammatory and antiproliferativeproperties. Aim of the Work: This study aimed to investigate the possible protective and therapeutic effects of quercetin against methotrexate (Mtx)-induced hepatotoxicity with biochemical and histopathological studies in rats. Materials and Methods: Twenty four adult male wister albino rats were equally divided into four experimental groups: control(group I), Mtx group (group II) rats received (single dose of Mtx 20 mg/kg i.p.). QCT protective group (group III) rats pre-treated with QCT (20 mg/kg orally daily for 7 days before Mtx administration. QCT therapeutic group (group IV) rats cotreated with Mtx(20 mg/kg for i.p, single dose)thenQCT were given as before .Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using H&E, masson's, PCNA staining, and serum transaminases were measured and statistically compared across all groups. Results: Group II (Mtx group) demonstrated hydrobic degeneration of hepatocytes, congestion of hepatic sinusoids, central veins and portal veins .An apparent increase in collagenous fibers distribution around the central vein and portal tract was detected .In groups III (protected QCT), and group IV (QCT therapeutic groups), showed less histological injury compared to Mtx group as regards liver sections ,but pretreatment with QCT in group III was more effective and liver section appeared highly improved except for mild dilation of central vein and blood sinusoids. Conclusion:Methotrexate has a deleterious effect on the liver. Quaricetin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.