Effects of ammonia and allopurinol on rat hippocampal NMDA receptors.

Ammonia is considered to be the main agent responsible for hepatic encephalopathy which progressively leads to altered mental status. N-methyl-D-aspartate (NMDA) is an ionotropic glutamate receptor, which is involved in synaptogenesis, memory and neurotoxicity. The aim of this study was to investigate the effects of ammonia intoxication and allopurinol, a xanthine oxidase (XO) inhibitor, on NMDA receptor subunits, NR2A and NR2B, in the hippocampus of rats. Thirty-six male rats were divided into three groups (n = 12/group) as follows: (1)control group (phosphate buffered saline (PBS) solution); (2)ammonia group (ammonium acetate, 2.5 mmol/kg), (3)ammonia + allopurinol group (ammonium acetate, 2.5 mmol/kg, allopurinol, 50 mg/kg). Each rat received intraperitoneal injection for 28 days. Western Blotting technique was used for detecting NR2A and NR2B expressions. Both NR2A and NR2B subunit expressions decreased 27 and 11%, respectively, in ammonia group with respect to the control group. Ammonium acetate decreased significantly in NR2A subunit expressions in the hippocampus (p < 0.01). Administration of ammonia + allopurinol caused statistically significant increases in NR2A subunit expressions compared to the ammonia group (p < 0.001). The down-regulation of NMDA receptors caused by ammonium acetate suggest that these receptors may play role in the process of hepatic encephalopathy and using allopurinol may have some protective effects in ammonia toxicity.

Effects of omentectomy on the peritoneal fibrinolytic system.

PURPOSE: Decreased fibrinolytic activity in the serosal surfaces of peritoneal tissue appears to be a major factor in the development of peritoneal fibrous adhesions. The omentum reduces peritoneal adhesion by creating a mechanical barrier and producing fibrinolytic factors. This experimental study was designed to investigate the effects of omentectomy on the peritoneal fibrinolytic system. METHODS: Thirty animals were assigned randomly to a control group or an omentectomy group. On postoperative day 10, peritoneal and blood samples were collected and adhesions were graded qualitatively. We measured the concentrations of serum and peritoneal tissue plasminogen activator, peritoneal plasminogen activator inhibitor-1, tissue plasminogen activator/plasminogen activator inhibitor complex, and hydroxyproline. RESULTS: Adhesions were significantly increased after omentectomy. Omentectomy also resulted in a reduction of both serum and tissue "tissue plasminogen activator" levels. On the other hand, an increment in "plasminogen activator inhibitor-1" levels was observed after omentectomy. There were no differences in "tissue plasminogen activator/plasminogen activator inhibitor" complex or "hydroxyproline" levels. CONCLUSION: Omentectomy reduced peritoneal fibrinolytic activity significantly and the peritoneal plasminogen activator system showed corruption that did not resolve with the rest of the peritoneal system after omentectomy.

The protective effect of erythropoietin on renal injury induced by abdominal aortic-ischemia-reperfusion in rats.

BACKGROUND: Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The purpose of this study is to examine the effect of erythropoietin on renal injury induced by aortic IR in rats. MATERIAL AND METHODS: Twenty-four Wistar-Albino rats were randomized into 3 groups (8 per group). The control group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. The aortic IR group underwent clamping of the infrarenal abdominal aorta for 30 min followed by 60 min of reperfusion. The aortic IR + erythropoietin group underwent the same aortic IR periods and was pretreated with 1000 U/kg subcutaneous erythropoietin 5 min before ischemia. In rat kidney specimens, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase were measured. Histological evaluation of the rat kidney tissues was also done. RESULTS: Aortic IR significantly increased the levels of MDA and superoxide dismutase (P < 0.05 versus control). Erythropoietin significantly decreased the levels of MDA, superoxide dismutase, and catalase (P < 0.05 versus aortic IR). Histological evaluation showed that aortic IR significantly increased (P < 0.05 versus control), whereas erythropoietin significantly decreased (P < 0.05 versus aortic IR) the focal glomerular necrosis, dilation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, interstitial inflammatory infiltration, and congestion of blood vessels. CONCLUSIONS: The results indicate that erythropoietin has protective effects on renal injury induced by aortic IR in rats.

Influence of atropine therapy on fenthion-induced pancreatitis.

