Uncatalyzed Condensation Reactions between Aromatic Aldehydes and Thiobarbituric Acid in Water

A series of 5-arylidene thiobarbituric acids were prepared from aromatic aldehydes and thiobarbituric acid in water without catalyst conditions in good yields. The structures were characterized by elemental analysis, IR and 1H NMR spectra.

Measurement of Malondialdehyde as a Biomarker of Lipid Oxidation in Fish

Oxidative reactions are key part of the stress response in marine organisms, which are exposed to a wide variety of environmental stressors. Lipid peroxidation (LPO) occurs in response to oxidant attack, giving rise to unsaturated aldehydes as malondialdehyde (MDA), the main biomarker for LPO assessment. Levels of MDA are measured in biological samples of different fish matrices to determine the oxidative effect of physical or chemical agents, particularly represented by metals. The most used assay is the spectrophotometric determination of thiobarbituric acid (TBA) as MDA-TBA2 adduct. Selectivity is enhanced by separating the adduct by chromatographic methods such as high-performance liquid chromatography or by using alternative derivatization reagents. Because, in biological organism, MDA is found free or protein bound, the two forms should be measured, and the extraction procedures are a crucial step in the processing of the biological sample. This review focused on MDA determination procedures used to assess the effect of experimental and environmental stress induced in fish.

Protective effect of estradiol on hepatocytic oxidative damage

AIM: To examine the protective effect of estradiol on the cultured hepatocytes under oxidative stress. METHODS: Hepatocytes of rat were isolated by using perfusion method, and oxidative stress was induced by a serum-free medium and FeNTA. MDA level was determined with TBA method. Cell damage was assessed by LDH assay. Apoptosis of hepatocytes was assessed with cytoflowmetric analysis. Expression of Bcl-xl in cultured hepatocytes was detected by Western blot. The radical-scavenging activity of estradiol was valued by its ability to scavenge the stable free radical of DDPH. RESULTS: Oxidative stress increased LDH from 168 +/- 25 x 10(-6)IU.cell(-1) to 780 +/- 62 x 10(-6)IU.cell(-1) and MDA(from 0.28 +/- 0.07 x 10(-6)nmol.cell(-1) to 1.35 +/- 0.12 x 10(-6)nmol.cell(-1)) levels in cultured hepatocyte, and estradiol inhibited both LDH and MDA production in a dose dependent manner. In the presence of estradiol 10(-6)mol.L(-1), 10( -7 )mol.L(-1) and 10(-8)mol.L(-1),the LDH levels are 410 +/- 53 x 10(-6)IU.cell(-1) (P【0.01 vs oxidative group), 530 +/- 37 X 10(-6)IU.cell(-1 ) (P【0.01 vs oxidative group), 687+/-42 x 10(-6)IU.cell(-1) (P【0.05 vs oxidative group) respectively, and the MDA level are 0.71+/-0.12 x 10(-6)nmol.cell(-1) (P【0.01 vs oxidative group),0.97+/-0.11 x 10(-6)nmol.cell(-1 )(P【0.01 vs oxidative group) and 1.27+/-0.19 x 10(-6)nmol.cell(-1) respectively. Estradiol suppressed apoptosis of hepatocytes induced by oxidative stress, administration of estradiol(10(-6)mol/L)decreased the apoptotic rate of hepatocytes under oxidative stress from 18.6 +/- 1.2% to 6.5 +/-2.5%, P【0.01. Bcl-xl expression was related to the degree of liver cell damage due to oxidative stress, and estradiol showed a protective action. CONCLUSION: Estradiol protects hepatocytes from oxidative damage by means of its antioxidant activity.

Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis

AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP).Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation.METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done.RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO.CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.

N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat

AIM: There is increasing evidence that alcohol-induced liverdamage may be associated with increased oxidative stress.We aimed to investigate free-radical scavenger effect of n-acetylcysteine in rats intragastrically fed with ethanol.METHODS: Twenty-four rats divided into three groups werefed with ethanol (6 g/kg/day, Group 1), ethanol and n-acetylcysteine (1 g/kg, Group 2), or isocaloric dextrose(control group, Group 3) for 4 weeks. Then animals weresacrificed under ether anesthesia, intracardiac blood andliver tissues were obtained. Measurements were performedboth in serum and in homogenized liver tissues.Malondialdehyde (MDA) level was measured by TBARSmethod. Glutathione peroxidase (GSH-Px) and superoxidedismutase (SOD) levels were studied by commercial kits.Kruskal-Wallis test was used for statistical analysis.RESULTS: ALT and AST in Group 1 (154 U/Land 302 U/L,respectively) were higher than those in Group 2 (94 U/L and155 U/L) and Group 3 (99 U/L and 168 U/L) (P＝0.001 forboth). Serum and tissue levels of MDA in Group 1 (1.84 nmol/mL and 96 nmol/100 mg-protein) were higher than Group 2(0.91 nmol/mL and 64 nmol/100 mg-protein) and Group 3(0.94 nmol/mL and 49 nmol/100 mg-protein) (P＜0.001 forboth). On the other hand, serum GSH-Px level in Group 1(8.21 U/g-Hb) was lower than Group 2 (16 U/g-Hb) andGroup 3 (16 U/g-Hb) (P＜0.001). Serum and liver tissue levelsof SOD in Group 1 (11 U/mL and 26 U/100 mg-protein)were lower than Group 2 (18 U/mL and 60 U/100 mg-protein)and Group 3 (20 U/mL and 60 U/100 mg-protein) (P＜0.001for both).CONCLUSION: This study demonstrated that ethanol-induced liver damage is associated with oxidative stress,and co-administration of n-acetylcysteine attenuates thisdamage effectively in rat model.

