In this study, the effect of mirtazapine on rat kidneys versus ischemia-reperfusion (IR) damage was biochemically and histopathologically investigated. The results have shown that malondialdehyde (MDA) level of healthy rat group is 15.2 mol/g protein. The level of this substance was measured as 26.7 mol/g in only ischemia group. The MDA levels of IR and mirtazapine + renal ischemia-reperfusion (MRIR) groups were 39 ± 17.6 mol/g protein. While myeloperoxidase activity of healthy rat group was 20.2 u/g, the activities of only ischemia, IR, and MRIR groups were 28, 36.3, and 21 u/g, respectively. The glutathione levels were measured as 17.7, 12.8, 7.5, and 16.2 nmol/g in healthy, only ischemia, IR, and MRIR groups, respectively. Finally, glutathione S-transferase activities of healthy, only ischemia, IR, and MRIR groups were determined as 20, 13.8, 7.1, and 18.3 u/g, respectively. Histopathologically, while hemorrhage in interstitial area was observed in only ischemia group, significant tubular epithelial swelling, necrosis, and cast accumulation were seen in IR group. In MRIR group, only mild tubular epithelial swelling and mild hyaline cast accumulation were observed in kidney tissue. Consequently, it can be said that mirtazapine has a protective effect on IR-induced kidney damage.

SummaryBackgroundOxidative liver injury occurring with methotrexate restricts its use in the desired dose. Therefore, whether or not thiamine and thiamine pyrophosphate, whose antioxidant activity is known, have protective effects on oxidative liver injury generated with methotrexate was comparatively researched in rats using biochemical and histopathological approaches.Material/MethodsThiamine pyrophosphate+methotrexate, thiamine+methotrexate, and methotrexate were injected intraperitoneally in rats for 7 days. After this period, all animals’ livers were excised, killing them with high-dose anesthesia, and histopathologic and biochemical investigations were made.ResultBiochemical results demonstrated a significant elevation in level of oxidant parameters such as MDA and MPO, and a reduction in antioxidant parameters such as GSH and SOD in the liver tissue of the methotrexate group. Also, the quantity of 8-OHdG/dG, a DNA injury product, was higher in the methotrexate group with high oxidant levels and low antioxidant levels, and the quantity of 8-OHdG/dG was in the thiamine pyrophosphate group with low oxidant levels and high antioxidant levels. In the thiamine and control groups, the 8-OHdG/dG rate was 1.48±0.35 pmol/L (P>0.05) and 0.55±0.1 pmol/L (P<0.0001). Thiamine pyrophosphate significantly decreased blood AST, ALT and LDH, but methotrexate and thiamine did not decrease the blood levels of AST, ALT and LDH. Histopathologically, although centrilobular necrosis, apoptotic bodies and inflammation were monitored in the methotrexate group, the findings in the thiamine pyrophosphate group were almost the same as in the control group.ConclusionsThiamine pyrophosphate was found to be effective in methotrexate hepatotoxicity, but thiamine was ineffective.

In this study, the biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue were investigated. Animals were divided into four groups of six rat each, ovarian ischemia-reperfusion (IR), 25 mg/kg thiamine + ovarian ischemia-reperfusion (TIR), 25 mg/kg thiamine pyrophosphate + ovarian ischemia-reperfusion (TPIR) and Sham group (SG). The results of the biochemical experiments have shown that the rat ovarian tissue with thiamine treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the IR group; while in the group with thiamine pyrophosphate treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the SG. Ovarian tissue of rats in the IR group were congested and dilated vessels, edema, hemorrhage, necrotic and apoptotic cells. In this group, the migration and the adhesion of the polymorphonuclear leucocytes to the endothelium were observed. Both ovaries in TPIR group, there was no difference according to the SG. Histopathology of ovarian tissues in the TIR group was almost the same with the IR group. Our results indicate that thiamine pyrophosphate significantly prevents the ischemia-reperfusion induced oxidative damage in ovarian tissue, whereas thiamine has no effect. In conclusion, we have found that thiamine pyrophosphate prevents oxidative damage due to ischemia-reperfusion injury, whereas thiamine does not have this effect. Furthermore, we have confirmed that the results of our biochemical analyses are in concordance with the histopathological findings.

Objective: Angiogenesis plays a key role in tumor growth and metastasis. Determination of microvessel density is the most common technique used to evaluate the amount of the intratumoral angiogenesis in breast cancer. We have aimed to investigate the relationship with tumor angiogenesis and prognostic parameters in breast invasive ductal carcinomas. Material and Method:In this study, a total of 100 invasive ductal carcinoma patients, who were diagnosed at the Department of Pathology, Ataturk university Faculty of medicine between the years 2003-2008, were re-evaluated. Patient characteristics and clinicopathological findings were obtained from archival records. In the present study, microvessel density was determined by immunohistochemical staining by using anti-CD34 monoclonal antibody in the paraffin blocks. First, the most vascular area was selected in the tumor under a low magnification (40x) by a light microscope and then microvessels were counted under a higher magnification (200x). Patients were classified as low and high microvessel density depending on their microvessel counts. Chi-square test and multivariate linear regression analysis were used for statistical analysis (p≤0.05). Results:We have determined that microvessel density increases as tumor size increases (p=0.001). microvessel density was higher in patients with at least 10 lymph node metastases compared to those with no metastasis (p=0.05). However, there was no statistically significant difference between microvessel density and other prognostic factors such as histological grade, nuclear grade, patient age, vascular invasion, estrogen, progesterone receptor status, HEr2/neu expression. Conclusion:In our study, we have found that microvessel density is associated with tumor size and lymph node metastasis in patients with invasive ductal carcinoma.

In the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.