The localisation of TPPS4 in some organs and its possible nephrotoxicity in rats.
Photodynamic therapy (PDT) is now being used more frequently in carefully selected cases of malignancies. The drugs used for PDT are mostly derivatives of haematoporphyrine (HPD) and its active component photofrine II. Another compound prepared by total synthesis is meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4) but its application in human medicine was rejected because of its neurotoxicity. Our TPPS4 was prepared by the method of Busby et al. in the modification of Jirsa and Kakac (1987). This product is purer and without neurotoxic effects. In this study, we concentrated our attention on the effect of TPPS4 on nephrotoxicity and its accumulation in some organs. As the parameters of toxic kidney damage we used urine levels of N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine levels, glomerular filtration rate (GFR) and proteinuria. TPPS4 was administered i.v. in a dose of 25 mg/kg b.w. The animals were observed for 21 days after drug application. Urine and blood samples were collected over 24-hour periods on days 0, 5 and 21. The serum creatinine level was significantly higher only on day 5 (65.0+/-1.46 micromol/l vs 56.5+/-2.69 micromol/l on day 0, p<0.05). There were no significant changes in GFR, proteinuria or NAG activity in the urine during the experiment. AST serum activity was increased. We determined the concentration of TPPS4 (pmol/mg w.w.) in rat organs on the 21st day after the injection. The concentration of TPPS4 was high in kidneys (30.8+/-5.5), liver (13.5+/-2.0), lungs (11.7+/-4.6) and spleen (9.7+/-1.5), while the concentration in heart and brain was low. We conclude that TPPS4 has the highest concentration in the kidney 21 days after its administration and does not exert any nephrotoxic effects during this period.
Zima
T
T
First Institute of Medical Chemistry and Biochemistry, Charles University, Prague, Czech Republic.
Jirsa
M
M
Jirsa
M
M
Bradová
V
V
Stejskal
J
J
Zabka
J
J
Povýsil
C
C
Janebová
M
M
D000818:Animals; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate