Effects of high doses of dexamethasone on hemodynamic and immunohistochemical characteristics of acute paraquat intoxication in rat kidneys.

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) (PQ), is a nonselective contact herbicide that is highly toxic to humans. The kidney is affected during PQ intoxication. Dexamethasone (Dexa) has anti-inflammatory effects and is used to treat cases of PQ poisoning. We investigated in rat kidney hemodynamic effects and immunohistochemical characteristics of Dexa treatment in acute PQ poisoning. Adult male rats were divided into four groups: 1, untreated control; 2, treated with 100 mg/kg Dexa; 3, treated with 25 mg/kg PQ; 4, treated with PQ + Dexa. Mean arterial pressure (MAP) and heart rate (HR) were recorded during the experimental period (2 h). Tissues were removed after 2 h and immunohistochemistry was performed after 24 h. Paraffin sections of kidney were prepared and anti-cyclo-oxygenase-1 (COX-1), anti-cyclo-oxygenase-2 (COX-2), anti-angiotensin converting enzyme (ACE), anti-aquaporin-1 (AQU-1), anti-vascular cell adhesion molecule (VCAM) primary antibodies were used for immunohistochemical examination. Immunoreactivities were scored as: (1) minimal, (2) weak, (3) mild, (4) moderate, (5) strong and (6) very strong. MAP and HR were measured at 10 min, 20 min, 1 h and 2 h. MAP at 10 and 20 min and 1 h was increased in the Dexa group. HR also was increased in all groups compared to controls at 2 h. Compared to groups 2 and 4, MAP values decreased significantly in group 3 at 1 h. The intensity of all of immunoreactivities was decreased in group 2. In group 3, immunoreactivities of COX-1, COX-2 and ACE were decreased compared to the control and the other groups, whereas AQU-1 and VCAM immunoreactivities were the same as the control group. ACE and VCAM immunoreactivities were decreased in group 4 compared to the control group, while COX-1, COX-2 and AQU-1 immunoreactivities were close to those of the control group. Dexa appears to be useful for treating PQ intoxication.

Effects of acute treatment with dexamethasone on hemodynamic and histopathological changes in rats.

We assessed the time-dependent effects of intraperitoneal (i.p.) and intravenous (i.v.) application of dexamethasone (Dexa) on the mean arterial blood pressure (MAP), heart rate (HR) and total blood volume (TBV). We evaluated also the relation between the effects and immunoreactivities of transforming growth factor-beta (TGF-ß), epithelial nitric oxide synthase (eNOS), interleukin-1 beta (IL1-ß) and vascular endothelial growth factor (VEGF) in rat brain, lung and kidney tissues. Rats were anesthetized and while still breathing spontaneously, a tracheotomy and femoral vein and artery catheterizations were performed. To determine TBV using the hemodilution method, 2 ml albumin-electrolyte solutions were applied by i.v. injection. Group 1 (control group) received a 1 ml bolus injection of physiologic saline, Group 2 received 15 mg/kg and Group 3 received 75 mg/kg Dexa i.p. The hematocrit was measured at 10, 20, 60 and 120 min. For each animal, the values of MAP, HR and TBV were measured within 2 h. For immunohistochemical evaluation, anti-TGF-ß, anti-eNOS, anti-IL1-ß and anti-VEGF primary antibodies were tested using the avidin-biotin-peroxidase method. TBV was decreased in Group 1 and the increase in MAP was statistically significant. HR values increased slightly. None of the values changed significantly in Group 2. Although TBV was unchanged in Group 3, the decrease in MAP was statistically significant. HR values increased, but the increase was not statistically significant. Mild IL1-ß immunoreactivity and moderate TGF-ß, eNOS and VEGF immunoreactivities were observed in the brain, lung and kidney samples in Group 1. Increased eNOS immunoreactivity in the kidney samples were observed in Group 2. eNOS immunoreactivity was as strong in the brain and the kidney samples in Group 3. Decreased VEGF immunoreactivity was observed in the lung and kidney tissues in Group 3. Significantly decreased TGF-ß immunoreactivity was observed in all tissue samples in Group 3. The decreased MAP values in Group 3 differed from those in Groups 1 and 2. Despite increased eNOS immunoreactivity, especially in brain and kidney, the decrease in VEGF immunoreactivity in Group 3, especially lung and kidney, were consistent with a drop in blood pressure.

