4-Phenylbutyric Acid Plus Valproic Acid Exhibits the Therapeutic and Neuroprotective Effects in Acute Seizures Induced by Pentylenetetrazole.

Endoplasmic reticulum (ER) stress and apoptosis are implicated in the pathogenesis of epilepsy. Here we examine the effects of valproic acid (VA) plus 4-phenylbutyric acid (4-PBA) on abnormal electrical brain activity, ER stress and apoptosis in acute seizures induced by pentylenetetrazole (PTZ). Forty male rats were randomly divided into five groups, each consisting of 8 rats as follows: Sham, PTZ, VA+PTZ, 4-PBA+PTZ, and VA plus 4-PBA+PTZ. The treated groups received VA, 4-PBA and VA plus 4-PBA by intraperitoneal application for 7 days prior to PTZ-induced seizure. On the 8th day, acute epileptic seizures were induced by PTZ (50 mg/kg, i.p.) injection, except for the sham group. Then, the seizure stage was observed and ECoG activities were recorded during the 30 min. At 24th post seizures, the hippocampus and blood samples were collected for biochemical and histopathological examinations. Administration of VA plus 4-PBA prior to PTZ-induced seizures significantly decreased seizure stage, the duration of generalized tonic-clonic seizure and the total number of spikes as increased the latency to the first myoclonic jerk when compared to the PTZ group. 4-PBA suppressed the increased levels of ER stress markers GRP78 and CHOP in the hippocampus. VA plus 4-PBA treatment before seizures significantly inhibited PTZ-induced elevations of apoptosis-related indicators caspase-3 and caspase-12, and significantly reduced the number of histopathological lesions of the hippocampus region at 24th post seizures. These findings suggest that administration of VA plus 4-PBA prior to PTZ-induced seizures may be involved in the neuroprotective potential of these agents for seizures.

The effects of silymarin plus glutathione on the prevention of liver ischemia-reperfusion injury

Abstract Liver ischemia-reperfusion (IR) injury is a major clinical trouble encountered in clinical practice. This study aimed to examine the therapeutic effects of silymarin (SM) plus glutathione (GSH) on hepatic IR injury using a rat model of liver IR. Fifty male rats were randomly divided into five groups, each consisting of 10 rats as follows: Sham, IR, SM-IR, GSH-IR and SM plus GSH-IR. All groups except sham were subjected to 30-min ischemia and 24-h reperfusion. The treated groups received 100 mg/kg of SM, GSH and a mixture of SM plus GSH, 60 min prior to the IR. After a period of 24 h, blood and liver samples were collected for biochemical and histopathological evaluations. Pretreatment with SM, GSH and SM plus GSH before hepatic IR significantly decreased IR-induced elevations of aminotransferases, and significantly reduced the histopathological damage scores of the liver in the late phase of IR injury. Moreover, SM plus GSH treatment prior to liver IR significantly suppressed inflammatory process and oxidative stress as demonstrated by attenuations in tumor necrosis factor-α, myeloperoxidase and the thiobarbituric acid-reactive substances. These findings suggest that administration of SM plus GSH prior to liver IR may protect the liver parenchyma from the effects of an IR injury

Pentraxin 3, ischemia-modified albumin, and myeloperoxidase in predicting a cardiac damage in acute carbon monoxide poisoning.

