[Effects of Realgar and prescription containing Realgar on stress response proteins, inflammatory mediators and complements in fever rat models].
OBJECTIVE
To explore the pharmacological mechanism of Realgar by the way of studying the effects of Realgar and the prescription containing Realgar named Niuhuang Jiedu Tablet on stress response proteins (heat shock protein 70, HSP70 and heme oxygenase-1, HO-1), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha), activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS), and complements C3, CA under pathologic status (fever model).


METHODS
SD rats were randomly divided into four groups, 15 rats in each: untreated normal group, fever model group, Realgar (90 mg/kg) group and Niuhuang Jiedu Tablet (NJT, 1.404 g/kg) group. Each group was divided into three subgroups (5 rats/subgroup). Blood samples of the rats in subgroups were collected at 1 h, 2 h and 4 h after administration, respectively. ELISA method was used to determine HSP70, IL-1beta, IL-6, and TNF-alpha levels in serum. Dual wavelength spectrophotometry was used to determine activity of HO-1 in serum. Spectrophotometry was used to test activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS) in serum. Immunonephelometery method was used to test complements C3, C4 in serum.


RESULTS
Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group. The increase ranges of HO-1 activities at different time post administration changed with the arsenic concentration in rat serum. Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. NJT significantly inhibited activities of NOS and iNOS in rat serum as compared with the fever model group at 2 h after administration.


CONCLUSIONS
Realgar as contained in certain prescriptions, at certain specific levels, assists in removal of internal toxins by inducing stress protein (HSP70, HO-1) to improve the positive stress level in the body and inhibiting some over-releasing inflammatory mediators (IL-1beta) to reduce the inflammatory reactions under pathologic status.
Tang
Yi-shan
YS
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. tangyishan2005@yahoo.com.cn
Wang
Ning-sheng
NS
Zhang
Yin-qing
YQ
Ye
Shao-mei
SM
Ou
Wei-ping
WP
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005334:Fever / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D051547:Heme Oxygenase-1 / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D019001:Nitric Oxide Synthase / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*; D013997:Time Factors
D001152:Arsenicals; D003176:Complement C3; D003181:Complement C4; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D013440:Sulfides; C058317:arsenic disulfide; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1