Hydroxychloroquine attenuated motor impairment and oxidative stress in a rat 6-hydroxydopamine model of Parkinson's disease.

PURPOSE: Parkinson's disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood-brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats. METHODS: Wistar rats were randomly divided into sham, PD, PD + levodopa and PD + HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo's tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels and α-synuclein protein expression in the SN were also measured. RESULTS: The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. In addition, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity. CONCLUSION: According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.

Evaluation of the Effect of Two Different Systemic Doses of Viola Odorata on Prevention of Induced Tongue Dysplasia in Rats.

STATEMENT OF THE PROBLEM: Oral cancer is among the ten most common cancers worldwide. It affects the life quality of patients in many ways. PURPOSE: The aim of this study was to compare the effects of two different systemic doses of Viola Odorata syrup on the prevention of 4-Nitroquinoline-1-oxide (4-NQO) induced tongue dysplasia in rats. MATERIALS AND METHOD: Forty-eight male Wistar rats were divided into four groups of A, B, C and D. Group A served as the control group. The rats in groups B to D received 30 ppm of 4-NQO in drinking water for 12 weeks. Additionally, the rats in groups B and C received Viola Odorata syrup at doses of 15 and 5 ml/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. RESULTS: The mean body weight of the rats in groups B, C, and D were lower than that in group A (p< 0.01). After 12 weeks of treatment, microscopically no histological changes of the tongue base epithelia were observed in the control group. The rats in group B did not show severe dysplastic changes; only mild to moderate histological changes including hyperplasia and hyperkeratosis were evident. These incidences were significantly more apparent in groups C with moderate to severe changes (p< 0.05) and group D with severe dysplastic changes (p< 0.01). Almost all rats in group D had hyperplasia and manifested all of the stages of dysplasia. CONCLUSION: Viola Odorata extract has dose-dependent inhibitory effects on the development of tongue induced dysplasia.

Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress.

BACKGROUND: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. METHODS: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. RESULTS: MTX significantly induced liver damage (P<0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). CONCLUSION: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extract's antinflammatory activity.

Effect of ground black seeds (Nigella sativa L.) on renal tubular cell apoptosis induced by ischemia/reperfusion injury in the rats.

OBJECTIVES: The aim of this study was to evaluate the effects of ground black seeds on renal tubular cell apoptosis following ischemia/reperfusion (I/R) injury in rats. MATERIALS AND METHODS: Forty male Wistar rats were randomly allocated into 5 equal groups including Sham, I/R model and three I/R+ black seeds (5, 10 and 20%)-treated groups. I/R groups' kidneys were subjected to 60 min of ischemia followed by 24 h of reperfusion. Microscopically, apoptosis of tubular cells was assessed by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) method. RESULTS: The apoptotic cells of renal tubules were increased significantly (P<0.01) in I/R group than those in sham operation group. The TUNEL positive cells in black seeds (10% and 20%) treatment groups decreased significantly (P<0.05). CONCLUSION: Inhibition of apoptosis may be responsible for the protective effects of black seeds in rats with renal I/R injury.

Protective effect of turmeric extract on ethotrexate-induced intestinal damage and oxidative stress.

AIM: The most important side effect of methotrexate (MTX) is mucositis. The purpose of this study was to evaluate the effect of turmeric extract on intestinal damage and oxidative stress in rats receiving methotrexate. METHODS: Experiments were performed on male Wistar albino rats divided into six groups. First group received normal saline orally, the second group received turmeric extract (100 mg·kg(-1)) orally for 30 days, the third group received turmeric extract (200 mg·kg(-1)) orally for 30 days, the fourth group received a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, the fifth group received turmeric extract (100 mg·kg(-1)) orally for 30 days and a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, and the sixth group received turmeric extract (200 mg·kg(-1)) orally for 30 days and single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30. Four days after methotrexate injection, animals were anesthetized, blood samples were taken to determine total antioxidant status (TAS) and jejunum samples were taken for glutathione peroxidase (GPx), superoxidase dismutase (SOD), catalase (CAT), aldehyde malondialdehyde (MDA), and histopathological assessment. RESULTS: Microscopic evaluation from intestinal tissues of the MTX treated group, showed severe villus shortening and blunting, inflammatory cell infiltration and hemorrhage in lamina propria, along with epithlial cell necrosis. Levels of SOD, GSH-Px and CAT decreased in the MTX received group, but increased significantly (P < 0.05) in the turmeric + MTX groups. MTX increased lipid peroxidation, however, turmeric decreased peroxidation significantly (P < 0.05). CONCLUSION: These results suggest that turmeric extract may protect the small intestine of rats from methotrexate-induced damage. Turmeric effects could result from its antioxidant properties.

Evaluation of the Effect of Two Systemic Doses of HESA-A on Prevention of Induced Tongue Neoplasm in Rats.

Background and aims. The aim of the present study was to compare the inhibitory effects of two systemic doses of HESA-A on prevention of 4-NQO-induced tongue neoplasms in rats. This study evaluated weight and histopathological changes. Materials and methods. Forty-eight male Sprague Dawley rats were divided into four groups of A, B, C and D of each 12 rats. The rats in groups B to D received 30 ppm of 4-Nitroquinoline-1-oxide (4-NQO) in drinking water for 12 weeks.  When feeding with 4-NQO was initiated, the rats in groups B and C received HESA-A at doses of 250 and 500 mg/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. Results. The mean body weights of rats in groups B, C and D were significantly lower than that in group A (P < 0.05). There were no significant differences in weight changes between groups B, C and D. In the present study, after 12 weeks of treatment, Tongue specimens in groups B and C did not exhibit severe dysplastic changes; however, concurrent hyperplasia, without atypia and mild-to-moderate dysplastic changes were detected. These changes were significantly less than those in group D, with significant differences between group D and groups A, B and C (P<0.001, P<0.01 and P<0.05, respectively). Conclusion. HESA-A has dose-dependent inhibitory effects on the development of neoplasms of the tongue.