BACKGROUND: Carbon monoxide (CO) poisoning is associated with cardiac injuries or manifestations, frequently attributing to direct hypoxic damage at cellular level. For this, the aims were to evaluate the role of serum pentraxin 3 (PTX 3), ischemia-modified albumin (IMA), and myeloperoxidase (MPO) as an early biomarker for cardiac damage when compared to cardiac troponin I (cTnI) and creatine kinase-MB fraction (CK-MB) in adult patients with acute CO poisoning. METHODS: Forty patients with acute CO poisoning admitted to the emergency department. The patients were divided into 2 main groups as follows: cardiac injury (group I, n=19) and nonsuspected cardiac injury (group II, n=21). Pentraxin 3, IMA, MPO, cTnI, CK-MB, and the other assays in the circulation were measured on admission. RESULTS: Upon measuring the serum PTX 3, IMA, MPO, cTnI, and CK-MB levels as well as large electrocardiography and echocardiography abnormalities of patients with cardiac injury on admission, no statistical difference for PTX 3, IMA, and MPO was found between the groups (P>.05). However, cTnI, CK-MB, and leukocyte count (white blood cell) were higher determined in patients of group I compared to group II (P<.05). Receiver operating characteristic curve was also performed to evaluate the diagnostic performance of these tests in patients with cardiac injury. CONCLUSIONS: Our results suggest that PTX, IMA, and MPO assays are not superior to cTnI and CK-MB in predicting a cardiac damage in patients with acute CO intoxication.

An Update on Ovarian Aging and Ovarian Reserve Tests.

Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs) provide an indirect estimate of a female's diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs.

Ischemia-modified albumin is not better than creatine kinase-MB and cardiac troponin I in predicting a cardiac injury in nontraumatic subarachnoid hemorrhage.

BACKGROUND: The aims were to investigate the role of serum ischemia-modified albumin (IMA), tumor necrosis factor α (TNF-α), and myeloperoxidase (MPO) and to evaluate the relationship between IMA and cardiac markers (creatine kinase myocardial isoenzyme [CK-MB] and cardiac troponin I [cTnI]) related to cardiac abnormalities in adult patients after nontraumatic subarachnoid hemorrhage (SAH). METHODS: Twenty-nine patients with nontraumatic SAH admitted to the emergency department and 20 healthy adults as the control group were included in the study. Ischemia-modified albumin, TNF-α, MPO, CK-MB, cTnI, and leukocyte count (white blood cell [WBC]) in the circulation were measured on admission. RESULTS: Ischemia-modified albumin, TNF-α, and MPO levels were higher by mean values of 11.6%, 9.5%, and 2.9%, respectively, in patients with SAH compared with control group. However, levels of these parameters were not statistically different between the groups (P > .05). However, WBC, CK-MB, and cTnI values were significantly higher in patients with SAH compared with healthy control (P < .001, P < .01, and P < .05, respectively). White blood cell and cTnI levels in the circulation were positively correlated with patients' clinical severity (r = 0.598, P = .001 and r = 0.461, P = .012, respectively). Ischemia-modified albumin has a poor diagnostic value in comparison with WBC, CK-MB, and cTnI tests to differentiate between patients after SAH and controls according to receiver operating characteristic curve. CONCLUSIONS: The results suggest that IMA is not better than CK-MB and cTnI in predicting a cardiac injury in patients after nontraumatic SAH.

Heart-type fatty acid-binding protein as a potential biomarker of acute carbon monoxide poisoning.

BACKGROUND: The aim of this study was to investigate the role of serum heart-type fatty acid-binding protein (H-FABP) in the evaluation of patients with carbon monoxide (CO) poisoning. METHODS: Forty patients with acute CO poisoning admitted to the emergency department and 15 healthy adults as the control group were included in the study. Serum H-FABP levels of patients were studied on admission and at the 6th, 12th, and 18th hours. Patients were divided into 3 groups according to clinical severity as mild, moderate, and severe. Patients were also divided into 2 groups according to treatment with hyperbaric oxygen (HBO) or normobaric oxygen. RESULTS: Serum H-FABP levels of the patients were higher than those of the control group. There was a negative correlation between H-FABP levels and Glasgow Coma Scale score on admission. Heart-type fatty acid-binding protein levels were significantly higher in patients in the severe compared with mild group. Heart-type fatty acid-binding protein levels in patients treated with HBO were significantly higher than in those treated with normobaric oxygen. The cutoff value of serum H-FABP as an indicator for HBO treatment was determined as 1.5 ng/mL or higher, with a sensitivity of 85.7% and specificity of 69.7%. Serial measurement revealed that H-FABP level peaked at the sixth hour and reduced over time but remained higher than in the control group at the 18th hour. CONCLUSION: Heart-type fatty acid-binding protein may be a promising novel biomarker in the evaluation of clinical severity and in the selection of patients for HBO therapy in acute CO poisoning.

