- Email: [email protected]
Effect of cannabis on transport mechanism through liver cell membrames
A26 1220-1240 Hall 1
Toxicology 81
EFFECT OF CARMABIS ON TRANSPORT ~ECHANI$~! THROUGH LIVER CELL ~IE~IBRA~IES ReDetto, M., Sanz, P., ~odrinuez-Vicente, C. I n s t i t u t o Nacional de T o x i c o l o p i a . ~ e v i l l a . A . P . 863. Spain. In nrevious assays about the influence of cannabis on d i f f e r e n t biochemical parameters, ~e observed, with hiph doses, a clear decrease of i n t r a c e l l u l a r ~lycogen, ~thilst the amount of 91ucose in serum and l i v e r extracts ~as not a f f e c t e d ; a s l i g h t i n h i b i t i o n of t o t a l ATP-ase was also observed in r a t l i v e r extracts. These same results have been confirmed in rats subjected to d i f f e r e n t i n t e n s i t y and duration treatments, as ~.!ell as a considerable i n h i b i t i o n of G-6-Pase in the membrane f r a c t i o n from l i ver homogenates, which increases ~.tith time. A d i r e c t interference bet~een cannabis and the transport mechanism of 91ucose throuoh c e l l u l a r membranes is then suggested.
POSTER SESSIOM I (4-5 March 1981) I-I IMPROVED TOXIOI~ OF INTRAVENOUS 5-'DEOXY-5-FLUOROURIDIIiE (5'-DFUR) IN COMPA~ IS I ON WITH 5-FLUOROURACIL IN RATS. TE~LI~IN, DVN, w i t h the a s s i s t a n c e of B r i g i t t e Roos B i o l o g i c a l P h a r m a c e u t i c a l Research Department F. Hoffn~nn-La Roche & Co., L t d . , CH-4002 Basle, S w i t z e r l a n d 5 - f l u o r o u r a c i l , an a n t i m e t a b o l i t e of p y r i m i d i n e b a s e s , i s widely used f o r the t r e a t m e n t of GI-, l i v e r - , p a n c r e a s - and . ~ - . . ~ y t u ~ o u r s . The t h e r a p y i s l i m i t e d by 5-FU's inhibiting effect on haematopoesis (Stalest et al., 1965) and its atrophic effect on the colonic mucosa. 5'-Deoxy-5-fluorouridine (5'-DFUR) is a new derivative of 5-FU. 18 rats/sex/group received both compounds intravenously f o r 5 weeks i n doses of 10 and 20 ~ / ~ / d a y f o r 5-FU and 50, 150 and 300 ~/~/dal for 5'-DFUR. i0 mg/kg/day of 5-FU administered in the first 2 weeks of the study were well tolerated; 20 m~/kg/day caused immediate body weight loss, deterioration of general condition, alopecia, diarrhoea, anaemia, leucocytopenia, thrombocytopenia and death in most of the rats. Bone marrow e-aminations showed markedly reduced cellularity and megaloblastic cell-line changes. In contrast 50, 150 and 300 mg/kg/day of 5'-DFUR were generally well tolerated. Haematologically only mild to moderate reductions of red and white blood counts were noted in the rats fed the highest dose; pronounced anaemia and leucocytopenia were only seen in 2 "highdose" rats. Histologically the bone marrows showed enly minor degrees of depletion. Both compounds showed comparable anti-tumour activities in experimental models (N~artmann and Bollag, 1980) based on the specific effect of 5-FU. 5'-DFUR is converted to 5-FU by the enzyme uridinephosphorylaee. Tumour cells contain higher uridinephosphorylase concentrations than normal cells resulting in an enrichment of 5-FU in these cells. 5'-DFUR can therefore be considered a pro-drug of 5-FU with distinctly reduced toxicity. References: H.R. Hartmann, W. Bollag: Schweiz. reed. Wschr. IiO, 1078, 19CO. R.C. Stalzer, J.M. Kiely, G.L. Pease, A.L. Brown: Cancer 18, 1071, 196~.
