Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine, and its mechanisms (2): Effect on the release of corticosterone from adrenal glands.
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.
Hattori
T
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Nagamatsu
T
T
Ito
M
M
Suzuki
Y
Y
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004365:Drugs, Chinese Herbal; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009393:Nephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004364:Pharmaceutical Preparations; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000032:analysis*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D004365:Drugs, Chinese Herbal; D004364:Pharmaceutical Preparations; D010936:Plant Extracts; C061187:sho-saiko-to-kyo-shokyo-ka-oren-bukuryo; D003345:Corticosterone; D008797:Metyrapone