Experimental Models of Renal Failure

When behavioral recordings are coupled with electroencephalography, in a digital format, the so-called Video-EEG, allows to prove, in freely moving animals, the behavioral and EEG effects after star fruit ingestion or after local apphcation in specific brain regions of either, the crude or the purified toxin. In the first case the hypothesis that experimentally uremic animals, induced by HgCl, a known model of renal failure [48], will reproduce the star fruit intoxication effects found in the patients can be tested (see above). In the second case, the hypothesis that the crude or purified toxin per se will be able to induce behavioral and EEG activity compatible with brain hyperexcitability, possibly associated to seizures is tested. As a positive effect, the latter experimental protocol (with not relationships with renal alterations) will even validate the potential of this neurotoxin as a new tool in the neuroscience field. 

Lieberthal W, Nigam SK. Acute renal failure. II. Experimental models of acute renal failure imperfect but indispensable. Am J Physiol Ren Physiol 2000 278 Fl-12. 

Stein JH, Fried TA Experimental models of nephrotoxic acute renal failure. Transplant.Proc. 17 72-80,1985... 

There is some experimental data, which could explain why some patients in the long-term may experience such unfavourable effects of ACEI. In a Fisher to Lewis rat model of chronic renal transplant failure treatment with either an ACEI or an angiotensin 11 receptor antagonist prevented the development of proteinuria and glomerulosclerosis, but not of interstitial damage. Moreover both these agents enhanced the development of intimal hyperplasia and reduced renal function [95]. This data was further corroborated when the same group showed that ACEI both in healthy rats... 

The mechanisms of the changes in cell viability during renal injury are incompletely understood. Most of the experimental data have been derived from the ischemia-reperfusion model of acute renal failure and have focused on necrotic cell death. Because as many as 50% of patients have ischemia-induced acute renal failure, the observations should be relevant to a large portion of the patients at risk. Also, different stresses initiate common biochemical events, so that understanding the relevant pathways of one stress will most likely be applicable to others. What follows is a detailed analysis of some of the pathways currently thought to execute cell death in a variety of nephrotoxic insults. 

---