Elif Taslidere

Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats

In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin–eosin (H-E), periodic acid Schiff and Masson’s trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.

Protective and Therapeutic Effect of Apocynin on Bleomycin-Induced Lung Fibrosis in Rats

We aimed to investigate the preventive and therapeutic effect of apocynin (APO) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; APO group, 20 mg/kg APO was given intraperitoneal for 29 days; BLC-1 and BLC-2 groups, a single intratracheal injection of BLC (2.5 mg/kg); APO+BLC-preventive group, 20 mg/kg APO was administered 12 h before the intratracheal BLC injection and continued for 14 days; BLC+APO-treatment group, 20 mg/kg APO was given on the 14th day after the intratracheal BLC injection and continued to sacrifice. The BLC-1 group was sacrificed on the 14th day of BLC administration to validate BLC-induced lung inflammation and fibrosis on the 14th of study initiation. All other groups were sacrificed on the 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity, total oxidant status (TOS), and oxidative stress index (OSI) were measured. An addition to the serum myeloperoxidase (MPO), the cell count and cytokines (IL-1β, IL-6, and IL-8) of bronchoalveolar lavage (BAL) fluid were assayed. BLC-provoked histological changes were significantly detected compared to the control group. APO restored these histological damages in different quantity in the treatment and prevention groups. BLC caused a significant decrease in GSH, CAT, and GPX, which were accompanied with significantly the increased MDA, TOS levels, and OSI in the lung tissue concomitant with increased levels of the cellular account and proinflammatory cytokines in the BAL fluid. Otherwise, APO administration, both before and after BLC, reversed all biochemical markers and cytokine as well as histopathological changes induced by BLC. Interestingly, APO treatment reversed MPO activity in serum increased by BLC. In this study, both protective and therapeutic effects of APO against BLC-induced lung fibrosis were demonstrated for the first time.

Aminoguanidine mitigates apoptosis, testicular seminiferous tubules damage, and oxidative stress in streptozotocin-induced diabetic rats.

This study aimed to investigate the effect of aminoguanidine (AG) against testicular damage streptozotocin (STZ) induced diabetes. Thirty two rats were separated into four groups: control, AG, STZ and STZ+AG. In the STZ group, 12.5±1.3% of tubules were seen as containing sloughed spermatogenic cells into the lumen, 28.7±1.8% of tubules were atrophic, 46.2±2.1% of tubules were degenerative and 8.5±0.9% of tubules contained giant cells. Statistically, the affected tubule number was significantly lower in the STZ+AG group than in the STZ group. Intensely stained caspase-3 cells showed a statistically significant increase in the STZ group, while it decreased in the STZ+AG group. The enzyme activities of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) level decreased and the level of malondialdehyde (MDA) and nitric oxide (NO) increased in the STZ group, while AG treated diabetic rats showed an increase of CAT, SOD activity and GSH level and a decrease in MDA and NO levels. This study shows that the oxidative stress, increased NO level and apoptotic cell death play an important role in diabetic rat testicular damage and that AG treatment of diabetic rats results in protection of spermatogenic cells against oxidative stress and apoptotic cell death.

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats

ABSTRACT Introduction: Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. Material-Metods: Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Massons trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. Results: The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). Conclusion: In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.

BACKGROUND/PURPOSE In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. METHODS Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. RESULTS Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively). CONCLUSIONS Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals.

Ameliorative effects of aminoguanidine on rat aorta in Streptozotocin-induced diabetes and evaluation of α-SMA expression.

