Reflection on the choice of a model to show the protective effect of high dilutions in mercury and cisplatin-induced nephritis in rats

Author(s): Redon, P., Castaing, N. , Dorfman, P. , Cambar, J.

Journal/Book: Proc GIRI. 1989; 3: 119-121.

Abstract: Many studies have already reported the in vitro and in vivo effect of high dilutions of metals on animal or vegetal organisms. Some of these studies have even shown that the toxicity induced by material doses of certain metals caii be greatly decreased by a preventive or a curative treatment with very high dilutions of the same or similar metals. We have reported a protective effect of high dilutions of mercury and cisplatin in heavy metal induced nephritis assessed by mice mortality. More recently, we have tried to show a similar protective effect of cisplatin high dilutions in cisplatin nephritis in rats; the protective effect was assessed by measuring tubular enzyme excretion every day over the 15-days experimental period. On the basis of the elimination kinetics of these enzymes, it was not possible to clearly establish a protective effect of these high dilutions; in some experiments, we even noted increased renal toxicity with some dilutions. Moreover, very recently, in an in vitro model in cell lines from renal proximal tubular portions (LLCPK1), cell viability kinetics was assessed with different cisplatin concentrations (10-2 to 10-11 M) used alone with high cisplatin dilutions (4,5,7,or 9C) or by pretreating the cells for 24 h with the dilutions and then exposing them to toxic doses for 24 h. The pretreatment did not lead to protection if cytotoxicity was assessed immediatly after 24h of intoxication; this pretreatment seemed partly protective if cytotoxicity was assessed 24h after culture medium was changed. In conclusion, it seems clear that the choice of the experimental model, namely mortality rate in mice, renal damage severity in rats or cytotoxicity in renal cultures, determines the significance of the protective effect of very high dilutions of metal- induced nephrotocicity.

Keyword(s): hom. br. meth. anim. mercurius. intox. nephritis.

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