Hsp 70, hsCRP and oxidative stress in patients with acute coronary syndromes.

Acute coronary syndromes (ACS) like unstable angina (UA) and acute myocardial infarction (AMI) can lead to the morbidity and mortality. The diagnosis and management of patients with ACS in the earliest times after symptom onset are considerably important in the emergency service. Study aimed to investigate the serum levels of heat shock protein 70 (Hsp 70), high sensitivity C-reactive protein (hsCRP), total creatine kinase (CK) activity, creatine kinase MB (CK-MB), cardiac troponin I (cTnI), leukocyte count (WBCs) and markers of oxidative stress in the first hours of ACS and to view their diagnostic values. 70 patients with ACS after admission and 20 sex-matched healthy controls were included in this study. Serum Hsp 70, hsCRP, CK, CK-MB, cTnI, protein carbonyls, malondialdehyde as well as whole blood WBCs were measured. The level of hsCRP was statistically higher in patients with AMI and UA than that of control group (p<0.001). WBCs and oxidized protein levels were higher in AMI than in UA and control groups. cTnI was related to CK-MB in AMI and UA groups (r=0.731, r=0.806, p<0.001, respectively) and also related with hsCRP in UA group (r=0.824, p<0.001). The mean Hsp 70 level was higher by 32.2% in AMI and 12.7% in UA patients compared to control subjects. hsCRP may have a role in the inflammatory response after ACS. In addition to cTnI and CK-MB, WBCs and hsCRP may be useful as a marker for the identification of ACS patients with chest pain in early diagnosing.

Protective effects of etanercept and methylprednisolone on pancreatic damage in cerulein-induced acute pancreatitis.

OBJECTIVE: To examine the pharmacological effect of etanercept and methylprednisolone (MP) on acute pancreatitis (AP) induced by cerulein in an experimental rat model. METHODS: The present study was carried out in the Experimental Research Center, Ondokuz Mayis University, Samsun, Turkey between December 2008 and October 2009. Forty adult Sprague-Dawley rats were divided into 5 groups (n=8): 1--sham, 2--cerulein induced pancreatitis (over 20 hours), 3--etanercept (5 mg/kg, intraperitoneal), 4--MP (10 mg/kg, intramuscular), 5--etanercept plus MP. The rats in groups 3, 4, and 5 were cerulein-induced pancreatitis at 20 hours, as well. After the treatment, the pancreas and blood were taken for histopathological and biochemical analysis. RESULTS: All cerulein-treated rats developed biochemical and histopathological AP after 20 hours. Histological findings of pancreatitis and serum levels of amylase and lipase were lower in group 5 compared to group 2. Pancreatic inflammation and total pathological score were statistically reduced in the tissues of the pancreas at 20 hours after the treatment of etanercept plus MP in group 5 compared to groups 2, 3, and 4. CONCLUSION: In the early stage of cerulein induced AP, the administration of etanercept plus MP attenuated pancreatic inflammation and significant damage in rats.

Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats.

A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine-methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg(-1) body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg(-1) body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant-supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant-supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol-treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l-cys/l-met along with ethanol attenuated the amount of oxidation which suggested that cysteine-methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion.

Does ascorbate/L-Cys/L-Met mixture protect different parts of the rat brain against chronic alcohol toxicity?

