Renal and macrophage aminopeptidase activities in cyclosporin-treated mice.
Cyclosporin, an immunosuppressive drug, is known to affect macrophage and to exert a nephrotoxic effect. Aminopeptidases play important roles for renal and macrophage functions. In this work, we attempt to test the hypothesis that the aminopeptidases participate within macrophage and renal effects induced by cyclosporin. Macrophage and renal aminopeptidase activities of cyclosporin-treated and control mice were evaluated, as well as renal caspase 3 activity, hematocrit, urinary protein and plasma osmolality, creatinine and uric acid concentrations. Cyclosporin treatment increased caspase 3 activity, hematocrit and osmolality, while urinary protein, creatinine and uric acid were unaltered. Soluble and particulate aminopeptidases in resident and elicited macrophages were unaffected by cyclosporin. The treatment with cyclosporin increased neutral, basic, cystyl, prolyl imino and pyroglutamyl soluble aminopeptidase activities in the renal cortex. Acid and basic soluble aminopeptidase activities increased in the renal medulla. Increased levels of particulate form in the cortex were detected for acid and pyroglutamyl aminopeptidase activities. Cyclosporin increased cortical soluble while decreased medullar particulate prolyl dipeptidyl aminopeptidase IV activity. With the exception of prolyl dipeptidyl aminopeptidase IV, particulate aminopeptidase activities returned to levels similar to controls after fifteen days of cyclosporin withdrawal, and soluble aminopeptidase activities did not regress. Our data indicate that the adopted regimen of cyclosporin treatment produced mild renal impairment with consistent changes on the levels of renal but not macrophage aminopeptidase activities. The obtained profiles of macrophage and renal aminopeptidase activities should be considered into the elaboration of new potential strategies for preventing nephrotoxicity during the treatment with cyclosporin.
Marinho
Camila Eduardo
CE
Laboratory of Pharmacology, Instituto Butantan, 05503-900, São Paulo, Brazil.
Olivo
Renata do Amaral
Rdo A
Zambotti-Villela
Leonardo
L
Ribeiro-de-Andrade
Tabatha Novikov
TN
Fernandes
Cristina Maria
CM
Silveira
Paulo Flavio
PF
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000652:urine; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D000626:Aminopeptidases