Peter Wingenfeld

The Mechanisms of Taurine Mediated Protection against Cell Damage Induced by Hypoxia and Reoxygenation

Taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency and reoxygenation. Different mechanisms are responsible for the improved survival of the renal cell cultures. Taurine markedly reduces the osmoregulatory deterioration during hypoxia and reoxygenation. Calcium homeostasis was markedly improved. Ca2+ efflux during hypoxia as well as Ca2+ overload during reoxygenation was significantly reduced by the amino acid. The effect of taurine was partly comparable to the effect induced by Ca2+ channel blockers. One of the effects mainly responsible for cellular protection seems to be the taurine-induced acceleration of cellular growth processes in spite of hypoxia and reoxygenation. The spectrum of cytoprotective effects of taurine predisposes this substance to be a physiological protective agent responsible for cellular homeostasis or enantiostasis.

Taurine Reduces Experimental Liver Injury after Cold Ischemic Preservation and a Period of Rewarming Prior to Reperfusion

Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringers solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringers solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).

Acute glaucoma and intracranial hypertension in a child on long-term peritoneal dialysis treated with growth hormone

A 7-year-old boy with end-stage renal disease on long-term peritoneal dialysis is described. The child developed intracranial hypertension and acute glaucoma during therapy with recombinant human growth hormone (rhGH), 18 months after the onset of treatment. Symptoms developed within 1.5 days and required neurosurgical treatment to reduce the intracranial hypertension because of imminent impaction of the cerebellum and brain stem. After ventricular cerebrospinal fluid drainage and cessation of growth hormone, all symptoms of intracranial hypertension and increased intraocular pressure disappeared. To our knowledge this is the first report of intracranial hypertension or hydrocephalusand acute glaucoma during rhGH therapy. Continuous and long-term control of the ophthalmological and neurological status of patients treated with rhGh is indicated.

Influence of Taurine Supplementation on Ischemic Preservation of the Isolated Rat Kidney

Taurine (2-aminoethanesulfonic acid) is an endogenous amino acid with unique functions as a modulator of transmembraneous calcium transport, an osmoregulator and putatively a free radical scavenger4,7,12.

Protecting effect of Taurine against Hypoxic Cell Damage in Renal Tubular Cells Cultured in Different Transplant Preservation Solutions

We conclude that, within this experimental model and under these experimental conditions, taurine supplementation of standard kidney preservation solutions improves survival of kidney cells during hypoxic preservation. The protective effect depends on the taurine concentration, the hypoxic preservation time and the used preservation solution. Physiological taurine concentrations are effective during short hypoxic periods, whereas pharmacological taurine concentrations seem to be needed for longer periods of hypoxia. Within this experimental model University of Wisconsin solution seems to be more effective than Euro collins solution.

Energetic status and viability of porcine kidney cells after hypoxic, hypothermic preservation in UW solution and subsequent reoxygenation: the influence of taurine

Abstract Taurine (2-aminoethane sulfonic acid) is a physiologic compound with osmoregulative properties and presumbly an inhibitor of lipid peroxidation. The present study evaluates the effects on the viability of isolated kidney cells of the addition of various doses of taurine to the UW preservation solution. Porcine tubular cell monolayers were incubated at 4°C for 9 h in UW solution under hypoxic conditions, and subsequently reoxygenated for 30 min in Hanks balanced salt solution equilibrated with room air. Taurine was added to the preservation solution at final concentrations of 0, 1, 10 ot 20 mmol/1. Cel viability was assessed by exclusion on Trypan blue and by determination of the energetic status reoxygenation. While tuarine had no influence on the post-hypoxic vaibility according to Trypan blue exclusion, a dose-related increases in cellular content of high energy phosphates after post-hypoxic reoxygenation was observed after addition of taurine to the preservation medium. It is concluded that taurine is able to reduce tissue alterations during hypoxia and reoxygenation and that the determination of post-hypoxic recovery of energy metabolism may be a more sensitive indicator of cell viability than the morphological Trypan blue exclusion test.

Protective Effect of Taurine on Hypoxia and Reoxygenation-Induced Damage of Human Colon Cells (HT 29)

In this experimental model, taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency, and the beneficial effect outlasted the period of reoxygenation. The mechanisms for the improved survival rates are postulated to be a reduced osmoregulatory disturbance of cellular integrity, improved Ca2+ homeostasis and induction of accelerated cellular growth processes. In our simplified cell culture model the UW solution seems to be the most appropriate solution for the cold (hypoxic) preservation of human colon cells. We conclude, that within this experimental model and under these experimental conditions, taurine supplementation of the conventionally used preservation solutions improved the solutions markedly. Considering our previous studies, taurine seems to be a potent endogenous protective agent against cellular deterioration due to hypoxia and reoxygenation.

Effect of pressure-controlled reperfusion on postischemic recovery of the normal and the normotensive-hypertrophied heart

Abstract The influence of pressure-controlled reperfusion on the postischemic outcome of normal and normotensive hypertrophied rat hearts should be investigated. To induce normotensive cardiac hypertrophy, male Wistar rats received injections of isoprenaline (5 mg/kg s.c. bid for three days). Hearts were excised and perfused using the Langendorff technique at a perfusion pressure of 75 mmHg for 30 min. After cardioplegia and 40 min of global ischemia at 25°C the hearts were reperfused for 45 min. Reperfusion pressure was built up either abruply (75 mmHg immediately) or gradually (from 40 mmHg to 75 mmHg within 30 min). Postischemic recovery was significantly affected by the mode of reperfusion in normal hearts where pressure-controlled (gradual) reperfusion is superior to the abrupt reperfusion mode. In hypertrophied hearts the postischemic outcome did not differ from normal hearts if abrupt reperfusion was used, but gradual reperfusion only led to a comparably small amelioration of postischemic status. It is concluded that cardiac hypertrophy, in our model, does not alter the ischemic tolerance of the heart under abrupt reperfusion, but results in a reduced susceptibility to the benefits of the gradual reperfusion mode.