Marked antinephritic action and less adverse effects of methylprednisolone suleptanate by intermittent administration in rats.
To establish the regimen for beneficial prolonged treatment with glucocorticoids on nephritis, we investigated the antinephritic effect of methylprednisolone suleptanate (MPS) and its influence on adrenal function by intermittent administration (IA) in comparison with daily administration (DA) in crescentic-type anti-GBM nephritic rats. In IA, MPS (0.25, 1.0 and 3.0 mg/kg) was injected for 3 successive days followed by a 3-day withdrawal during a 40-day period. MPS inhibited the elevation of urinary protein and serum cholesterol and glomerular alterations by both IA and DA. The effect of MPS on these parameters was more potent by IA than by DA. MPS significantly suppressed the increment of the number of ED-1(+) cells and TH-1(+) cells in nephritic glomeruli. DA, but not IA, caused atrophy of the adrenal glands. IA prevented the remarkable decrease in corticosterone level provoked in nephritic rats. In conclusion, for the treatment of nephritis, IA seems to be a better regimen for the administration of MPS. MPS may exert an antinephritic action by inhibiting mesangial cell proliferation and infiltration of monocytes/macrophages into glomeruli in addition inhibiting antibody production.
Taniguchi
H
H
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Nagamatsu
T
T
Kojima
R
R
Ito
M
M
Suzuki
Y
Y
D000311:Adrenal Glands / Q000033:anatomy & histology; D000818:Animals; D000906:Antibodies / Q000097:blood; D001485:Basement Membrane / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D002784:Cholesterol; D003404:Creatinine; C052305:methylprednisolone suleptanate; D003345:Corticosterone; D008775:Methylprednisolone