ABSTRACT
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.
Subject(s)
Dexamethasone/pharmacology , Hemodynamics/drug effects , Kidney Cortex/drug effects , Paraquat/toxicity , Animals , Anti-Inflammatory Agents/pharmacology , Dose-Response Relationship, Drug , Immunohistochemistry , Male , RatsABSTRACT
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.
Subject(s)
Apoptosis/drug effects , Diabetes Mellitus, Experimental/complications , Diabetic Neuropathies/drug therapy , Heptanoic Acids/pharmacology , Oxidative Stress/drug effects , Pyrroles/pharmacology , Sciatic Nerve/drug effects , Animals , Atorvastatin , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Diabetic Neuropathies/metabolism , Diabetic Neuropathies/pathology , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Nitric Oxide Synthase/drug effects , Nitric Oxide Synthase/metabolism , Pyrroles/therapeutic use , Rats , Rats, Wistar , Sciatic Nerve/pathology , Streptozocin , Transforming Growth Factor beta1/drug effects , Transforming Growth Factor beta1/metabolismABSTRACT
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.
