Animal models interstitial fibrosis

In the Wistar rat model, the daily administration of 10 mg per kg body weight of AA induced, after 35 days, renal failure wifh interstitial fibrosis (Figure 2) as well as a papillary urothehal cardnoma of the pelvis in some animals [63,64]. Nephrotoxidty of different components of AA was also studied in three strains of inbred male mice. The C3H/He mice intraperitoneaUy injected with 2.5 mg/Kg of AA, five days a week, for 2 weeks, developed on day 14 foci of proximal tubule injury surrounded by mononuclear cell infiltration. Two weeks later, signs of proximal tubule cell prohf-eration were observed whereas the inflammatory ceUs infiltration became more severe and interstitial fibrosis occurred [65]. In this mice model, AAI exhibited a higher nephrotoxidty than AAII [65], which was also confirmed in in vitro studies on proximal tubular LLC-PKl ceUs line [66]. 

Nephrotoxicity associated with doxorubicin use is also dose dependent and occurs at the same time as doxorubicin-induced cardiotoxicity. Studies in animal models reveal glomerular effects, renal interstitial fibrosis, and vacuolization of tubules. However, clinical evidence of nephrotoxicity in the absence of cardiotoxicity is limited suggesting that dose reduction... 

The immunosuppressive drug cyclosporine A (CSA) has revolutionized transplant medicine. However, CSA induced-nephrotoxicity still represents a major therapeutic challenge. Chronic CSA nephropathy is characterized by a decrease in glomerular filtration rate (GFR), tubular atrophy, interstitial fibrosis and progressive renal dysfunction. It is difficult to delineate the mechanisms of CSA toxicity from clinical data since the majority of clinical experiences with CSA have been in renal transplant recipients. Animal models of CSA nephropathy have brought some insights, how-... 

Studies also have shown direct effects of aldosterone on the heart and vascular lining aldosterone induces hypertension and interstitial cardiac fibrosis in animal models. The increased cardiac fibrosis is proposed to result from direct mineralocorticoid actions in the heart rather than from the effect of hypertension, because treatment with spironolactone, a MR antagonist, blocks the fibrosis without altering blood pressure. Similar effects of mineralocorticoids on cardiac fibrosis in human beings may explain, at least in part, the beneficial effects of spironolactone in patients with congestive heart failure (see Chapter 33). 

Hartenbower DL, Coburn JW (1972) A model of renal insufficiency in the chick. Lab Anim Sci 22 258-261 Ishidoya S, Morrissey J, McCracken R et al. (1995) An-giotensinll receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney Intern 47 1285-1294 Klahr S, Morrissey JJ (1997) Comparative study of ACE inhibitors and angiotensinll receptor antagonists in interstitial scarring. Kidney Intern 52, Suppl 63 111-114 Sancho JJ, Duh Qy, Oms L et al. (1989) A new experimental model for secondary hyperparathyroidism. Surgery 106 1002-1008... 

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