thiotaurine and Disease-Models--Animal

In this study, the actions of taurine (TAU), a sulfonate, and thiotaurine (TTAU), a thiosulfonate, on diabetes-mediated biochemical alterations in red blood cells (RBCs) and plasma and on the RBC membrane, morphology and spectrin distribution were examined in rats. Diabetes was induced in male Sprague-Dawley rats with streptozotocin (60 mg/kg i.p.) and allowed to progress for 14 days. From days to 56, the rats received a daily, 2.4 mmol/kg, oral dose of TAU or TTAU, 2 mL oral dose of physiological saline or 4 U/kg subcutaneous dose of isophane insulin (INS). Naive rats served as the control group. The rats were sacrificed on day 57 and their blood was collected to measure HbA(1c), to isolate intact RBCs, and to obtain plasma. A 6-weeks treatment with INS effectively lowered the elevations in plasma glucose, cholesterol, triglycerides, and plasma and RBC malondialdehyde and glutathione disulfide while effectively counteracting the decreases in plasma INS, plasma and RBC glutathione redox status, and plasma and RBC activities of antioxidant enzymes caused by diabetes. Also, INS returned the echynocytic appearance and peripheral location of spectrin seen in RBCs from diabetic rats to the normal discocytic shape and uniform distribution. TAU and TTAU were as effective as INS in inhibiting malondialdehyde formation, changes in redox status and oxidative stress in both the plasma and RBC, but were much less effective in controlling hyperglycemia and hypoinsulinemia. Furthermore TTAU was more effective than INS or TAU in lowering the increase in cholesterol to phospholipids ratio in the RBC membrane and, unlike TAU, it was able to normalize the RBC morphology and spectrin distribution.

Topics: Animals; Antioxidants; Blood Glucose; Catalase; Cell Shape; Cholesterol; Diabetes Mellitus, Experimental; Disease Models, Animal; Erythrocytes; Glutathione Disulfide; Glutathione Peroxidase; Glycated Hemoglobin; Insulin; Lipid Peroxidation; Male; Phospholipids; Protective Agents; Rats; Rats, Sprague-Dawley; Spectrin; Superoxide Dismutase; Taurine; Triglycerides

This study has compared the actions of the sulfur-containing compounds taurine (TAU) and thiotaurine (TTAU) with those of insulin (INS) on the oxidative stress that develops in the aorta and heart as a result of diabetes. Diabetes was induced in male Sprague-Dawley rats with streptozotocin (60 mg/kg, i.p.). Starting on day 15, and continuing for the next 41 days, the diabetic rats received each day 2 mL of physiological saline or 2.4 mmol/kg/2 mL of TAU (or TTAU) p.o. or 4 U/kg of isophane INS s.c. Normal rats served as controls. The rats were sacrificed on day 57 to collect blood, heart and thoracic aorta samples. Untreated diabetic rats exhibited a lower body weight gain (by 34%), higher than normal plasma glucose (by ∼4-fold), cholesterol (by 66%) and triglycerides (by 188%) levels, and lower INS levels (by 76%). Also there was a marked increase in catalase activity (≥90%); and clear decreases in nitrite (≥40%), glutathione redox status (≥67%), and glutathione peroxidase (≥66%) and superoxide dismutase (≥51%) activities in both the aorta and heart. With only a few isolated instances (plasma lipids), TTAU was either markedly more effective (plasma glucose, plasma INS, aorta and heart glutathione, aorta redox status, and antioxidant enzymes) or marginally more effective (heart redox status) than TAU in attenuating the alterations brought about by diabetes. These results suggest that replacing the sulfonic acid group of TAU by thiosulfonic acid can lead to a greater potency against diabetes-related biochemical changes in the plasma, heart and aorta. However, except for effects on plasma lipids, these sulfur-containing compounds were less effective than INS in counteracting diabetes-related changes.

Topics: Animals; Aorta; Blood Glucose; Catalase; Cholesterol; Diabetes Mellitus, Experimental; Disease Models, Animal; Glutathione Disulfide; Glutathione Peroxidase; Insulin; Male; Malondialdehyde; Myocardium; Nitric Oxide; Nitrites; Organ Size; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Taurine; Triglycerides; Weight Gain

Taking into account the proven effectiveness of antioxidants in preventing experimentally induced diabetes in laboratory animals, this study was carried out with the specific purpose of comparing the effectiveness of two known antioxidants, the β-aminosulfonate taurine (TAU) and β-aminothiosulfonate thiotaurine (TTAU), in preventing biochemical, functional and histological alterations indicative of -diabetic nephropathy. In the study, streptozotocin (60 mg/kg, orally) was used to induce type 2 diabetes mellitus in Sprague-Dawley rats. Starting on day 15 and continuing up to day 56, the rats received a daily single 2.4 mmol/kg oral dose of a sulfur-containing compound (TAU or TTAU) or 4 U/kg subcutaneous dose of isophane insulin (INS). Rats not receiving any treatment served as controls. After obtaining a 24 h urine sample, the animals were sacrificed by decapitation on day 57, and their blood and kidneys immediately collected. Diabetic rats exhibited marked hyperglycemia, hypoinsulinemia, hypoproteinemia, hyponatremia, hyperkalemia, azotemia, hypercreatinemia, increased plasma TGF β(1), lipid peroxidation, plasma and kidney nitrite, and urine output; decreased glutathione redox status in plasma and kidney, decreased urine Na(+) and K(+), proteinuria and hypocreatinuria. Without exceptions, all the treatment compounds were found to markedly and variously attenuate these changes. Confirmation of protection by INS, TAU and TTAU was provided by the results of histological examination of kidney sections and which showed a more normal appearance than sections from diabetic animals. In most instances protection by TTAU was about equal to that by INS but greater than that by TAU.

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Creatinine; Diabetic Nephropathies; Disease Models, Animal; Glutathione Disulfide; Glycated Hemoglobin; Insulin; Kidney; Male; Malondialdehyde; Nitric Oxide; Protective Agents; Rats; Rats, Sprague-Dawley; Taurine; Transforming Growth Factor beta1; Weight Gain