Mukaddes Gulec

Antioxidant enzyme activities and oxidative stress in affective disorders

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.

Antioxidant properties of propofol and erythropoietin after closed head injury in rats.

Reactive oxygen species play a role during brain injury due to closed head trauma. Enzymatic or nonenzymatic antioxidants may protect brain tissue against oxidative damage. The present study was performed to assess the changes of endogenous indices of oxidative stress in serum from rats subjected to head trauma and whether treatment with propofol and/or erythropoietin (EPO) modifies the levels of endogenous indices of oxidative stress. For these purposes, female Wistar Albino rats were divided into five groups: non-traumatic sham group, trauma performed control, trauma with propofol (i.p.), trauma with EPO (i.p.) and trauma with propofol and EPO performed study groups. At the end of the experimental procedure, blood was taken by cardiac puncture to determine superoxide dismutase (SOD) and xanthine oxidase (XO) activities as well as malondialdehyde (MDA) and nitric oxide (NO) levels in serum. Serum MDA level of control traumatic brain injury (TBI) group was significantly higher than sham operation group (p<0.012). Serum MDA levels in propofol, EPO and propofol+EPO groups were found to be decreased in comparison with control group (p<0.039, p<0.030 and p<0.018, respectively). Serum NO level was found to be increased in TBI group, but difference was not statistically significant when compared to sham-operated group (p=0.092). Propofol, EPO and propofol+EPO administration efficiently reduced serum NO levels to reach sham-operated group (p<0.002, p<0.001 and p<0.015, respectively). These results suggested that acute administration of both propofol and EPO altered the indices of oxidative stress similarly against brain injury due to trauma.

Vitamin E protects against oxidative damage caused by formaldehyde in the liver and plasma of rats.

It is well known that formaldehyde (FA) and reactive oxygen species (ROS) are cytotoxic and potentially carcinogenic. Although the individual effects of these reactants on cells have been investigated, the cytotoxicity exerted by the coexistence of FA and ROS is poorly understood. The present study was carried out to evaluate oxidant/antioxidant status and biochemical changes occurring after chronic formaldehyde toxicity in liver tissue and plasma of rats and protective effect of vitamin E (vit E) against oxidative damage. Eighteen rats were divided into three groups: (1) control rats, (2) rats treated with FA (FAt), and (3) rats treated with FA plus vit E (FAt + vit E) groups. After the treatment, the animals were sacrificed and liver tissues were removed for biochemical investigations. As a result, FA treatment significantly increased the levels of tissue malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) and the activity of xanthine oxidase enzyme (XO). On the other hand, FA exposure led to decrease in superoxide dismutase (SOD) and catalase (CAT) activities in liver tissues compared to control. FA caused significant decreases in total protein (TP) and albumin (ALB) whereas increases in aspartate transaminase (AST), alanine aminotransferase (AST), alkaline phosphatase (ALP) and interleukine-2 (IL-2) levels in plasma. Vit E treatment abolished these changes at a level similar to the control group. It was concluded that vit E treatment might be beneficial in preventing FA-induced liver tissue damage, and therefore have potential for clinical use.

Propofol and erythropoietin antioxidant properties in rat brain injured tissue

So far, several treatment modalities have been attempted to brain protection in cases such as brain trauma, stroke or brain hemorrhage. However, a treatment method that the effect begins immediately and definitely helpful has not been discovered yet. In this study, we aimed to compare the effects of propofol and erythropoietin (Epo) on brain injury caused by oxidative stress and antioxidant properties of these agents after closed head injury (CHI) in rats. For this study, female Wistar Albino rats were divided into five groups: non-traumatic control group, trauma performed group CHI, trauma with propofol (100 mg/kg) intraperitoneally (i.p.), trauma with Epo (5000 U/kg) i.p. and trauma with propofol and Epo performed study groups. Twenty-four hours after CHI, rats were sacrificed and the brains were removed. Superoxide dismutase (SOD), catalase (CAT), xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) levels were measured in brain tissue. MDA and NO levels were decreased significantly in Groups Epo, Propofol and Epo+Propofol than Group CHI (p<0.01). XO activity was significantly lower in Group Epo than Group CHI (p<0.05). Epo and propofol decreased oxidative stress by decreasing MDA and NO level in brain tissue after CHI. However, combination of Epo and propofol has no significant beneficial advantage than Epo or propofol alone.

The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity.

This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E=cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE=cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin=GBE-treated rats; P≤0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin=GBE-treated (PB≤0.041) and cisplatin=vit E-treated (PB≤0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity. Toxicology and Industrial Health 2006; 22: 125-130.

Antioxidant enzyme activities and lipid peroxidation products in heart tissue of subacute and subchronic formaldehyde-exposed rats: a preliminary study.

Objective: The aim of this experimental study was to evaluate the oxidant/antioxidant status and lipid peroxidation in the heart of rats exposed to formaldehyde (FA) inhalation for four weeks (subacute) or 13 weeks (subchronic) continuously. Methods and results: Sixty Wistar albino rats were divided into six groups randomly (ten in each group). The first and second groups were used as subacute and subchronic control groups. FA gas was generated from paraformaldehyde and pumped to a closed glass chamber. Rats were exposed to atmosphere containing 10 and 20 ppm FA (8 h/day, five days per week) during a four and 13 weeks period. After heart tissues were obtained and homogenized, thiobarbituric acid-reactant substances (TBARS) and nitric oxide (NO) levels, as well as superoxide dismutase (SOD) and catalase (CAT) activities, were measured. There were statistically significant findings in SOD and CAT activities in the study groups compared to the control group. Heart tissue SOD level was increased in the group exposed to subacute 10 and 20 ppm FA inhalation compared to the control group (P≤0.011 and ≤0.0001). In addition, heart tissue SOD level was increased in the group exposed to subchronic 10 and 20 ppm FA inhalation compared to the corresponding control group (P≤0.001). On the other hand, there were statistically significant decreases in CAT activity in subacute 10 and 20 ppm groups compared to the corresponding control group (P≤0.012 and ≤0.039, respectively). Although not significant, TBARS levels were increased in both subacute 10 ppm (P=0.100) and subchronic 20 ppm (P=0.053) groups compared to their corresponding control groups. Tissue NO levels were unchanged upon FA inhalation. In the correlation analyses, a meaningful relationship between SOD and CAT activities in subchronic 10 ppm group (r=-0.685, P≤0.029); SOD activity and TBARS level in subchronic 20 ppm group (r=-0.675, P≤0.032); and CAT activity and NO level in subchronic 20 ppm group (r=-0.810, P≤0.005) were found. Conclusion: From the findings of our study, it can be interpreted that subacute and subchronic FA inhalation may stimulate oxidative stress and thus, some secondary toxic effects in cardiac cells and tissue. This increase in the oxidative stress could not induce lipid peroxidation in the membranous structure of cardiac cells. An increased SOD enzyme activity was thought to be secondary to decreased CAT activity, as a compensation mechanism, preventing heart tissue from destruction induced by FA.

The comparison of nail and serum trace elements in patients with epilepsy and healthy subjects.

The objective of this prospective study was to determine the levels of manganese (Mn), copper (Cu), and zinc (Zn) levels in both nail and serum from patients with epilepsy. For this purpose, levels of these elements were measured in 31 patients with epilepsy and 19 healthy subjects. Element analyses were carried out by atomic absorption spectrophotometer (AAS). Increased Mn levels were detected in nail of patients with epilepsy compared to healthy controls (P<.008). The main nail Zn and Cu levels were found to be unchanged in epileptic patients compared to control subjects. There were no significant differences in serum Mn and Zn levels between epileptic patients and control subjects. However, there was a statistically significant increase in serum Cu levels in patients with epilepsy in comparison with control group (P<.009). Our results demonstrate that some trace element levels may vary in epileptic patients, and because of the more stable status, the analysis of these element levels in some tissues such as nail might be superior to serum analysis.

Adenosine deaminase and xanthine oxidase activities in bladder washing fluid from patients with bladder cancer: a preliminary study

Activities of adenosine deaminase (AD), and xanthine oxidase (XO) enzymes were measured in bladder washing fluid (BWF) from 37 patients with bladder cancer. The patients were divided into several groups according to their sex; pattern, number, and depth of the tumors; and tumor grade. There was a statistically significant difference in XO activities between the patients having no tumor and papillary tumor (p < 0.002). The differences in XO values between the patients having no tumor and single tumor; and with no tumor and multiple tumors were statistically significant (p < 0.012, p < 0.016 respectively). XO activities were increased in patients with both papillary and multiple tumors compared to tumor-free group. Regarding to the depth of tumors, only the differences in XO values between the patients having no tumor and superficial tumor was statistically significant (p < 0.037). XO values of patients in grade1 were higher than the patients having no tumor (p < 0.010). AD activities in patients with multiple and invasive tumor were increased compared to patients with single and superficial tumor. AD values in grade 3 were lower than grade 2. However, we did not find any statistically significant differences in AD activities in all groups. As a conclusion, increased XO activity in BWF might be a potentially important finding as an additional diagnostic biochemical tool for bladder cancer. But we could not say this for AD activity. Further investigations in a larger cohort of patients with bladder cancer are needed to enlighten the possible diagnostic role of XO and AD in BWF.

Determination of copper, zinc and manganese in nail and serum from patients with migraine

Metallo-enzymes contain trace elements in their molecular structure to be metabolically active. Manganese-superoxide dismutase (Mn SOD) contains Mn and copper, zinc-superoxide dismutase (Cu, Zn SOD) contains Cu and Zn as prosthetic groups. There have been some studies on the oxidant/antioxidant status of patients with migraine. In the present study, the levels of copper, zinc and manganese in nail and serum were investigated in 53 patients with migraine and 19 healthy subjects. Copper, Zn and Mn levels were measured by atomic absorption spectrophotometry and results obtained were statistically compared. The concentration of Mn in nail and serum was significantly higher in migraine patients than those of control subjects. Although Zn and Cu concentrations in nail were increased in migraine group compared to control group, the difference was not statistically significant. There was a statistically significant increase in Cu level (p < 0.02) and decrease in Zn level in serum from patients with migraine compared to those of control group. The unchanged or increased levels of trace elements, which play important roles as prosthetic groups in SOD, in both nail and serum may suggest that the antioxidant enzyme activities are not negatively affected from the changes. The results obtained are discussed in the light of the literature on the relationship between migraine and trace elements plus antioxidant systems.