Statin treatment reduces oxidative stress-associated apoptosis of sciatic nerve in diabetes mellitus.

Statins are lipid-lowering drugs that are widely used for treating hyperlipidemia, especially in diabetic patients. The aim of our study was to explore the effects of atorvastatin on oxidative stress and apoptosis in the sciatic nerve due to hyperglycemia. Diabetes was induced by streptozotocin. Atorvastatin was given orally for two weeks beginning from the sixth week. Microscopic examination of sciatic nerve revealed that normal tissue organization was disrupted in streptozotocin induced diabetic rats. Treatment with Atorvastatin reduced the histological damage and protected the morphological integrity of the sciatic nerve in streptozotocin induced diabetes. Increased expressions of transforming growth factor beta-1, endothelial nitric oxide synthase and TUNEL in sciatic nerve from streptozotocin induced diabetes were reduced by Atorvastatin. Atorvastatin could improve the effects of oxidative stress and apoptosis on the sciatic nerve due to diabetes.

The effects of DBcAMP on the expression of eNOS, iNOS and TGF-beta in rat heart tissue.

Dibutryl (DB) adenosine 3',5'-cyclic monophosphate (cAMP) is an important modulator of physiological functions. To determine the protective effects of DBcAMP on heart tissue, we evaluated changes in immunoreactivity of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta (TGF-beta) in left cervical vagotomized rats treated with DBcAMP. Male rats were divided into four groups. In Group 1, animals were subjected to a left cervical vagotomy. Group 2 received a 1 ml bolus injection of 15 ml/kg DBcAMP in addition to the left vagotomy. DBcAMP alone was given to Group 3 and Group 4 was the control group. For each animal, mean arterial pressure (MAP) and heart rate (HR) were measured. For indirect immunohistochemistry, anti-eNOS, anti-iNOS, and anti-TGF-beta primary antibodies were used. In Group 1, MAP and HR values decreased slightly. In Groups 2 and 3, DBcAMP induced a statistically significant drop in HR and MAP. In Group 1, strong eNOS, iNOS, and TGF-beta immunoreactivities were observed. Immunostaining intensities decreased in Groups 2 and 3. The results of the study reported here suggest that increased immunoreactivities of eNOS, iNOS, and TGF-beta might contribute to the effects on the heart tissue after left vagotomy and imply that DBcAMP acts on heart tissue via nitric oxide.

Testosterone and nonverbal intelligence in right-handed men with successful and unsuccessful educational levels.

The relationship between serum total testosterone (T) concentration and fluid intelligence (nonverbal, spatial) was studied in consistently right-handed men with successful (S) or unsuccessful educational levels (NS). Hand preference was assessed by the Edinburgh Handedness Inventory. Nonverbal intelligence was measured by Cattell's Culture Fair Intelligence Test. Serum T level was determined using chemiluminescence enzyme-immunoassay on hormone autoanalyzer. There was no significant difference between the mean T levels of the S subjects and NS subjects, although S-men tended to have higher T levels than NS-men. The mean IQ was found to be significantly higher in S-men than NS-men. In the total sample (S + NS men), the correlation between T to IQ was best described by a polynomial regression (3rd order), exhibiting an inverse U-shaped regression. In S-men, the relationship between T and IQ was best described by a polynomial regression equation of the 3rd order; however, the relationship was not U-shaped, but rather a positive correlation (low T: low IQ and high T high IQ). In NS-men, there was an inverse U-shaped correlation between T and IQ (low and very high T: low IQ and moderate T: high IQ). The present data suggest that (i) very low and very high serum T concentrations may be disadvantageous, (ii) moderate T levels may be advantageous for general fluid intelligence, and (iii) a prewired cerebral organization may be essential for the T effects on cognitive abilities.