Onur Erdem

Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress.

Mucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had a protective effect on methotrexate-induced small intestine damage. Twenty-eight albino rats were randomized into four groups. To the first group, methotrexate was applied as a single dose (20mg/kg) intraperitoneally. To the second group, proanthocyanidin (100mg/kg) was given orally every day by gavage in addition to methotrexate application until the rats were killed. To the third group, only proanthocyanidin was administered. The fourth group was the control. All animals were sacrificed 4 days after the intraperitoneal injection of methotrexate for histopathological examination and the assay for tissue malondialdehyde, superoxide dismutase and glutathione peroxidase levels. Methotrexate caused jejunal injury and increased malondialdehyde levels. Administration of proanthocyanidin decreased the jejunal damage and malondialdehyde level, which were caused by methotrexate treatment and increased superoxide dismutase and glutathione peroxidase levels. These results suggest that proanthocyanidin may protect the small intestine of rats from methotrexate-induced damage. The effects of proanthocyanidin could result from its antioxidant properties.

Cytogenetic analysis of peripheral blood lymphocytes of hospital staff occupationally exposed to low doses of ionizing radiation

Ionizing radiation is known to induce mutations and cell transformations, predominantly by causing single-strand and double-strand DNA breakage, thereby leading to chromosome instability and carcinogenesis. The aim of this study was to evaluate genotoxic effects in hospital staff exposed to low-dose ionizing radiation in comparison with a selected control group, by using the cytokinesis-blocked micronucleus (CBMN) and sister chromatid exchange (SCE) tests in peripheral blood lymphocytes. The study included 40 exposed radiology staff and 30 control subjects. The frequency of micronuclei (MN) was significantly increased in radiation-exposed groups compared with control persons (p < 0.05). The frequency of SCE did not show any significant difference in the exposed individuals in comparison to the controls. Our results showed that low-level chronic occupational exposure to ionizing radiation causes an increase of MN frequency in chromosomes, even though the absorbed doses were below the permissible limits. Our studies indicate that the CBMN assay is considered to be sensitive test in contrast to SCE analysis to evaluate chromosomal damage induced by ionizing radiation.

In vivo evaluation of the effects of hydraulic calcium silicate dental cements on plasma and liver aluminium levels in rats

Our aim was to test whether the presence of three hydraulic calcium silicate dental cements--MTA Angelus, MTA Fillapex, and Theracal LC--in the dental extraction socket of an in vivo model, would affect the levels of aluminium (Al) in the plasma and liver. Following anesthesia, the right upper incisor of each male Wistar albino rat was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex, or Theracal LC were inserted into the depth of the extraction socket and gingival tissue was sutured. The rats were killed 7, 30, or 60 d after the operation. Blood and liver samples were obtained from the rats before they were killed, and the levels of Al were measured by atomic absorption spectrometry. Plasma Al levels were higher in the rats in which the mineral trioxide aggregate (MTA) cements were implanted, especially MTA Angelus and MTA Fillapex, compared with control rats. In liver samples, however, the differences in Al level were not statistically significant. Our results show that Al might have been released into the circulation from the three dental cements tested, especially MTA Angelus and MTA Fillapex. Further research should be carried out on the possible biological effects of Al liberated from dental cements.

Induced antioxidant activity in hospital staff occupationally exposed to ionizing radiation

Abstract Purpose: Occupational exposure to low levels of ionizing radiation (IR) in radiology department staff may affect their antioxidant status. The aim of this study was to evaluate the oxidative stress parameters in radiology staff that are occupationally exposed to IR in a hospital setting. Materials and methods: The study population included 40 exposed radiology staff and 30 control subjects. The radiation doses of exposed staff ranged between 0.10 and 3.8 milligray (mGy) per month. The subjects’ antioxidant status was determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. Results: Our results showed that the activities of erythrocyte CuZn-SOD and Se-GPx enzymes observed for the radiation exposed group were significantly higher than in the controls. The activity of CAT enzyme and MDA levels were significantly lower in the exposed group than in the controls. Moreover, we investigated the influence of confounding factors on antioxidant enzymes or lipid peroxidation (LP), but we could not find any associations between them. Conclusions: Our study indicates the presence of stimulant effect of chronic low-dose radiation in exposed individuals, resulting in enhanced resistance to oxidative stress.

Association of GPX1 polymorphism, GPX activity and prostate cancer risk

Prostate cancer is the second most common cancer in men worldwide. Although the aetiology of this disease remains largely unclear, several lines of evidence suggest that oxidative stress plays a role in prostate carcinogenesis. The antioxidant enzyme glutathione peroxidase 1 (GPX1) is part of the enzymatic antioxidant defence, preventing oxidative damage to DNA, proteins and lipids by detoxifying hydrogen and lipid peroxides that may contribute to prostate cancer development. Some studies indicate an association between GPX1 Pro198Leu polymorphism and an increased risk of cancer. The purpose of the present study was to determine the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Turkish population. The GPX1 Pro198Leu genotype was determined in 33 prostate cancer patients and 91 control individuals. As evident from our results, there was no difference between genotype and/or allele frequencies in prostate cancer patients and controls. No significant difference was found in GPX1 genotype or allele frequency between aggressive and non-aggressive prostate cancer patients. It can be suggested with these findings that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism, but it needs further studies.

Involvement of galectin-3 in cadmium-induced cardiac toxicity.

OBJECTIVE Accumulation of the wide spread environmental toxin cadmium (Cd) in tissues results in toxicity. Heart is one of the most effected tissues. Cd exposure induces inflammation in effected tissues. The present study was focused to evaluate roles of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in Cd toxicity and their relationships with galectin-3 levels. METHODS In this experimental study, male Wistar rats were divided randomly to control and experimental groups. Experimental group was exposed to Cd at the dose of 15 ppm for 8 weeks (n=10/group). Inflammatory status in hearts was evaluated with measurement of tissue TNF-α and IL-6 levels. Histopathological examination of heart was carried out by light microscopy. Heart tissue caspase-3 level was used to identify apoptosis. Tissue galectin-3 level was evaluated by ELISA. Statistical difference between groups was evaluated by unpaired Student t-test, correlation was analyzed by Pearsons test. RESULTS Heart sizes were increased after Cd toxicity. A significant increase in galectin-3 tissue levels was seen after Cd toxicity, this was accompanied with a significant increase in the TNF-α (control: 402±39, Cd: 793±26 pg/g tissue, p<0.001) and IL-6 (control: 150±78, Cd: 325±65 pg/g tissue, p<0.001) levels. Histopathological examination under light microscope suggested a combination of ongoing necrosis and apoptosis. Increased caspase-3 levels were measured after Cd toxicity (control: 12±2, Cd: 18±3 pmol/µg/min, p<0.001). CONCLUSION Chronic Cd administration induces inflammation and apoptosis in rat hearts. Cadmium causes increased galectin-3 production from heart tissue. The formation of TNF-α due to Cd exposure may likely trigger this mechanism.

Role of midkine in cadmium-induced liver, heart and kidney damage

Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p < 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p < 0.05, p < 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.

The effect of melatonin on procarbazine induced testicular toxicity on rats

Abstract Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects.

Association between Gene Polymorphism of Manganese Superoxide Dismutase and Prostate Cancer Risk

Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species‐induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala‐9Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early‐onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala‐9Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early‐onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk.

Brain aluminium accumulation and oxidative stress in the presence of calcium silicate dental cements

Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.