Experimental studies on multiorgan toxicity of cyclosporine-A in rats using a radiopharmaceutical and comparison with histopathological findings.
Iodine-125 HIPDM was evaluated as a screening agent for studying multiorgan toxicity due to Cyclosporine-A (CsA) and the results were compared to histopathological findings of the tissues. The rats were injected subcutaneously with 50 mg/kg (body weight) of CsA or with equal volume of the vehicle, Cremophor-EL, for 7 consecutive days. A dose of 10 microCi of I-125 HIPDM was injected intravenously at the end of the treatment period. The results indicated that there was a significant increase in the uptake of I-125 HIPDM in the kidney, liver, heart and blood compared to control rats (P < 0.05). However, there was a significant decrease in the uptake of I-125 HIPDM in the spleen compared to control animals (P < 0.001). The lung and brain of CsA treated rats showed no change in the uptake of I-125 HIPDM when compared to control rats. The change in the uptake of I-125 HIPDM in these organs was assumed to indicate tissue response to the toxic effects of CsA. The radiopharmaceutical results were comparable with the histopathological findings in which the organs showed varying degrees of tissue degeneration. It is concluded that the lipophilic radiopharmaceutical, I-125 HIPDM, can be used as an effective screening agent to study multiorgan toxicity due to CsA.
Shihab-Eldeen
A
A
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Owunwanne
A
A
Junaid
T A
TA
Yacoub
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects* / Q000473:pathology*; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; D007462:Iodobenzenes; D016572:Cyclosporine; C036739:N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine