Mehmet Ibrahim Turan

An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine Thiamine and thiamine pyrophosphate effects on cisplatin neurotoxicity

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.

Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients

The purpose of this study was to investigate the effect of supplementary vitamin D therapy in addition to amitriptyline on the frequency of migraine attacks in pediatric migraine patients. Fifty-three children 8-16 years of age and diagnosed with migraine following the International Headache Society 2005 definition, which includes childhood criteria, were enrolled. Patients were classified into four groups on the basis of their 25-hydroxyvitamin D [25(OH)D] levels. Group 1 had normal 25(OH)D levels and received amitriptyline therapy alone; group 2 had normal 25(OH)D levels and received vitamin D supplementation (400 IU/day) plus amitriptyline; group 3 had mildly deficient 25(OH)D levels and received amitriptyline plus vitamin D (800 IU/day); and group 4 had severely deficient 25(OH)D levels and was given amitriptyline plus vitamin D (5000 IU/day). All groups were monitored for 6 months, and the number of migraine attacks before and during treatment was determined. Calcium, phosphorus alkaline phosphatase, parathormone, and 25(OH)D levels were also determined before and during treatment. Results were compared between the groups. Data obtained from the groups were analyzed using one-way analysis of variance. The number of pretreatment attacks in groups 1 to 4 was 7±0.12, 6.8±0.2, 7.3±0.4, and 7.2±0.3 for 6 months, respectively (all P>0.05). The number of attacks during treatment was 3±0.25, 1.76±0.37 (P<0.05), 2.14±0.29 (P<0.05), and 1.15±0.15 (P<0.05), respectively. No statistically significant differences in calcium, phosphorus, alkaline phosphatase, or parathormone levels were observed (P>0.05). Vitamin D given in addition to anti-migraine treatment reduced the number of migraine attacks.

Protective effect of nimesulide against hepatic ischemia/reperfusion injury in rats: effects on oxidant/antioxidants, DNA mutation and COX-1/COX-2 levels.

BACKGROUND Nimesulide is a pharmacological agent and selective COX-2 inhibitor. It has anti-inflammatory, analgesic and antipyretic properties. The purpose of this study was to investigate the effect of nimesulide on oxidant/antioxidant, DNA mutation and COX-1/COX-2 activities in rat liver tissue with induced ischemia/reperfusion (I/R). METHODS Before the experiment, rats were divided into four groups; liver ischemia/reperfusion (LIR), 50mg/kg nimesulide+liver ischemia/reperfusion (NLIR50), 100mg/kg nimesulide+liver ischemia/reperfusion (NLIR100) and a control group to be given a sham operation (SG). Malondialdehyde (MDA), total glutathione (GSH) levels and myeloperoxidase (MPO), COX-1/COX-2 enzyme activities and DNA damage product level results from liver tissues and serum AST and ALT levels were determined. The data obtained were compared with the results from the liver ischemia/reperfusion and sham operation groups. RESULTS MDA levels, MPO and COX-2 activities and products of DNA injury were significantly lower in the groups given nimesulide, and particularly the NLIR100 group, compared to the LIR group (p<0.05), while tGSH levels were significantly higher (p<0.05). There was no significant difference between the NLIR50 and NLIR100 groups and the LIR group in terms of COX-1 levels (p>0.05). AST and ALT levels were significantly lower in the other groups compared to the LIR group (p<0.05). CONCLUSIONS Nimesulide at 100mg/kg prevented oxidative liver damage induced with I/R significantly better than at a dose of 50mg/kg. These experimental findings indicate that nimesulide may be useful in the treatment of hepatic I/R damage.

Antioxidant Status in Blood of Obese Children: The Relation between Trace Elements, Paraoxonase, and Arylesterase Values

Obesity is known to lead to complications involving several systems. The basic mechanism in obesity-related complications is chronic inflammation and increased oxidative stress. Trace element levels in obese children may vary due to poor nutritional habits. The purpose of this study was to investigate the relation between serum paraoxonase (PON1) and arylesterase (ARE) levels, markers of the oxidant–antioxidant balance in the body, and serum zinc (Zn), copper (Cu), manganese (Mn), and selenium (Se) concentrations in obese children. Fifty-seven overweight patients aged 6–17 and 48 age- and sex-matched healthy children were included in the study. Serum PON1 and ARE activity levels were measured, together with Cu, Zn, Mn, Se, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, glucose, aspartate amino transferase, and alanine amino transferase levels. PON1 and ARE activity levels were significantly lower in obese patients compared to those in healthy individuals (P < 0.05). Various changes were determined in Cu, Zn, Mn, and Se levels between the study and control groups (P < 0.05). In terms of the relation between trace elements and PON1 and ARE levels, a significant positive correlation was determined between serum Se and PON1 levels in the study group (P < 0.05, r = 0.31). No significant correlation was determined between other trace element levels and PON1 and ARE levels (P > 0.05). In conclusion, the detection in our study of a positive correlation between Se and PON1 levels in obese children may be significant in terms of showing a relation between Se and antioxidant systems in obese children.

Benefits of the antioxidant and anti‐inflammatory activity of etoricoxib in the prevention of ovarian ischemia/reperfusion injury induced experimentally in rats

This study is a biochemical investigation of the effect of etoricoxib, a selective cyclooxygenase (COX)‐2 inhibitor, on ischemia/reperfusion (I/R) injury experimentally induced in rat ovaries.

An examination of the mutual effects of valproic acid, carbamazepine, and phenobarbital on 25-hydroxyvitamin D levels and thyroid function tests.

BACKGROUND The effects of antiepileptic drugs (AEDs) on bone metabolism and the endocrine system are not fully known, and publications on the subject are inconsistent. OBJECTIVE The study aimed to examine the mutual effects of valproic acid (VPA), carbamazepine (CBZ), and phenobarbital (PB)-AEDs frequently used in childhood-on bone mineral metabolism and thyroid function tests. PATIENTS AND METHODS Children monitored with a diagnosis of idiopathic epilepsy by the pediatric neurology clinic, using AEDs for at least 6 months and with episodes under control, were included in the study. Patients were divided into groups on the basis of the drugs used. Thyroid function tests and 25-hydroxyvitamin D or 25(OH)D levels were measured from blood specimens. The data obtained were then compared with those of the control group. RESULTS A significantly high level of subclinical hypothyroidism was seen in patients using VPA (p < 0.001). There was no significant difference between any of the three study groups and the control group in terms of 25(OH)D (p > 0.05). CONCLUSIONS Pediatric patients using AEDs, particularly VPA, should be monitored for subclinical hypothyroidism. VPA, CBZ, and PB have no effect on vitamin D levels.

Use of thiamine pyrophosphate to prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary

OBJECTIVE To investigate whether thiamine pyrophosphate can prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary. Biochemical examinations of the ovaries were also performed. STUDY DESIGN Rats were divided into two main groups of three subgroups each. An ischemia reperfusion model was established in the first main group, while surgical unilateral ovariectomy was performed in the second. Thiamine pyrophosphate and melatonin were administered to the subgroups. No additional procedure was performed in the control groups. The rats were then left in laboratory environments and their fertility levels were determined. Malondialdehyde, total glutathione and DNA damage products were measured in those rats from which ovarian tissue was collected. RESULTS The results showed that thiamine pyrophosphate prevented ischemia/reperfusion injury-related infertility, but melatonin did not provide adequate prevention. However, reproduction in healthy animals receiving melatonin began earlier compared to those receiving thiamine pyrophosphate. Melatonin suppressed oxidative stress caused by ischemia/reperfusion in ovarian tissue significantly better than did thiamine pyrophosphate. CONCLUSIONS We think that different mechanisms, in addition to antioxidant activity, are involved in the prevention of reperfusion-associated infertility after ischemia.

The protective effect of thiamine pyrophosphate, but not thiamine, against cardiotoxicity induced with cisplatin in rats

Abstract This study investigated the effect of thiamine pyrophosphate on oxidative damage associated with cardiotoxicity caused by cisplatin (CIS), an antineoplastic agent, in rats, and compared this with thiamine. Animals used in the study were divided into four groups of 6 rats each. These represented a control group receiving 5 mg/kg of CIS, study groups receiving 20 mg/kg of thiamine pyrophosphate plus 5 mg/kg of cisplatin (CTPG) or 20 mg/kg of thiamine plus 5 mg/kg of cisplatin and a healthy (H) group. All doses were administered intraperitoneally once a day for 14 days. Malondialdehyde, total glutathione and products of DNA injury results were similar in the CTPG and H groups (p > 0.05). Creatinine kinase, creatine kinase MB and troponin 1 levels were similar in the CTPG and H groups (p > 0.05). Thiamine pyrophosphate prevented CIS-associated oxidative stress and heart injury, whereas thiamine did not prevent these.

Thyroid functions and trace elements in pediatric patients with exogenous obesity.

Obesity is a multifactorial disease developing following impairment of the energy balance. The endocrine system is known to be affected by the condition. Serum thyroid hormones and trace element levels have been shown to be affected in obese children. Changes in serum thyroid hormones may result from alterations occurring in serum trace element levels. The aim of this study was to evaluate whether or not changes in serum thyroid hormone levels in children with exogenous obesity are associated with changes in trace element levels. Eighty-five children diagnosed with exogenous obesity constituted the study group, and 24 age- and sex-matched healthy children made up the control group. Serum thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (TG), selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn) levels in the study group were measured before and at the third and sixth months of treatment, and once only in the control group. Pretreatment fT4 levels in the study group rose significantly by the sixth month (p = 0.006). Zn levels in the patient group were significantly low compared to the control group (p = 0.009). Mn and Se levels in the obese children before and at the third and sixth months of treatment were significantly higher than those of the control group (p = 0.001, p = 0.001). In conclusion, fT4, Zn, Cu, Mn, and Se levels are significantly affected in children diagnosed with exogenous obesity. The change in serum fT4 levels is not associated with changes in trace element concentrations.

Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity.