Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis.

OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis

Abstract Objective: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. Methodology: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1β (IL-1β), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. Results: Although the IL-1β, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). Conclusion: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Cucurbitacin E shows synergistic effect with sorafenib by inducing apoptosis in hepatocellular carcinoma cells and regulates Jak/Stat3, ERK/MAPK, PI3K/Akt/mTOR signaling pathways.

OBJECTIVE: Cucurbitacin E (CuE), a natural compound found in medicinal plants such as Ecballium Elaterium, has demonstrated antiproliferative and apoptotic effects in various cancer cell types due to its tetracyclic triterpenoid structure. Sorafenib, a multi-tyrosine kinase inhibitor, is commonly used in hepatocellular carcinoma (HCC) treatment. This study aimed to investigate the anticancer effect of CuE alone and in combination with sorafenib on HepG2 cells. METHODS: CuE was extracted from Ecballium Elaterium fruit juice and quantitatively evaluated using HPLC. The effect of sorafenib and CuE on cell growth inhibition was determined using the MTT test. Cell cycle progression and apoptosis were assessed using flow cytometry. Mitochondrial damage was evaluated with ΔΨm, and DNA damage was assessed using the comet assay. The expression of Jak2/Stat3, PI3K/Akt/mTOR, MAPK, and Bcl-2 family-related genes and proteins were analyzed using western blot and qRT-PCR, respectively. RESULTS: Both CuE (0.1-5 µM) and sorafenib (0.5-10 µM) exhibited dose- and time-dependent antiproliferative and cytotoxic effects against the HepG2 cell line. Both compounds induced apoptosis in HepG2 cells and halted the cell cycle in the G2/M phase while causing mitochondrial and DNA damage. Both compounds down-regulated Jak2/Stat3, PI3K/Akt/mTOR, MAPK signaling pathway proteins, and Bcl-xL levels, while up-regulated Caspase-9 and Bax protein levels. CONCLUSION: Based on the results of this study, it can be concluded that CuE alone or in combination with sorafenib has the potential to be an effective therapeutic option for the treatment of HCC by inducing apoptosis and regulating multiple signaling pathways.

Tissue Heavy Metals in Liver Diseases.

BACKGROUND: Our objective was to determine the levels of heavy metals, oxidants, and antioxidants in liver tissue of patients with chronic liver disease (CLD) compared with healthy living liver donors (LLDs). METHODS: We obtained liver specimens from patients undergoing liver transplant for CLD. Samples were also obtained from LLDs. Biochemical analyses were performed on all samples, and the levels of liver tissue, heavy metal, and oxidant-antioxidants biomarker levels in patients with CLD were compared with those measured in LLDs. RESULTS: One hundred and eighteen individuals were included for analyses. Fifty-nine were patients with CLD, and 59 were LLDs. The median levels of liver tissue of superoxide dismutase (P = .009), glutathione peroxidase (P = .042), total oxidant status (P = .006), oxidative stress index (P < .001), and copper (P = .035) were prominently more elevated in CLD than LLDs. On the other hand, the median levels of liver tissue of cadmium (P < .001), selenium (P = .042), and zinc (P < .001) levels were more elevated in the LLDs than patients with CLD. The 2 groups were similar in terms of total antioxidant status, manganese, arsenic, and lead levels. CONCLUSIONS: Superoxide accumulation in the liver was higher in patients with CLD. Concerning heavy metals, only the median tissue copper was elevated in patients with CLD with higher Cu/Zn ratio. Cadmium, selenium, and zinc were significantly higher in the healthy LLDs.

Effects of ciprofloxacin and quercetin on fetal brain development: a biochemical and histopathological study.

PURPOSE: Teratogens cause birth defects and malformations while human development is being completed. In pregnancy, urinary tract infection (UTI) is a common health problem caused by bacteria. The fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin can treat various types of bacterial infections successfully. The aim of this study is to determine whether the use of ciprofloxacin during pregnancy causes oxidative stress on brain tissues of the fetus, and whether quercetin contributes to prevent this damage if stress has already occurred. MATERIALS AND METHODS: In our study, 22 young female Wistar albino rats weighing 250 g were used. Rats were mated overnight in separate plastic cages. Female rats were regarded as pregnant when a vaginal plug was observed, and these were divided into four groups of control, ciprofloxacin, quercetin, and cipro + quercetin. Two daily i.p. 20 mg/kg doses of ciprofloxacin were administered to ciprofloxacin group between 7 and 17 d of pregnancy. Throughout the study, daily (20 d) 20 mg/kg quercetin was dissolved in corn oil and administered to the quercetin group by oral gavage. Rats were fed ad libitum throughout the study. Fetuses were taken by C-section on the 20th day of pregnancy. Thereafter, the brain tissues were subjected to histological assessments and biochemical analyzes. RESULTS: The experimental groups were compared with the control group; ciprofloxacin affected fetal development, especially caused damage to neurons in brain tissue and cause hemorrhagic defects. And also, it was determined that many parameters were affected such as antioxidant parameters, enzyme levels and levels of malondialdehyde (MDA) (a marker of lipid peroxidation). Quercetin is a member of flavonoid with strong antioxidant properties, and our results indicate that the use of ciprofloxacin in pregnancy can result damage to fetal brain tissue. CONCLUSIONS: Unlike these results when some parameters are evaluated it is understood that this harmful effects suppressed by quercetin.

