Elenara Rieger

INTRAPERITONEAL GLYCEROL INDUCES OXIDATIVE STRESS IN RAT KIDNEY

1 Glycerol has been used for the treatment of intracranial hypertension, cerebral oedema and glaucoma. Experimentally, intramuscular administration of hypertonic glycerol solution is used to produce acute renal failure. In this model, glycerol causes rhabdomyolysis and myoglobinuria, resulting in the development of renal injury. The pathogenesis is thought to involve vascular congestion, the formation of casts and oxidative stress. However, the effect of glycerol itself independent of rhabdomyolysis has not been investigated. Therefore, the aim of the present study was to investigate the effects of i.p. glycerol on some biochemical and oxidative stress parameters in the kidney of young rats. 2 Rats received 10 mL/kg, i.p., hypertonic glycerol solution (50% v/v) or saline (NaCl 0.85 g%) followed by 24 h water deprivation. Twenty‐four hours after the administration of glycerol, rats were killed. Creatinine levels and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in the plasma. In addition, CK, pyruvate kinase and LDH activity and oxidative stress parameters (free radical formation, lipid peroxidation and protein carbonylation) were measured in renal tissue. 3 Glycerol did not alter plasma CK activity and increased plasma creatinine levels, suggesting renal insufficiency and the absence of rhabdomyolysis. Renal CK and pyruvate kinase activity was decreased, suggesting diminution of energy homeostasis in the kidney. Plasma and renal LDH activity was decreased, whereas the formation of free radicals, lipid peroxidation and protein carbonylation were increased, suggesting oxidative stress. 4 These results are similar to those described after the intramuscular administration of glycerol. Therefore, it is possible that glycerol may provoke renal lesions by mechanisms other than those induced by rhabdomyolysis.

Neuroprotective Effect of Creatine and Pyruvate on Enzyme Activities of Phosphoryl Transfer Network and Oxidative Stress Alterations Caused by Leucine Administration in Wistar Rats

Maple syrup urine disease is an autosomal metabolic disease caused by a deficiency of branched-chain α-keto acid dehydrogenase complex activity. In this disease occur the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and their corresponding branched-chain α-keto acids in the tissues and body fluids. The affected patients may present psychomotor development delay and mental retardation. The pathophysiology of maple syrup urine disease is not entirely understood, but leucine seems to be the primary neurotoxic metabolite. Creatine and pyruvate are energetics and antioxidants substances. In this study, we investigated the effects of leucine administration and co-administration of creatine plus pyruvate on several parameters of oxidative stress and phosphoryl transfer network in cerebral cortex and hippocampus of Wistar rats treated from the 8th to the 21st postpartum day. Leucine induced oxidative stress and diminished the activities of pyruvate kinase, adenylate kinase, cytosolic and mitochondrial creatine kinase. Co-administration of creatine plus pyruvate prevented the alterations provoked by leucine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that chronic administration of leucine may stimulate oxidative stress and alters the enzymes of phosphoryltransfer network in the cerebral cortex and hippocampus of the rats. It is possible that these effects may contribute, along with other mechanisms, to the neurological dysfunction found in patients affected by maple syrup urine disease. In this case, it is possible that creatine plus pyruvate supplementation could benefit to the patients.