Assessment of oxidative stress in chronic pancreatitis patients

AIM: To assess the levels of antioxidant capacity and oxidative damage in blood of chronic pancreatitis (CP) patients in comparison with those in healthy control sub- jects, by using several different analytical techniques. METHODS: Thirty-five CP patients and 35 healthy con- trol subjects were investigated prospectively with re- spect to plasma levels of thiols, ferric reducing ability of plasma (FRAP, i.e. antioxidant capacity), levels of protein carbonyls and thiobarbituric acid reactive substances (TBARS). Additionally, we evaluated the production of reactive oxygen species (ROS) in whole blood. RESULTS: The antioxidative thiols including cysteine, cysteinylglycine and glutathione were significantly lower in CP patients. In addition, the non-enzymatic antioxi- dant capacity was significantly lower in CP patients, which correlated with the amount of oxidative protein (protein carbonyls) and the extent of lipid damage (TBARS), both were significantly higher in CP patients. The ROS production in whole blood after stimulation with phorbol 12-myritate 13-acetaat, demonstrated a strong tendency to produce more ROS in CP patients. CONCLUSION: Oxidative stress may contribute to the pathogenesis of chronic pancreatitis by decreasing anti- oxidant capacity and increasing oxidative damage in CP patients may be a rationale for intervention with antioxi- dant therapy.

Biochemical responses of freshwater fish Carassius auratus to polycyclic aromatic hydrocarbons and pesticides

The freshwater fish Carassius auratus was chosen as an experimental subject, and their hepatic biochemical responses to the medium-term exposure of Benzo（k）fluoranthene （BkF） alone and in combination with PCB 118 and dichlorodiphenyltrichloroethane （DDT） were investigated by measuring the reduced glutathione （GSH）, glutathione S-transferase （GST）, and thiobarbituric acid reactive substances （TBARS）, to assess sublethal effects. The hepatic GSH content was significantly inhibited by organic pollutants, alone and in mixtures, while the TBARS content was significantly induced after three days of exposure. Bell-shaped concentration-response charts of GST activities were obtained. Significant dose-response relationships were found for hepatic GSH and TBARS contents of all concentrations and for the GST activity, except at the highest concentration. The GSH content, GST activity, and TBARS content in Carassius auratus were confirmed as useful biomarkers of exposure to organic pollutions.

Neuroprotective role of antioxidant and pyranocarboxylic acid derivative against AlCl_(3) induced Alzheimer’s disease in rats

Objective:To assess potential of quercetin and etodolac to treat oxidative stress in neuronal death and inflammation in Alzheimer’s disease of AlCl3 induced rat models.All results of this AlCl_(3)model are compared with those obtained in controls.Methods:Wistar rats,housed in a controlled environment were treated with aluminum chloride(4.2 mg/kg of body weight,i.p.)for 28 d rather than oral to ensure neurotoxic concentration in hippocampus and hypothalamic region,part highly active in memory control and cognition,while control group was injected with saline.Estimation of thiobarbituric acid reactive substance,superoxide dismutase,reduced glutathione and acetylcholine levels gave estimation of neuronal damage.Low(20 mg/kg and 25 mg/kg)and high(40 mg/kg and 50 mg/kg)doses of quercetin and etodolac were administered to the test groups respectively.Histopathology study was conducted to perform relative study.Results:Co-administration of quercetin and etodolac either alone or in combination prevented the changes in biochemical markers of Alzheimer’s disease,but significant results(P<0.05)were seen when a combination of two was administered at low dose levels.Good correlation was developed between chemical estimations and histopathology study.Conclusions:Our findings suggest a combined role of anti-oxidant and cyclooxygenase inhibitor in protection of neural degeneration and inflammation due to oxidative stress.

Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies

Bis-thiobarbiturate derivatives 1-15 have been synthesized, characterized by 1HNMR and El-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with iC50 values ranging 7.45 ± 0.12 - 74.24 ± 0.81 μmol/L while the standard thiourea behaved normally （ICso = 21.10 ±0.12）. Compounds I （IC50= 7.45 ± 0.12 ]μmol/L）, 9 （IC50 =18,17 ± 1.03 bmol/L） and 13 （IC50= 8.61 ± 0.45 bmol/L） showed excellent urease inhibitory activity in the series. Molecular modeling studies were performed to understand the binding site with the bimetallic nickel center of the enzyme. Structure-activity relationship has also been established for these compounds. This study identified bis- thiobarbiturate as a novel class of urease inhibitors.