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.

BACKGROUND: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Study of the neuroprotective effect of ginseng on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in experimental diffuse head trauma.

BACKGROUND: The purpose of our study was to investigate the effect of ginseng on antioxidant enzyme levels in brain damage following experimental diffuse head trauma in rats. The neuroprotective effect of ginseng was also studied. METHODS: In this study, rats were divided into four groups, and the rats in group 1 received no intervention. In group 2, the rats were administered 50 mg/kg ginseng, injected intraperitoneally at 1, 24 and 48 h, and the effect of ginseng on normal tissues was studied. No drugs were administered to the rats in group 3 who had previously experienced diffuse head trauma using Feeney's falling weight method. In group 4, rats underwent Feeney's falling weight method, leading to diffuse head trauma, and they were given 50 mg/kg ginseng intraperitoneally 1, 24 and 48 h after head trauma. Rats were killed 72 h after head trauma and their brain tissues extracted for histopathological and biochemical studies. RESULTS: Histopathological study of brain cross sections in the trauma group demonstrated neurons in the trauma region and surrounding area, which generally had a dark-colored eosinophilic cytoplasm and a pyknotic nucleus, while the nuclei of neurons were located peripherally. However, brain cross sections in group 4 from rats given ginseng after head trauma showed fewer neurons with eosinophilic cytoplasm, pyknotic and peripheral nuclei in the trauma region and surrounding area. No statistically significant difference in the tissue SOD level was observed; however, the GSH Px level in group 4 was significantly reduced compared to that in group 3. CONCLUSIONS: After affecting the GSH Px level and reducing histopathological scores, ginseng was found to display antioxidant and neuroprotective activity.

Ameliorative effects of resveratrol on acute ovarian toxicity induced by total body irradiation in young adult rats.

OBJECTIVE: The purpose of this study was to investigate the ovarian protective effects of resveratrol in rats exposed to total body irradiation. DESIGN: Experimental study. SETTINGS: University hospital. PARTICIPANTS AND INTERVENTIONS: Thirty female rats were randomized into four groups: (1) control group (n = 7); (2) low-dose (10 mg/kg) resveratrol group (n = 8); (3) high-dose (100 mg/kg) resveratrol group (n =7); and (4) sham irradiation group (n = 8). The drugs were administered intraperitoneally as single doses, and the rats were exposed to total body radiation 24 h after the treatment. The animals were sacrificed the following day, and their ovaries were excised for histopathological and biochemical analysis. MAIN OUTCOME MEASURES: The ovarian follicle counts were calculated, and irradiation-dependent ovarian damage and tissue levels of antioxidant enzymes were evaluated. RESULTS: Group 2 and Group 3 showed significantly higher numbers of total follicle counts compared with Group 1 (P < 0.01). The low-dose resveratrol treatment was associated with significantly higher numbers of primary follicles than the high-dose group. The tissue activities of glutathione peroxidase (GsH-Px) and catalase (CAT) were significantly elevated in the resveratrol-treated animals. Evaluation of ovarian histology revealed no remarkable changes in fibrosis and leucocyte infiltration among the resveratrol-treated and control rats; however, vascularity was significantly reduced in the high-dose group (P = 0.014). CONCLUSION: Resveratrol attenuated irradiation-dependent ovarian damage, suggesting that this natural antioxidant is effective in reducing the follicle loss induced by ionizing radiation.

Beneficial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study.

The effects of montelukast against methotrexate-induced liver damage were investigated. 35 Wistar albino female rats were divided into 5 groups as follows: group I: control; group II: montelukast (ML); group III: methotrexate (Mtx); group IV: montelukast treatment after methotrexate application (Mtx + ML); group V: montelukast treatment before methotrexate application (ML + Mtx). At the end of the experiment, the liver tissues of rats were removed. Malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione levels were determined from liver tissues. In addition, the liver tissues were examined histologically. MDA and MPO levels of Mtx group were significantly increased when compared to control group. In Mtx + ML group, these parameters were decreased as compared to Mtx group. Mtx injection exhibited major histological alterations such as eosinophilic staining and swelling of hepatocytes. The glycogen storage in hepatocytes was observed as decreased by periodic acid schiff staining in Mtx group as compared to controls. ML treatment did not completely ameliorate the lesions and milder degenerative alterations as loss of the glycogen content was still present. It was showed that montelukast treatment after methotrexate application could reduce methotrexate-induced experimental liver damage.

Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury.

Spinal cord injury (SCI) results in loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into cells has been postulated to be a key early event in the pathogenesis of secondary traumatic and ischemic central nervous system injury. Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection. The purpose of the present study was to compare the neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and riluzole--after SCI. Ninety rats were randomly and blindly divided into five groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1 mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80 mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for determination of spinal cord water content and malondialdehyde (MDA) levels. Motor function scores of six rats from each group were evaluated weekly for six weeks. Then the rats were killed for histopathological assessment. Although all the treatment groups revealed significantly lower MDA levels and spinal cord edema than the trauma group (p<0.05), the riluzole and mexiletine treatment groups were better than the phenytoin treatment group. In the chronic stage, riluzole and mexiletine treatment achieved better results for neurobehavioral and histopathological recovery than phenytoin treatment. In conclusion, all the tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and mexiletine were superior to phenytoin.

Evaluation of the neuroprotective effects of citicoline after experimental spinal cord injury: improved behavioral and neuroanatomical recovery.

Spinal cord injury (SCI) caused by trauma mainly occurs in two mechanisms as primary and secondary injury. Secondary injury following the primary impact includes various pathophysiological and biochemical events. Methylprednisolone is the only pharmacological agent having clinically proven beneficial effects on SCI. Citicoline has been shown to have clinical and experimental beneficial effects on brain ischemia. This study aims to investigate the neuroprotective effect of citicoline in an experimental SCI model in rats. Sixty adult Wistar albino rats were randomized into five groups. SCI was performed by the weight-drop model. Group 1 underwent laminectomy alone. The Group 2 underwent laminectomy followed by SCI and received no medication. Group3, Group 4 and Group 5 underwent laminectomy followed by SCI and received medication. Group 3 and Group 5 received citicoline and Group 4 and Group 5 received methylprednisolone. The rats were divided into two subgroups for biochemical analysis (sacrificed at 24 h after surgery) and neurobehavioral and histopathological evaluation (sacrificed at 6 weeks after surgery). Malondialdehyde levels, nitric oxide levels and trauma size ratios were lower and reduced glutathione levels were higher in Group 3, Group 4 and Group 5 as compared to Group 2. Posttraumatic neurological recovery after surgery was significantly better in Group 3, Group 4 and Group 5 compared to Group 2. In conclusion, this study demonstrates that citicoline is as effective as methylprednisolone. The efficacy of citicoline combined with methylprednisolone is not superior to either citicoline or methylprednisolone alone.

Resveratrol, a red wine constituent polyphenol, protects from ischemia-reperfusion damage of the ovaries.

OBJECTIVE: The aim of this study is to investigate the effects of resveratrol on histopathological changes, antioxidant status and lipid peroxidation, in torsion-detorsion injury in rat ovaries. METHOD: To determine whether ischemia followed by reperfusion can induce ovarian oxidative damage, we created a model of adnexal ischemia-reperfusion by using rats. Ischemia was induced by unilateral occlusion of the tubo-ovarian vessels for 3 h. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 3 h. Thirty-two adult female albino rats were divided equally into 4 groups: sham operation, torsion, saline/detorsion and resveratrol/detorsion. Rats in the torsion group were killed after 360 degrees clockwise adnexal torsion for 3 h. Resveratrol was injected intraperitoneally 30 min before detorsion in the resveratrol/detorsion group, and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion in both of these groups, the rats were killed and adnexa were removed. The tissue levels of malondialdehyde, reduced glutathione and xanthine oxidase activity were measured. RESULTS: Malondialdehyde and xanthine oxidase levels in the saline/detorsion group were increased significantly when compared to the torsion and sham operation groups (p < 0.001). Malondialdehyde levels in the resveratrol group were lower than in the saline/detorsion group, and differences between the two groups were statistically significant (p < 0.001). Xanthine oxidase levels in the resveratrol group were lower than in the saline/detorsion and torsion groups, and differences between these groups were statistically significant (p < 0.001). Reduced glutathione levels in the saline/detorsion group were decreased significantly when compared to the torsion and sham operation groups. Reduced glutathione levels in the resveratrol group were significantly higher than in the saline/detorsion group (p < 0.006). Histological examination showed a significant improvement in ovarian morphology in the resveratrol-treated rats compared with the ischemia and ischemia-reperfusion groups. CONCLUSION: Our results demonstrated that intraperitoneal resveratrol administration reduced the lipid peroxidation products of ischemic rats and ovarian damage was reduced as indicated by histological examination.