Chronic ingestion of high levels of alcohol may cause oxidative stress that results in the formation, through alcohol metabolism, of excess free radicals, acetaldehyde, lipid and protein oxidation, and their reactivity products. These harmful molecules may trigger oxidative damage to neurons and can cause cell death. It is hypothesized that cysteine-methionine and vitamin C may neutralize these harmful compounds while potentiating the antioxidant capacity of the cell or tissue. In the present study, rats were fed regular diets and were maintained for 90 days in (1) the control group, (2) the alcoholic group, which was given 2.5 g of 50% ethanol/kg body weight administered intragastrically every other day, or (3) the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol/kg body weight + a solution that contained 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine was administered intragastrically every other day. The mean blood alcohol level was raised by 40% in the alcoholic group compared with the control group, but, compared with the alcoholic group, the alcohol level was decreased by 30% in the antioxidant-supplemented group. In keeping with blood alcohol levels, oxidized protein and lipid content in the cerebrum, brain stem, and cerebellum were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. The mean total thiol level was higher in the antioxidant-supplemented group than in the alcoholic and control groups. It is interesting to note that the level of total glutathione in the cerebrum and cerebellum in the alcoholic group was lower than in the control and antioxidant-supplemented groups. In conclusion, long-term alcohol administration led to increased levels of oxidized protein and lipids in the cerebrum, brain stem, and cerebellum of rats. Simultaneous intake of ascorbate/l-cys/l-met and ethanol attenuated the amount of oxidation that occurred, which suggested that cysteine, methionine, and vitamin C may play a protective role in the central nervous system against oxidative damage caused by alcohol consumption. In addition, the mean alcohol level was increased in the alcoholic group compared with the control group. The level of total glutathione was significantly decreased in the cerebellum of the alcoholic group, and oxidative damage was noted in various parts of the brain in this group. These findings suggest that oxidative stress plays a pathogenetic role in brain damage related to chronic alcoholism.

Alcohol-induced oxidative stress and reduction in oxidation by ascorbate/L-cys/ L-met in the testis, ovary, kidney, and lung of rat.

Chronic exposure to high doses of alcohol results in many pathophysiologic changes in cellular function caused by the alcohol itself and the effects of its metabolism (ie, generation of acetaldehyde, nicotinamide adenine dinucleotide [NADH], free radicals, and oxidative stress). However, the role of each of these effects on the testis, ovary, kidney, and lung in chronic alcoholism must be investigated. It is hypothesized that cysteine-methionine and vitamin C might neutralize harmful compounds and potentiate the antioxidant capacity of the cell or tissue. In this study, rats were fed regular diets and were maintained in the following groups for 90 days: control group; alcoholic group (2.5 g of 50% ethanol/kg body wt administered intragastrically every other day); and alcoholic with antioxidant supplement group (2.5 g of 50% ethanol plus a solution containing 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine/kg body wt administered intragastrically every other day). After treatment had been completed, rat blood, testis, ovary, kidney, and lung were taken for biochemical analysis. Mean alcohol level in the alcoholic group was raised (by 40%) compared with that in the control group, but it was lower (by 30%) in the antioxidant-supplemented group than in the alcoholic group. In accordance with the levels of alcohol, oxidized protein and lipid content in the testis, ovary, kidney, and lung were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. It is interesting to note that levels of glutathione in the testis and lung of the alcoholic group were lower than those in both the control and antioxidant-supplemented groups. In conclusion, chronic alcohol administration led to a significant increase in the level of protein oxidation in the ovary and kidney of rats. Simultaneous intake of ascorbate/L-cys/L-met, along with ethanol, partly attenuated the amount of lipid and protein oxidation that occurred in tissues with oxidative stress caused by alcohol consumption.

The effects of ethanol consumption on the lipid peroxidation and glutathione levels in the right and left brains of rats.

