Drug repurposing: Metformin's effect against liver tissue damage in diabetes and prostate cancer model.

Background: There are evidences linking diabetes to the pathogenesis and progression of various cancers. Metformin is a well-known antidiabetic drug that reduces the levels of circulating glucose and insulin in patients with both insulin resistance and hyperinsulinemia. Aim of the present study was to evaluate the effect of metformin on the liver of rats bearing prostate cancer, diabetes and prostate cancer + diabetes via histopathological and biochemical methods. Methods: Male Copenhagen rats were divided into six groups. Control group, diabetic group, cancer group, diabetic + cancer group, diabetic + cancer + metformin group, cancer + metformin group. Diabetes was induced by injecting single dose of streptozotocin (65 mg/kg) to Copenhagen rats, cancer induced 2 × 104 Mat-LyLu cells. Metformin treatment was administered daily by gavage following inocculation of the Mat- Lylu cells to fifth and sixth group. The experiment was terminated on the 14th day following Mat-LyLu cell injection. At the end of the experimental period, the rats were sacrificed, and liver tissue was taken. Liver damage was scored. Biochemically, serum prostate-specific antigen level was determined by employing Enzyme Linked Immuno Sorbent Assay method. In addition, the activities of different enzyme and biochemical parameters were determined spectrophotometrically inform the hepatic tissue specimens. Results: The findings of this study reveal that histopathological and biochemical damage in cancer and diabetic + cancer groups decreased significantly in the metformin treated groups. Conclusion: These highlights that the antidiabetic drug metformin can be repositioned for attenuating liver tissue damage associated with prostate cancer and diabetes.

Lupeol inhibits pesticides induced hepatotoxicity via reducing oxidative stress and inflammatory markers in rats.

The present study was aimed at investigating the toxicity of various pesticides on rat liver. It also aimed to show whether this toxicity could be avoided using lupeol. Adult male Wistars albino rats were randomly divided into nine groups. Control groups were given saline, corn oil, and lupeol; pesticide groups were given malathion, chlorpyrifos, and tebuconazole; in the other three treatments, same doses of pesticides and lupeol were given to the rats for ten days. Histopathological examination showed severe degenerative changes in the pesticide groups. Serum AChE activities, liver GSH, total antioxidant capacity levels, AChE, CAT, SOD, GPx, GR, Na+/K+-ATPase, ARE, and PON were decreased, while serum TNF-α, liver LPO, HP, NO, AOPP, total oxidant status, ROS, and oxidative stress index levels as well as AST, ALT, ALP, GST, arginase and xanthine oxidase activities were increased in the pesticides administered groups. It was observed that the PCNA levels determined by the immunohistochemical method increased in the pesticide groups. Also, the results Raman spectroscopy suggest that the technique may be used to understand/have an insight into pesticide toxicity mechanisms. The administration of lupeol demonstrated a hepatoprotective effect against pesticide-induced toxicity.

Brain Boron Level, DNA Content, and Myeloperoxidase Activity of Metformin-Treated Rats in Diabetes and Prostate Cancer Model.

In this study, the effect of metformin on boron levels and oxidative brain damage in rats due to diabetes and prostate cancer was investigated for the first time. Myeloperoxidase (MPO) activity and the amount of DNA were investigated as tissue oxidative and toxic damage parameters. In Copenhagen rats, Dunning prostate cancer was induced using high metastatic MAT-Lylu cells and diabetes was induced by single dose of streptozotocin (STZ) injection. Metformin was administered for 14 days after diabetes and prostate cancer induced. The rats were divided into six groups as follows: control group, diabetic group (D), cancer group (C), diabetic + cancer (DC) group, cancer + metformin (CM) group, diabetic + cancer + metformin (DCM) group. At the end of the experiment, brains were removed. Significant decrease of brain boron levels and significant elevation of MPO activity and DNA levels were observed in D, C, and DC groups as compared to control group. The effect of diabetes induction on the brain boron levels was much more than prostate cancer induction. The administration of metformin with CM and DCM obviously declined MPO activity and increased brain boron levels almost near to control group level. In conclusion, this study shows that the protective effect of metformin against brain damage in STZ-induced diabetic rats with Dunning prostate cancer may also be related to increased boron levels. The boron levels may be a novel indicator of reduced toxic and oxidative stress. Furthermore, the distribution and mechanism of action of boron should be clarified.

Effects of microplastics and mercury on manila clam Ruditapes philippinarum: Feeding rate, immunomodulation, histopathology and oxidative stress.

Plastic pollution, which is one of the most important environmental problems at the present time, has been understood recently, and the effects of this pollution on ecosystem and biota are becoming a growing problem, especially in the aquatic ecosystems. Direct or indirect exposure to those particles leads to adverse effects on marine organisms. In the marine environment, plastic materials interact with other pollutants such as metals, thereby affecting the uptake levels of those pollutants in marine organisms. In the present study, the Manila clam Ruditapes philippinarum was exposed to polyethylene microbeads and mercury chloride in single, combined and incubated form at environmentally relative concentrations for one week in controlled laboratory conditions. The uptake and tissue distribution of both stressors as well as the vector role of microplastics on mercury uptake in the organisms were investigated. Filtration rates, biomarkers for immunomodulation and oxidative stress, and histological alterations were also evaluated. Microplastics were ingested by the clams, and translocated to the various tissues. However, contaminated microplastics displayed a negligible vector role in terms of mercury bioaccumulation in the clams. The single and interactive exposure of the stressors reduced the filtration rate in the clams. Both pollutants affected the immune system of the organisms. Histological alterations were determined in the gill and digestive gland tissues of the clams among the treatment groups, although oxidative stress biomarkers remained unchanged. This study suggests that the vector role of polyethylene microplastics in mercury uptake is negligible and reveals that the single and interactive one-week exposure of two pollutants induce toxicity in the manila clams.

The effects of combined alpha-tocopherol, ascorbic acid, and selenium against cadmium toxicity in rat intestine.

In this study, the effects of combined antioxidants treatment against cadmium toxicity were investigated microscopically, immunohistochemically, and biochemically in small intestine of Sprague Dawley rats. The rats were subdivided into four groups as intact control, cadmium was administrated, and both control and cadmium groups treated with ascorbic acid, alpha-tocopherol, and selenium. Metallothionein expression was localized in the base of intestinal glands in control rats and similar expression was observed with antioxidants treatment. In cadmium-administrated rats, metallothionein expression was detected in surface epithelium, longitudinal muscle layer, meissner, and myenteric plexuses, but not in the base of intestinal gland. On the other hand, in the rats treated with antioxidants and cadmium, immunreactivity increased in the surface epithelium and in the base of intestinal glands according to cadmium-administrated rats but not changed in the plexuses and longitudinal muscle layer. Biochemically, lipid peroxidation levels increased and glutathione levels decreased significantly in intestine of the cadmium group compared to the control. Treatment with antioxidants in cadmium-administrated rats led to a decrease in lipid peroxidation levels and a significant increase in glutathione levels. As a result, the combination of ascorbic acid, alpha-tocopherol, and selenium shows a protective effect against cadmium toxicity in small intestine.