OBJECTIVE: We searched the influence of dose and timing of atropine therapy in fenthion-induced pancreatitis model. METHODS: All rats were intoxicated with fenthion except the control group. Two milligrams of atropine was administered for 24 hours in a high dose atropine group while a low dose atropine group received 100 micrograms of atropine for 24 hours. One group received 2 milligrams of atropine in the first four hours of intoxication while the other group received 2 milligrams of atropine in the last four hours before sacrifice. All rats were sacrificed 24 hours after intoxication. Pseudo-cholinesterase and lipase concentrations and histopathological markers of pancreatitis were studied. RESULTS: None of the models in this study completely prevented pancreatitis, however high dose atropine that is administered for 24 hours or the first four hours after intoxication prevented severe pancreatitis. CONCLUSION: Atropine administration influence on fenthion-induced pancreatitis should be studied for other organophosphates in animals and humans.

The effects of erdosteine on lung injury induced by the ischemia-reperfusion of the hind-limbs in rats.

BACKGROUND: [corrected] The goal of this experimental study was to investigate whether erdosteine has a protective effect against lung injury as a remote organ after hind-limb ischemia-reperfusion (I/R). MATERIALS AND METHODS: The rats were divided into three groups: control, I/R, and I/R + erdosteine. After the experimental procedure, nitric oxide (NO) levels, myeloperoxidase (MPO), adenosine deaminase (ADA), and the activities of xanthine oxidase (XO) were determined on the lung tissue. The levels of NO and activities of MPO were also measured on the bronchial alveolar lavage (BAL). In addition, the lung tissue was examined by histopathology. RESULTS: The lung tissue ADA and XO activities were increased in the I/R group compared with the control group (P < 0.05). In the I/R group, the levels of NO were higher than the control group (P < 0.05), whereas the erdosteine treatment did not alter the NO levels (P < 0.05). The MPO activities increased after I/R in the I/R group compared to both control and I/R + erdosteine group (P < 0.05). The activity of MPO increased in the IR group in comparison with the control group in BAL (P < 0.05). The activity of MPO in the I/R + erdosteine group was significantly lower than the I/R group in BAL (P < 0.05). NO levels increased in all I/R groups compared to control group in BAL (P < 0.05). However, treatment of erdosteine significantly decreased NO levels compared to I/R group (P < 0.05). The animals of the I/R group had total destruction of normal alveolar structure with the intense presence of infiltrating neutrophils and mononuclear phagocytes in histopathological examination. The rat lung exhibited mild degrees of destruction in the erdosteine group. CONCLUSIONS: As a result, erdosteine may be a protective effect for lung injury, decreasing oxidative stress and neutrophil accumulation after hind-limb I/R in rats.

Caffeic acid phenethyl ester reduces mortality and sepsis-induced lung injury in rats.

OBJECTIVE: Sepsis and ensuing multiorgan failure continue to be the major causes of mortality in intensive care units. Nuclear factor (NF)-kappaB activation is supposed to be one of the targets in the treatment of sepsis. We studied the effectiveness of caffeic phenethyl ester (CAPE), a known NF-kappaB inhibitor, in cecal ligation and puncture (CLP)-induced sepsis and lung injury. DESIGN: Randomized, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Female Sprague-Dawley rats. INTERVENTIONS: CLP was performed in all rats except the rats in control and sham+CAPE groups. CAPE was administered to rats at the time of operation in sham+CAPE and CAPE+sepsis 0 groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for assessment of interleukin-1, interleukin-6, interleukin-10, and tumor necrosis factor-alpha; the right lung was removed for histopathologic examination and the left lung for biochemical examination. Apoptosis, inducible nitric oxide synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were studied. The rest of the rats were observed for mortality. MEASUREMENTS AND MAIN RESULTS: Mortality was significantly decreased in groups that received CAPE compared with the sepsis group. All cytokine levels were similar to control levels only in the CAPE+sepsis12 group. Apoptosis, inducible nitric oxide synthase, and heat shock protein 70 evaluation were significantly changed between all groups in the following order: control < sham+CAPE< CAPE+sepsis12 < CAPE+sepsis 0 < sepsis. Malondialdehyde and catalase were increased in the sepsis group. CONCLUSIONS: CAPE reduced mortality in sepsis and improved histopathologic variables best when it was administered after the onset of sepsis.

