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Marked antinephritic action and less adverse effects of methylprednisolone suleptanate by intermittent administration
H Taniguchi1, T Nagamatsu, R Kojima
1Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Abstract:
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.
Insights
Intermittent administration (IA) of methylprednisolone suleptanate (MPS) offers superior nephritis treatment compared to daily dosing. IA preserves adrenal function and enhances MPS efficacy in treating anti-GBM nephritis in rats.
Area of Science:
- Nephrology
- Pharmacology
- Immunology
Background:
- Glucocorticoids are used for nephritis treatment.
- Optimal administration regimens require further investigation.
- Methylprednisolone suleptanate (MPS) is a glucocorticoid with potential therapeutic applications.
Purpose of the Study:
- To compare the antinephritic effects of intermittent administration (IA) versus daily administration (DA) of MPS.
- To evaluate the influence of IA and DA of MPS on adrenal function.
- To establish an optimal regimen for prolonged glucocorticoid treatment in nephritis.
Main Methods:
- Crescentic-type anti-GBM nephritic rats were used.
- MPS was administered via IA (3 days on, 3 days off) and DA over a 40-day period.
- Urinary protein, serum cholesterol, glomerular alterations, adrenal gland size, corticosterone levels, and inflammatory cell infiltration (ED-1(+) and TH-1(+) cells) were assessed.
Main Results:
- Both IA and DA of MPS reduced urinary protein, serum cholesterol, and glomerular damage.
- IA demonstrated a more potent effect than DA on these parameters.
- IA preserved adrenal gland size and corticosterone levels, unlike DA.
- MPS significantly suppressed inflammatory cell infiltration in nephritic glomeruli.
Conclusions:
- Intermittent administration (IA) is a superior regimen for MPS treatment of nephritis compared to daily administration (DA).
- IA of MPS effectively treats nephritis while mitigating adverse effects on adrenal function.
- MPS exerts its antinephritic action by inhibiting mesangial cell proliferation, monocyte/macrophage infiltration, and antibody production.