Investigation of the effects of ethanol and taurine, singly and in combination, on metabolic, functional and proinflammatory changes in the kidney of diabetic rats

A chemically-induced rat model of diabetes has been used to elucidate the role of low to moderate ethanol (EtOH) consumption and of taurine (TAU) in diabetes-induced renal metabolic, functional, proinflammatory and proapoptotic changes relevant to the development of diabetic complications. For this purpose, EtOH and TAU were provided singly or in combination using a pretreatment or a posttreatment approach. In pretreatment experiments, male Sprague-Dawley rats drank EtOH (5% or 15%, v/v) in place of water from days 1 to 28 and received the diabetogen streptozotocin (STZ, 60 mg/kg, i.p.) on day 15. In posttreatment experiments, rats received STZ on day 1, drank water from days 1 to 14, and received EtOH (5% or 15%, v/v) in place of drinking water from days 15 to 28. TAU (2.4 mM/kg) was given by oral gavage following the EtOH schedule, by itself or along with EtOH. Nondiabetic rats receiving only water or only EtOH, TAU or EtOH-TAU, and untreated diabetic rats served as controls. Body weight gains and food, fluid and EtOH consumptions were monitored periodicallly. Blood, kidney and a 24 hr urine sample were collected on day 29 from all the rats and used for chemical and biochemical-testing. Untreated diabetic rats consumed more food, fluid and EtOH, and gained less body weight than their nondiabetic counterparts. In addition they exhibited frank hyperglycemia, hyperphagia, polydipsia, glucosuria and proteinuria and, relative to control rats, showed higher levels of plasma proinflammatory cytokines and fatty acids and a higher plasma creatinine/urea ratio, voided more urine, and excreted more electrolytes in the urine. In the kidney, diabetes increased the activity of key enzymes of glycolysis, gluconeogenesis, pentose phosphate pathway, and sorbitol pathway as well as of malate dehydrogenase and glyoxalase-I; but lowered that of citrate synthase, malic enzyme, p-hydroxybutyrate dehydrogenase and ATP citrate lyase. In addition, there was an increased renal accumulation of cholesterol, triglycerides, glucose and glycogen, increases in proinflammatory cytokine levels and in caspase-3 activity, and a lower ATP/ADP ratio. Without exceptions, EtOH, TAU and EtOH-TAU afforded various degrees of protection against diabetes-induced systemic and renal changes. Moreover, in the case of Et01-1. the extent of the effects was found to depend on both the timing of the consumption and the concentration of its solution. Generally, 15% EtOH was more effective than either 5% EtOH or TAU in attenuating the changes in urinary volume, urinary excretion of electrolytes, plasma creatinine/urea ratio, urinary creatinine and urea excretion, accumulation of renal glucose and- lipids, activities of malic enzyme and of enzymes of glycolysis, gluconeogenesis and pentose phosphate pathway, and the secretion of proinflammatory cytokines -in the plasma and kidney. On the other hand, 5% EtOI-I was more effective than 15% in influencing the renal activities of malate dehydrogenase, citrate synthase, glyoxalase-I and caspase-3, the renal ATP/ADP ratio, and the levels of circulating free fatty acids. With only a few isolated instances, a pretreatment approach with EtOH, TAU or EtOH-TAU was more effective than a posttreatment one in lowering diabetes-induced alterations. Except for its greater protective effects against changes in renal glucose, glycogen and lipids levels, TAU was usually intermediate in potency to 5% and 15% EtOH or weaker. Furthermore, regardless of the concentration of EtOH consumed, a co-treatment with TAU almost always led to a greater protective action than with either treatment agent alone. In conclusion, the intake of a low to moderate amount of EtOH can provide a high degree of protection against diabetes-induced renal changes with potential for fostering complications when consumed before or after the onset of diabetes. In both instances, the supplementation of EtOH with TAU can lead to a greater renal protection then is possible with either treatment agent alone, possibly as a result of independent mechanisms of action.