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.
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...
We designed this work to examine the curative role of L-carnitine (LCAR) in a rat model of cisplatin (CDDP)-induced kidney injury. We induced kidney injury in rats by a single intraperitoneal injection of 5 mg/kg of CDDP. Fifteen days post injection, rats were orally supplemented with 354 mg/kg of LCAR for another 15 days. Kidney tissues were subjected to histo-biochemical analysis along with mRNA gene expression quantification for cytoskeleton proteins encoding genes (vimentin, nestin, and connexin 43) by real-time reverse transcription polymerase chain reaction. LCAR reversed CDDP-induced renal structural and functional impairments. LCAR significantly declined serum urea and creatinine concentrations, restored oxidant/antioxidant balance, reversed inflammation, and antagonized caspase 3-mediated apoptotic cell death in renal tissues. Moreover, LCAR effectively down-regulated cytoskeleton proteins mRNA levels, reflecting amelioration of CDDP-provoked podocyte injury. We concluded that LCAR has a favorable therapeutic utility against CDDP-induced kidney injury.
We have assessed the effects of the broad‐spectrum bactericide triclosan on the liver of pregnant albino rats and their offspring, and evaluated the protective potential of bee honey, which has radical‐scavenging properties. The study involved treatment of 72 pregnant rats followed by examination of the pregnant rats and their offspring. The pregnant rats were divided equally into six groups (I–VI), each of which was subdivided equally into two Subgroups (A and B). Rats in the A subgroups were gavaged with a daily dose of 1.26 ml distilled water (IA), 1 ml corn oil (IIA), 1.68 ml aqueous solution of Clover Blossom honey (IIIA), 0.3 mg triclosan (IVA), 13 mg triclosan (VA), or 1.68 ml aqueous solution of honey with 13 mg triclosan (VIA), throughout pregnancy. Rats in the B subgroups received the same treatments throughout pregnancy and for 14 days after delivery. At the end of the experiments, the offspring's numbers were recorded and blood samples were taken from the pregnant rats for analysis. The livers of the studied groups were subjected for; histological study, morphometric analysis, and biochemical estimation of markers of oxidative stress. The results showed that the acceptable daily intake of triclosan did not induce significant pathological changes in the liver while high dose of triclosan induced pathological changes in the livers and reduced the numbers of offspring. Co‐administration of honey with triclosan ameliorated most pathological change. Therefore, decrease the exposure of the pregnant women to triclosan is encouraged or co‐supplementation with bee honey if exposure could not be avoided.
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