Toxicology 81
EFFECT OF CARMABIS ON TRANSPORT ~ECHANI$~! THROUGH LIVER CELL ~IE~IBRA~IES ReDetto, M., Sanz, P., ~odrinuez-Vicente, C. I n s t i t u t o Nacional de T o x i c o l o p i a . ~ e v i l l a . A . P . 863. Spain. In nrevious assays about the influence of cannabis on d i f f e r e n t biochemical parameters, ~e observed, with hiph doses, a clear decrease of i n t r a c e l l u l a r ~lycogen, ~thilst the amount of 91ucose in serum and l i v e r extracts ~as not a f f e c t e d ; a s l i g h t i n h i b i t i o n of t o t a l ATP-ase was also observed in r a t l i v e r extracts. These same results have been confirmed in rats subjected to d i f f e r e n t i n t e n s i t y and duration treatments, as ~.!ell as a considerable i n h i b i t i o n of G-6-Pase in the membrane f r a c t i o n from l i ver homogenates, which increases ~.tith time. A d i r e c t interference bet~een cannabis and the transport mechanism of 91ucose throuoh c e l l u l a r membranes is then suggested.
POSTER SESSIOM I (4-5 March 1981) I-I IMPROVED TOXIOI~ OF INTRAVENOUS 5-'DEOXY-5-FLUOROURIDIIiE (5'-DFUR) IN COMPA~ IS I ON WITH 5-FLUOROURACIL IN RATS. TE~LI~IN, DVN, w i t h the a s s i s t a n c e of B r i g i t t e Roos B i o l o g i c a l P h a r m a c e u t i c a l Research Department F. Hoffn~nn-La Roche & Co., L t d . , CH-4002 Basle, S w i t z e r l a n d 5 - f l u o r o u r a c i l , an a n t i m e t a b o l i t e of p y r i m i d i n e b a s e s , i s widely used f o r the t r e a t m e n t of GI-, l i v e r - , p a n c r e a s - and . ~ - . . ~ y t u ~ o u r s . The t h e r a p y i s l i m i t e d by 5-FU's inhibiting effect on haematopoesis (Stalest et al., 1965) and its atrophic effect on the colonic mucosa. 5'-Deoxy-5-fluorouridine (5'-DFUR) is a new derivative of 5-FU. 18 rats/sex/group received both compounds intravenously f o r 5 weeks i n doses of 10 and 20 ~ / ~ / d a y f o r 5-FU and 50, 150 and 300 ~/~/dal for 5'-DFUR. i0 mg/kg/day of 5-FU administered in the first 2 weeks of the study were well tolerated; 20 m~/kg/day caused immediate body weight loss, deterioration of general condition, alopecia, diarrhoea, anaemia, leucocytopenia, thrombocytopenia and death in most of the rats. Bone marrow e-aminations showed markedly reduced cellularity and megaloblastic cell-line changes. In contrast 50, 150 and 300 mg/kg/day of 5'-DFUR were generally well tolerated. Haematologically only mild to moderate reductions of red and white blood counts were noted in the rats fed the highest dose; pronounced anaemia and leucocytopenia were only seen in 2 "highdose" rats. Histologically the bone marrows showed enly minor degrees of depletion. Both compounds showed comparable anti-tumour activities in experimental models (N~artmann and Bollag, 1980) based on the specific effect of 5-FU. 5'-DFUR is converted to 5-FU by the enzyme uridinephosphorylaee. Tumour cells contain higher uridinephosphorylase concentrations than normal cells resulting in an enrichment of 5-FU in these cells. 5'-DFUR can therefore be considered a pro-drug of 5-FU with distinctly reduced toxicity. References: H.R. Hartmann, W. Bollag: Schweiz. reed. Wschr. IiO, 1078, 19CO. R.C. Stalzer, J.M. Kiely, G.L. Pease, A.L. Brown: Cancer 18, 1071, 196~.