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Investigations concerwing the prenatal-toxicological effects of humic acid on rats
AI6
1140-1200 Hall I
Toxicology 81
I~IWE~T~G . . . . .
~-S ~O.,~P~.II, G TH3 P~!EZTXT~%I-TOXICO~OG!C~:Z E ~ E C T S
OP Hb-MIC AOID ON RATS S I E G P R I E D GOLBS, H ~ N P R E D I ~ T ,
V O ~
IaUOHS, O A I ~ O S P O L O
~l-Marx-Universit> of L e i p z i g / G D R , Inst. ~ e t . - P h a r m a c o l o g y , Z w i c k a u e r S t r a f e 55, G D R - 7 0 1 0 L e i p z i g Prenatal-toxicological examinations, which include both embryot o x i c o l o g i c a l and t e r a t o l o g i c a l s t u d i e s , c o u l d be c a r r i e d out in a d i r e c t e x p e r i m e n t on the rats. The i n v e s t i g a t i o n of the s e n s i t i v i t y of these l a b o r a t o r y r a t s to p r e n a t a l - t o x i c o l o g i c a l e x p e r i m e n t s c o u l d be a c c o m p l i s h e d by u s i n g p o s i t i v e c o n t r o l g r o u p s ( a d m i n i s t r a t i o n for e x a m p l e of cyclophosphan~ide or t r y p a n b l u e ) . The f o l l o w i n g e s s e n t i a l p a r a m e t e r s i n d i c a t e d the p r e n a t a l - t o x i c o l o g i c a l e f f e c t s : n u m b e r of the f e r t i l i t y d i s p o s i t i o n , n ~ m b e r of the l i v i n g and d e a d f o e t u s e s per a n i m a l c a p a b l e of b r e e d i n g , b o d y - w e i g h t of the f o e t u s e s , r a t e of r e t a r d a t i o n etc. ~ c o r d i n g to the r e s u l t s of the i n v e s t i g a t i o n s on r a t s (h~nic acid) c o u l d be f o u n d that h u m i c acids h a v e not p r e n a t a l - t o x i c o l o g i c a l e f f e c t s after a d m i n i s t r a t i o n (oral or ip.).
1200-1220 Hall I
IN VIVO : IN VITRO CORRELATIONS OF THE EFFECT OF GENTAMICIN ON THE RELEASE OF ENZYMES FROM THE RAT RENAL TUBULE Suresh B. Chahwala and Ernest S. Harpur Pharmacology Laboratories, Department of Pharmacy, University of Aston, Gosta Green, Birmingham B4 7ET, U.K. The amlnoglycoslde a n t i b i o t i c s (AAs), e.g. gentamicln, are Known to be nephrotoxlc causing a primary lesion in the proximal tubules, Urinary levels
of enzymes such as the lysosomal hydrolases acid phosphatasa (AP) and N-acetyl-B-glucosamlnidasa (NAG) may be a sensitive index of such damage. Autoradlographlc studies have shown that gentamlcln accumulates in the iysosomes of proximai tubule ceils and in vitro incubation of AAs wlth isolated rat kidney lysosomes promotes the release of free lysosomal hydrolasas. We have studied the effect of gentamicin on the release of AP and NAG from freshly isolated rat renal tubules. In vitro incubation of tubules in the presence of gentamlcin resulted in a pattern of enzyme release which was a function of the time of incubation and both the gentamlcin and protein concentration. Isolated renal tubules also have been prepared from kidneys of rats which had been injected with gentamlcln [40 mg/kg/day) for i, 3 or 5 days (water-injected controls). Rats were housed individually in metabolism cages with free access to food and water. Twenty-four hour urines ware collected continuously for two days prior to commencing injections and throughout the injection period. Urinary levels of NAG ware elevated after one dose (i15~ of control) and continued to rise when the drug was given for 5 days (300~ of control). Animals were killed 24 hours after the last injection. After 30 mln incubation of the renal tubule preparation the release of NAG was 273~ of the control level following a single injection, increased to 329~ after 3 injections and returned towards the control after 5 injections (178~). The pattern of release of lactate dehydrogenase (a cytosolic enzyme) was similar to NAG both in vivo and in vitro.
