High dose zoledronic acid increases ischemia-reperfusion damage of the liver.

OBJECTIVE: Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, has been reported to exhibit a protective effect against cancers and prevent bone fractures. It also induces apoptosis by increasing proinflammatory cytokines and oxidative stress. Oxidative stress increases significantly during ischemia-reperfusion (IR) injury. The liver is highly sensitive to IR injury. In this study, we aim to investigate whether high-dose ZA treatment affects the liver during IR. MATERIALS AND METHODS: We used twenty-one Sprague-Dawley male rats in our study, and they were subdivided randomly into three groups, each containing seven rats. A single dose of 100 µg/kg ZA was administered via the intraperitoneal route in the ZA group. Forty-eight hours after the ZA administration, infrarenal abdominal aortic cross ligation was performed on the ZA and IR groups. After 2 hours of ischemia, 2 hours of reperfusion was applied. RESULTS: The malondialdehyde (MDA) level of the control group was significantly lower than the IR (p = 0.006) and ZA (p<0.001) groups. However, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values of the control group were significantly higher than the values of the IR group (p<0.05, p<0.001, and p<0.05) and ZA group (p = 0.002, p<0.001, and p<0.001). Caspase-3 activity was significantly higher in the IR group as compared to the control group (p<0.001). The caspase-3 activity in the ZA group, on the other hand, was higher than both the control (p<0.001) and IR groups (p<0.001). CONCLUSIONS: High-dose ZA may exacerbate liver injury during IR by increasing reactive oxygen species production and apoptosis.

The role of the adhesion molecule Nectin-4 in the pathogenesis of endometriosis.

OBJECTIVE: Nectins are immunoglobulin-like adhesion molecules, and they play important role in cell proliferation and tumor metastasis. The objective in this study was to compare the expression of Nectin-4 in normal endometrium and in ectopic endometriotic tissues. MATERIALS AND METHODS: Nectin-4 expression was investigated in ovarian endometriosis (n = 20), peritoneal endometriosis (n = 20), endometrium of endometriosis (n = 20), and in a control group (having no endometriosis) (n = 20) by immunohistochemical method. RESULTS: Nectin-4 expression, when compared with control group, was higher in endometriotic lesions of patients having ovarian endometriosis and peritoneal endometriosis (p = 0.003 and p = 0.009, respectively). This difference was significant in the endometrium of patients having endometriosis (p = 0.011). CONCLUSION: The authors believe that Nectin-4 molecule may contribute to the pathogenesis of endometriosis. For this reason, the use of medicines developed against this molecule in the treatment of endometriosis may be useful.

Protective effects of thymoquinone and alpha-tocopherol on the sciatic nerve and femoral muscle due to lower limb ischemia-reperfusion injury.

OBJECTIVE: Thymoquinone (TQ) is an antioxidant and anti-apoptotic substance found in the Nigella sativa plant. Alpha-tocopherol (α-TP) is a potent antioxidant. We aimed to determine whether or not TQ and TP have a protective effect against lower limb ischemia-reperfusion (IR) injury of muscle and the sciatic nerve. MATERIALS AND METHODS: A single dose of TQ 25 mg/kg was given intraperitoneally to the TQ group, a single dose of α-TP 200 mg/kg was given intraperitoneally to the α-TP group. IR was performed for 45 minutes after the drugs' applications. RESULTS: While serum levels of malondialdehyde (MDA) and interleukin-6 (IL-6) of the IR group were significantly higher than those of the TQ plus α-TP, TQ and α-TP groups (p<0.001, p<0.001, p=0.008, respectively) and IL-6 (all p<0.001), the reduced glutathione (GSH) level of the IR group was lower than that of the other three groups. While neuronal nitric oxide synthase activity of nerve tissues of the IR group was significantly lower than that of the TQ plus α-TP group, the muscle tissue caspase-3 activity was higher than that of the TQ plus α-TP group. CONCLUSIONS: Administration of TQ plus α-TP may strongly protect muscle and nerve tissues against IR injury via their synergistic effects.

Topiramate has protective effect on renal injury.

BACKGROUND: Topiramate (TPM) decreases tumor necrosis factor-alpha (TNF-α) and oxidative stress. We investigated protective effects of TPM on cell damage in kidney tissue during ischemia-reperfusion (I/R) damage. METHODS: A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus TPM (I/R+TPM). Laparotomy without I/R injury was performed in control group. After laparotomy, cross ligation of infrarenal abdominal aorta was applied for two hours in I/R groups which was followed by two hours of reperfusion. TPM (100 mg/kg/day) was orally administrated to animals in the I/R+TPM group for seven consecutive days before I/R. RESULTS: The I/R group's TNF-α and interleukin-1 beta (IL-1ß) levels were significantly higher (1184.2 ± 129.1 pg/mg protein; 413.1 ± 28.8 pg/mg protein, respectively) than those of the control (907.8 ± 113.0 pg/mg protein, p = 0.002; 374.7 ± 23.7 pg/mg protein, p = 0.010, respectively) and I/R+TPM groups (999.5 ± 115.2 pg/mg protein, p < 0.001; 377.9 ± 30.9 pg/mg protein, p = 0.007, respectively). CONCLUSION: TPM may partially prevent renal damage in rats. The opening of new horizons of this kind of knowledge will help understand the complex challenge in the prevention of renal I/R damage (Tab. 1, Fig. 3, Ref. 42).

The diagnostic utility of maspin in the distinction between malignant mesothelioma and pulmonary adenocarcinoma.

Immunohistochemistry is frequently employed to differentiate between malignant mesothelioma (MM) and pulmonary adenocarcinoma (AC) infiltrating the pleura, but there is uncertainty as to which antibodies are most useful. The present study investigated the presence of the serine protease, maspin, in epithelioid MMs and evaluated the diagnostic utility of maspin for the differential diagnosis between epithelioid MM and pulmonary AC with pleural involvement. The results showed more frequent maspin immunostaining among AC cases compared with MM cases. Maspin positivity was significantly higher among AC cases with respect to both the extent and intensity of staining. A significant difference also existed between the two tumour types with respect to the overall maspin score. Despite these findings, the sensitivity and specificity of maspin positivity to detect AC were only 59% and 73%, respectively, indicating that detection of maspin is of no value for the differential diagnosis of AC and MM.