OBJECTIVE Diabetes mellitus is one of the chronic metabolic diseases which is characterized by microvascular and macrovascular complications. This study was designed to investigate the improving the effects of amnioguanidine on aortic damage in a streptozotocin (STZ) induced diabetic rat model. METHODS Thirty-two male Sprague-Dawley rats divided into four groups as follows: Control, Aminoguanidine, Diabetes, and Diabetes+Aminoguanidine. Experimental diabetes was induced by single dose STZ (45 mg/kg) intraperitoneally. After administration of STZ, the DM+AMG group began to receive AMG (1 g/L) was prepared by dissolving in tap water during 10 weeks. At the end of the study, blood glucose levels were determined and rats were sacrified by ketamine anesthesia. Following routine tissue process, aortas were embedded in paraffin. Histochemical (H-E and Orcein) and immunohistochemical α-smooth muscle actin (α-SMA) stains were applied and the sections examined by light microscope. Statistical analysis was carried out using the SPSS 13.0 statistical program. RESULTS The rats in diabetes group had significantly higher blood glucose levels than the rats of control. The main histological alterations were detected in tunica media such as extensive thickening (414.32±9.62 μm), irregular of elastic fibers and intensive α-SMA staining in diabetic rats. The thickness of tunica media was statistically increased in DM group, when compared with the control group (p<0.001). On the other hand, AMG prevented disorganization of elastic fibers and overexpression of α-SMA. The mean thickness of tunica media was decreased significantly in DM+AMG (319.16±6.53 μm) compared with the DM group (p<0.001). CONCLUSION Our results demonstrate that AMG treatment may protect the impairment of aort structure at histological level.

Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats A histological and biochemical study

Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg−1 day−1 gavage for 21 days), ciprofloxacin (20 mg kg−1 twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman’s space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.

Evaluation of the cardiovascular effects of varenicline in rats.

Background Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events. Objective To determine the cardiovascular toxicity induced by varenicline in rats. Materials and methods We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 μg/kg/day varenicline on days 1–3, 9 μg/kg twice daily on days 4–7, and 18 μg/kg twice daily on days 8–90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed. Results Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups. Conclusion Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation.

Assessment of the biocompatibility of mineral trioxide aggregate, bioaggregate, and biodentine in the subcutaneous tissue of rats

OBJECTIVE The objective of this study was to evaluate the tissue inflammation caused by three endodontic repair materials. MATERIALS AND METHODS The materials included micro mega-mineral trioxide aggregate (MM-MTA), bioaggregate (BA), and biodentine (BD), which were implanted into the subcutaneous tissue of rats. The tissue samples for histological examination were prepared. The infiltration of lymphocytes and macrophages into the tissue was examined to assess the inflammatory response. RESULTS Lymphocyte infiltration: A significant increase was detected in the MM-MTA and BA groups on the 7th and 14th days as compared with the control (7th day P=0.0001, 14th day P=0.0176). There was no difference between the groups on the 45th day (P=0.1730). Lymphocyte infiltration had decreased over time in all groups. Macrophage infiltration: There was a significant increase by the 7th day in the test groups as compared to the control group (P=0.007). However, there was no difference between the experimental groups on the 14th (P=0.2708) and 45th (P=0.1291) days. CONCLUSION While MM-MTA and BA showed a similar biocompatibility, BD was more biocompatible than MM-MTA and BA in the 1 st week of the experiment. However, there was no difference between the materials at the end of the 45th day. MM-MTA, BA, and BD can be considered suitable endodontic repair materials.

The effects of pentoxifylline and caffeic acid phenethyl ester in the treatment of d-galactosamine-induced acute hepatitis in rats:

The aim of this study was to investigate histological changes in hepatic tissue and effects of pentoxifylline (PTX) and caffeic acid phenethyl ester (CAPE) on these changes using histochemical and biochemical methods in rats, in which hepatitis was established by d-galactosamine (d-GAL). Rats were divided into five groups as follows: control group, d-GAL (24 h) group, d-GAL group, d-GAL + PTX group, and d-GAL + CAPE group. In histological evaluations, the control group showed normal appearance of the liver cells. However in the d-GAL groups, focal areas consisting of inflammatory, necrotic, and apoptotic cells were detected in parenchyma. Glycogen loss was observed in the hepatocytes localized at the periphery of lobule. It was found that number of mast cells of portal areas were significantly higher in d-GAL groups compared with other groups (p = 0.0001). In addition, the number of cells with positive staining by Ki-67 and caspase-3 were significantly increased in GAL groups compared with the control group (p = 0.0001). In biochemical analysis, there was an increase in malondialdehyde and myeloperoxidase levels, while a decrease was observed in glutathione level and glutathione peroxidase activity in groups treated with d-GAL compared with the control group. On the other hand, it was seen that, in the groups treated with d-GAL, histological and biochemical injuries in the liver were reduced by administration of PTX and CAPE. In this study, we demonstrated the ameliorative effects of PTX and CAPE on d-GAL-induced liver injury.