The effects of ethanol consumption on the levels of lipid peroxidation and reduced glutathione (GSH) in the cerebral hemispheres of male rats were investigated. The rats were randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups, and four groups given vitamin E. The level of lipid peroxidation increased 34.32% (right brain), 35.67% (left brain) in 10% ethanol-consuming rats; 32.05% (right brain), 31.81% (left brain) in 25% ethanol-consuming rats; and 33.45% (right brain), 39.72% (left brain) in 35% ethanol-consuming rats. The GSH level of the right and left brains significantly decreased: 19.39%, 19.56%; 27.58%, 29.34%; 35.34%, 33.22% in rats consuming 10%, 25%, and 35% ethanol, respectively. These effects were partly antagonized by administration of vitamin E (100 mg/kg/day i.p.) to ethanol-consuming rats for 20 days. The results suggested that the cerebral hemispheres of adult rats are susceptible to the oxidative neurotoxic effects of ethanol, which may be blocked by vitamin E.

Moderate hypothermia prevents brain stem oxidative stress injury after hemorrhagic shock.

BACKGROUND: The purpose of this study was to investigate the effects of temperature on oxidative stress in brain stem tissue induced by hemorrhagic shock. We researched the hemorrhagic oxidative stress at various core temperatures using reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) as markers of lipid peroxidation in brain stem homogenate. METHODS: Forty rats were divided into four groups, of which one constituted the nonbleeding normothermia control group. In all of the three study groups, 40% of estimated blood volume was removed while they were being held at normothermia, mild hypothermia (32 degrees C), or moderate hypothermia (28 degrees C). Parameters including mean arterial pressure, rectal temperature, and heart and breathing rates were monitored and recorded during the procedures. After an hour at shock state, tissue samples were removed by craniectomy. RESULTS: The tissue levels of TBARS increased significantly in normothermic and mild hypothermic hemorrhagic shock groups (10.74 nmol/g and 8.26 nmol/g) as compared with the control group (3.50 nmol/g) (p < 0.001). However, the tissue TBARS level in the moderate hypothermia group was only minimally increased (4.53 nmol/g). GSH showed a slight decrease in normothermic and mild hypothermic bleeding rats, and were unchanged in the moderate hypothermic rats. CONCLUSION: Moderate systemic hypothermia (28 degrees C) appears to protect brain stem tissue from oxidative stress during severe hemorrhagic shock in rats, as indicated by insignificant change in tissue TBARS and GSH concentrations. These results suggest antioxidant protective effects of moderate systemic hypothermia in metabolically active brain stem tissue during hemorrhagic shock. Similar effects in humans remain to be studied.

Effectiveness of free radicals in hydatid cysts.

The lipid peroxidation (tbars) levels of fertile cyst liquids (0.84+/-0.14, 0.9+/-0.12 micromol/L) for sheep liver and lung, respectively, were higher than infertile cyst liquids (0.29+/-0.07, 0.20+/-0.06 micromol/L) for sheep liver and lung (p < 0.05). There were no significant differences between fertile cyst membranes (0.71+/-0.12, 0.74+/-0.27 nmol/mg wet tissue protein for liver and lung, respectively) and infertile cyst membranes (0.37+/-0.11, 0.39+/-0.15 nmol/mg wet tissue protein) in terms of tbars levels (p > 0.05). The lipid peroxidation levels determined for protoscoleces (1.99+/-0.45, 2.07+/-0.20 nmol/mg wet tissue protein for sheep liver and lung, respectively) were significantly higher than those of fertile cyst membranes (p < 0.05) and than those of infertile cyst membranes (p < 0.01). NO levels of cattle fertile hydatid liquids (liver nitrite; 2.07+/-0.73 nmol/L, liver nitrate; 4.01+/-1.15 micromol/L, lung nitrite; 2.44+/-0.70 umol/L, lung nitrate; 0.87+/-0.30 micromol/L) were significantly higher compared to cattle infertile hydatid liquids (liver nitrite; 0.66+/-0.29 micromol/L, liver nitrate; 1.10+/-0.41 umol/L, lung nitrite; 0.55+/-0.15 micromol/L, lung nitrate; 0.54+/-0.16 micromol/L) (p < 0.05).