Does the periodontal health of thalassemia major patients have an impact on the blood lipid profiles? A preliminary report.

Cardiac symptoms and premature death from cardiac causes are still suggested to be a major problem in thalassemic patients. One of the main reasons for the cardiovascular events in thalassemia major (TM) patients has suggested having iron overload, in addition to other reasons such as hypoxia, abnormal lipoproteins levels, atherosclerotic conditions, etc. This study aims to investigate whether the periodontal health has an impact on the blood lipid levels. Twenty-four TM patients and sex-matched controls (C) enrolled to this study. The measurements of the periodontal parameters (gingival index, plaque index, bleeding on probing, probing depth, and clinical attachment level) were recorded. Besides, in venous blood samples the lipid profile was investigated. All of the periodontal parameters were significantly higher in TM group than in C group (P<0.05). Triglyceride and cholesterol/high density lipoprotein ratio had significant positive correlations with the periodontal parameters (P<0.05). Multiple regression analyses present significant associations between gingival index, plaque index scores, and the cholesterol/high density lipoprotein ratio (P<0.001). Our study results showed that the lipid profile of TM patients might be affected by their periodontal health. Further studies are needed to determine the lipid profile involvement magnitude and the cardiovascular disease risk caused by the periodontal health of TM patients.

Protective effects of erdosteine and vitamins C and E combination on ischemia-reperfusion-induced lung oxidative stress and plasma copper and zinc levels in a rat hind limb model.

The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia-reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.

Influence of different atropine therapy strategies on fenthion-induced organ dysfunction in rats.

We studied the influence of dose and timing of atropine therapy on fenthion-induced organ dysfunction. Thirty-six rats were randomized into six groups. All rats in the five groups except the control group were intoxicated with fenthion. The high-dose atropine group received 2 mg/kg of atropine, whereas the low-dose group received 100 microg/kg of atropine every hour for 24 hr. One group received 2 mg/kg of atropine in the first 4 hr of intoxication while the other group received 2 mg/kg of atropine in the last 4 hr before killed, which for all rats was 24 hr after intoxication. Pseudocholinesterase and aspartate aminotransferase and alanine aminotransferase levels and histopathological markers of lung, brain and liver were studied. None of our atropine therapy strategies in this study totally prevented harm on the three organs. Although the high dose of atropine administered for 24 hr had the least harmful markers for lung, it also had the most harmful markers for brain and liver. We did not succeed in finding a unique therapy strategy in our models beneficial for all studied organs in fenthion intoxication in rats. Atropine administration strategy should be oriented for the most affected organ pathology in fenthion intoxication.

Effect of lisinopril on rat liver tissues in L-NAME induced hypertension model.

N(G)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) is a non-specific nitric oxide (NO) inhibitor and it has been used to eliminate the role of NO in many studies like animal models for hypertension. In this study, we aimed to investigate whether lisinopril treatment has any biochemical and/or histopathological effect on rat liver tissue in a L-NAME-induced hypertension model. Forty-eight 6-weeks-old male Spraque-Dawley rats were used in the study. The animals used in the study were randomly divided into four equal groups. To induce hypertension, L-NAME was added to drinking water at a concentration of 600 mg/l and each rat was given 75 mg/kg/day of L-NAME for 6 weeks. Tail cuff systolic blood pressure (SBP) was measured at first, third, and sixth weeks. There was a significant difference between the experiment groups and controls. In only lisinopril given and L-NAME plus lisinopril administered groups, each rat was given 10 mg/kg of lisinopril for 6 weeks. At the end of the study, the animals were sacrificed. Blood and tissue samples were collected for biochemical and histopathological analysis. It has been observed that mean NO level was significantly decreased in L-NAME given group (p<0.05). Mean ALT levels were significantly increased in lisinopril and L-NAME plus lisinopril given groups, when compared with the control group (p<0.05). AST levels were in normal range in all groups (p>0.05). Hepatocyte degeneration was prominent in lisinopril given group, whereas mononuclear cell infiltration was significant in L-NAME given groups. Although the beneficial effects in L-NAME-induced hypertension treatment, lisinopril can lead to some unexpected results like hepatocyte degeneration, serum enzyme level elevation, and slight mononuclear cell infiltration.