Protective Effects of Green Tea Extract against Hepatic Tissue Injury in Streptozotocin-Induced Diabetic Rats.

Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75 mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P < 0.05) and significantly decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P < 0.05) and were significantly increased in Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats.

Osseous reaction to implantation of two endodontic cements: Mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM)

Aim: The aim of the present in vivo study was to determine bone tissue reaction to calcium enriched mixture (CEM) and mineral trioxide aggregate (MTA) using a rat femur model.Study Design: Sixty-three rats were selected and randomly divided into three groups of 21 each [experimental groups (n=15), control (n=6)]. Implantation cavities were prepared in each femoral bone and randomly filled with the biomaterials only in the experimental groups. The animals in three groups were sacrificed 1, 4, and 8 weeks postoperatively. Histologic evaluations comprising inflammation severity and new bone formation were blindly made on H&E-stained decalcified 6-µm sections. Results: At 1, 4, and 8 weeks after implantation number of inflammatory cells had decreased in the CEM, MTA and control groups, respectively, with no statistically significant differences. Conversely, new bone formation had increased in all the experimental and control groups, without statistically significant differences.Conclusion: The results suggest that biocompatibility of MTA, as gold standard, and CEM cement as a new endodontic biomaterial are comparable (AU)

Osseous reaction to implantation of two endodontic cements: Mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM).

AIM: The aim of the present in vivo study was to determine bone tissue reaction to calcium enriched mixture (CEM) and mineral trioxide aggregate (MTA) using a rat femur model. STUDY DESIGN: Sixty-three rats were selected and randomly divided into three groups of 21 each [experimental groups (n=15), control (n=6)]. Implantation cavities were prepared in each femoral bone and randomly filled with the biomaterials only in the experimental groups. The animals in three groups were sacrificed 1, 4, and 8 weeks postoperatively. Histologic evaluations comprising inflammation severity and new bone formation were blindly made on H&E-stained decalcified 6-µm sections. RESULTS: At 1, 4, and 8 weeks after implantation number of inflammatory cells had decreased in the CEM, MTA and control groups, respectively, with no statistically significant differences. Conversely, new bone formation had increased in all the experimental and control groups, without statistically significant differences. CONCLUSION: The results suggest that biocompatibility of MTA, as gold standard, and CEM cement as a new endodontic biomaterial are comparable.

Effect of turmeric and carrot seed extracts on serum liver biomarkers and hepatic lipid peroxidation, antioxidant enzymes and total antioxidant status in rats.

INTRODUCTION: Pathogenic role of free radicals are well known in various metabolic diseases. They originate from internal and external sources of body. Essential roles of antioxidant defense system for cellular redox regulation and free radical scavenging activity were described in this study. Many in vitro investigations have shown that turmeric (TE) and carrot seed extract (CSE) exhibits to possess antioxidant activities. In this study, we evaluated the antioxidant potentials of ethanolic TE and CSE based on in vivo experiment in the rats. METHODS: ANIMALS WERE ASSIGNED TO SIX GROUPS: the 1st and 2nd groups were control groups and 2nd group received 0.2 ml dimethyl sulphoxide as vehicle treated group; other four experimental groups received different doses of TE (100, 200 mg/kg b.w.) and CSE (200, 400 mg/kg b.w.) by gavages, respectively for a period of one month. The indicators of oxidative stress, lipids peroxidation, markers of hepatocyte injury and biliary function markers were measured. RESULTS: The levels of superoxide dismutase, catalase, and glutathione peroxidase were significantly stimulated in the hepatic tissue of treatment groups. The malondialdehyde contents of liver tissue were significantly reduced in the groups fed with TE and CSE. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, in treated groups were found to be significantly decreased, whereas albumin and total protein increased as compared to the control groups (P<0.05). CONCLUSION: this study showed that the regular intake of TE and CSE through the diet can improve antioxidant status and inhibit peroxidation activity in the liver tissue so that using these extracts may protect tissue oxidative stress.

Microscopic comparison of topical use of Mitomycin C and Fluorouracil on cold knife myringotomy.

UNLABELLED: Objective/hypothesis A comparison of the histopathological effect of topical use of Mitomycin C and 5-Fluorouracil in preventing myringotomy closure in rats. STUDY DESIGN: clinical trial. Methods and materials The study was performed on 43 rats that were divided into three groups. Study groups (A and B) and control group (C) after bilateral cold-knife myringotomy, we applied Mitomycin C (MMC) 4mg/ml to group A, 5-Fluouracil (5FU) 50mg/ml to group B, and normal saline to group C. An examination of all ears of rats was carried out by otoscope on days 0, 1, 3, 5, 7, and then every five days up to 70 days. Each day's closed myringotomies of all groups were examined. Results The mean of post myringotomy opening time was 37, 16, and 12 days respectively in MMC, 5FU, and saline. Patency duration of MMC group was significantly long (p<0.0001), but in histopatholgical examinations, sclerosis of tympanic membrane in MMC group showed the highest patency duration (p<0.0001). Conclusion Mitomycin C significantly prolonged the duration of myringotomy patency time - longer than 5-Fluouracil and saline but with the adverse effects of tympanic membrane fibrosis.