1140-1200 Hall I
Toxicology 81
I~IWE~T~G . . . . .
~-S ~O.,~P~.II, G TH3 P~!EZTXT~%I-TOXICO~OG!C~:Z E ~ E C T S
OP Hb-MIC AOID ON RATS S I E G P R I E D GOLBS, H ~ N P R E D I ~ T ,
V O ~
IaUOHS, O A I ~ O S P O L O
~l-Marx-Universit> of L e i p z i g / G D R , Inst. ~ e t . - P h a r m a c o l o g y , Z w i c k a u e r S t r a f e 55, G D R - 7 0 1 0 L e i p z i g Prenatal-toxicological examinations, which include both embryot o x i c o l o g i c a l and t e r a t o l o g i c a l s t u d i e s , c o u l d be c a r r i e d out in a d i r e c t e x p e r i m e n t on the rats. The i n v e s t i g a t i o n of the s e n s i t i v i t y of these l a b o r a t o r y r a t s to p r e n a t a l - t o x i c o l o g i c a l e x p e r i m e n t s c o u l d be a c c o m p l i s h e d by u s i n g p o s i t i v e c o n t r o l g r o u p s ( a d m i n i s t r a t i o n for e x a m p l e of cyclophosphan~ide or t r y p a n b l u e ) . The f o l l o w i n g e s s e n t i a l p a r a m e t e r s i n d i c a t e d the p r e n a t a l - t o x i c o l o g i c a l e f f e c t s : n u m b e r of the f e r t i l i t y d i s p o s i t i o n , n ~ m b e r of the l i v i n g and d e a d f o e t u s e s per a n i m a l c a p a b l e of b r e e d i n g , b o d y - w e i g h t of the f o e t u s e s , r a t e of r e t a r d a t i o n etc. ~ c o r d i n g to the r e s u l t s of the i n v e s t i g a t i o n s on r a t s (h~nic acid) c o u l d be f o u n d that h u m i c acids h a v e not p r e n a t a l - t o x i c o l o g i c a l e f f e c t s after a d m i n i s t r a t i o n (oral or ip.).
1200-1220 Hall I
IN VIVO : IN VITRO CORRELATIONS OF THE EFFECT OF GENTAMICIN ON THE RELEASE OF ENZYMES FROM THE RAT RENAL TUBULE Suresh B. Chahwala and Ernest S. Harpur Pharmacology Laboratories, Department of Pharmacy, University of Aston, Gosta Green, Birmingham B4 7ET, U.K. The amlnoglycoslde a n t i b i o t i c s (AAs), e.g. gentamicln, are Known to be nephrotoxlc causing a primary lesion in the proximal tubules, Urinary levels
of enzymes such as the lysosomal hydrolases acid phosphatasa (AP) and N-acetyl-B-glucosamlnidasa (NAG) may be a sensitive index of such damage. Autoradlographlc studies have shown that gentamlcln accumulates in the iysosomes of proximai tubule ceils and in vitro incubation of AAs wlth isolated rat kidney lysosomes promotes the release of free lysosomal hydrolasas. We have studied the effect of gentamicin on the release of AP and NAG from freshly isolated rat renal tubules. In vitro incubation of tubules in the presence of gentamlcin resulted in a pattern of enzyme release which was a function of the time of incubation and both the gentamlcin and protein concentration. Isolated renal tubules also have been prepared from kidneys of rats which had been injected with gentamlcln [40 mg/kg/day) for i, 3 or 5 days (water-injected controls). Rats were housed individually in metabolism cages with free access to food and water. Twenty-four hour urines ware collected continuously for two days prior to commencing injections and throughout the injection period. Urinary levels of NAG ware elevated after one dose (i15~ of control) and continued to rise when the drug was given for 5 days (300~ of control). Animals were killed 24 hours after the last injection. After 30 mln incubation of the renal tubule preparation the release of NAG was 273~ of the control level following a single injection, increased to 329~ after 3 injections and returned towards the control after 5 injections (178~). The pattern of release of lactate dehydrogenase (a cytosolic enzyme) was similar to NAG both in vivo and in vitro.