In order to elucidate the mechanisms of the antinephritic action of
TJ-8014, the effect of this
drug on
corticosterone release from the adrenal cortex was investigated by using normal rats and rats with original-type
anti-GBM nephritis. When the serum
corticosterone level was determined 5 hr after test drugs were given p.o. to normal rats,
TJ-8014 at 0.5 and 2.0 g/kg significantly elevated the
hormone level by 48% and 74%, respectively. Of the crude drugs that constitute
TJ-8014, Bupleuri radix (SAIKO) and Glycyrrhizae radix (KANZOU) at 1.0 g/kg also significantly elevated the serum level. When
TJ-8014 was given p.o. daily from the next day of
anti-GBM serum injection to the 15th day, 2.0 g/kg/day of the
drug inhibited the urinary
protein excretion. In addition,
TJ-8014 (2.0 g/kg/day) inhibited the decrease in the serum and adrenal
corticosterone levels induced by
nephritis. When
corticosterone at 10 mg/kg was given s.c. daily from the next day of the anti-serum injection to the 10th day, it not only reduced
proteinuria, but also inhibited glomerular histopathological changes. In contrast,
metyrapone, a
corticosterone synthetase inhibitor, at 100 mg/kg x 2/day, p.o., aggravated the
nephritis. These results suggest that the antinephritic action of
TJ-8014 may be partly due to the enhancement of the synthesis or release of
corticosterone from the adrenal cortex.