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Li B.-Q.,Shandong University | Li N.,Shandong Hongli Laboratory Animal Experiment Co. | Wang S.-J.,A Think Pharmaceutical Co. | Gao J.-Y.,Shandong Hongli Laboratory Animal Experiment Co. | Fang S.-H.,Shandong Hongli Laboratory Animal Experiment Co.
National Journal of Physiology, Pharmacy and Pharmacology | Year: 2012

Aims: Oridonin is a new anti-tumor drug candidate with promising broad spectrum antitumor activity. The aim of the present study is to investigate the single- and repeated-dose pharmacokinetics of injectable beta-cyclodextrin-oridonin inclusion complexin rats. Materials and methods: Rats were given single- or multiple-dose (7 days) of injectable beta-cyclodextrin-oridonin inclusion complex (single-dose: 33 mg/m2, 99 mg/m2, 296 mg/m2; repeatede-dose: 99 mg/m2 calculated as oridonin) by intravenous injection. Plasma Oridonin was analyzed by LC-ESI-MS. The main pharmacokinetics parameters were calculated and compared. Results: The PK data of single-dose injectable beta-cyclodextrin-oridonin inclusion complex in rats were best fit by a three-compartment model.The terminal elimination half-life (t1/2z) of oridonin ranged from 8.72±1.14 to 10.87±2.03h. AUC (0-t) and Cmax for oridonin showed statistically significant differences (p < 0.05) between singledose and repeated dose. Conclusion: Our study has led to the view that injectable beta-cyclodextrin-oridonin inclusion complex can increase the bioavailability of oridonin in rats and is suitable for once a day dosing. However, caution should be taken with when injectable beta-cyclodextrin-oridonin inclusion complex is given by i.v. repeatedly.


Li B.-Q.,Shandong University | Dong X.,Shandong Hongli Laboratory Animal Experiment Co. | Fang S.-H.,Shandong Hongli Laboratory Animal Experiment Co. | Yang G.-Q.,Shandong Hongli Laboratory Animal Experiment Co. | And 4 more authors.
Journal of Toxicological Sciences | Year: 2010

Aim: Non-cell corynebacterium parvum product (NCPP) is a new preparation of coryne-bacterium parvum (CP), an immunomodulator that displays anticancer activities. It is prepared by nanotechnology and is intended to minimize the side effects of CP. The aim of the present study was to evaluate the immunogenicity and systemic toxicity of NCPP compared with CP in animals. Methods: 30 monkeys were randomly divided into 5 groups and given CP (3 mg/monkey), three doses of NCPP (9, 3, 1 mg/monkey) and 0.9% normal saline (NS, 4 ml/monkey) individually by intramuscular injection twice a week for 13 weeks. The immunogenicity and systemic toxicity of NCPP and CP were compared. Results: NCCP and CP caused histopathological changes in the liver, spleen and kidney, but pathologic changes in NCCP-treated groups were slighter than that in the CP group. Only 9 mg/monkey of NCPP caused the similar damage as the CP in intensity. Deposition of immune complexes in the glomerular basement membrane was observed only in the CP group. ELISA detection showed that the anti-CP antibody was at a high level, while the anti-NCPP antibody was at low level and disappeared during the recovery period. Conclusion: Our study has led to the view that NCPP is safer than CP.


Li B.-Q.,Shandong University | Dong X.,Shandong Hongli Laboratory Animal Experiment Co. | Fang S.-H.,Shandong Hongli Laboratory Animal Experiment Co. | Gao J.-Y.,Shandong Hongli Laboratory Animal Experiment Co. | And 2 more authors.
Drug and Chemical Toxicology | Year: 2011

Polyethylene glycol 400 (PEG-400) has been used in injections. However, limited data are available concerning the toxicity of a high dose of PEG-400 following intravenous (i.v.) injection. The aim of the present study was to estimate the systemic toxicity and toxicokinetics of a high dose of PEG-400 in dogs following i.v. injection. Twenty-four dogs were divided into four groups: a control group receiving normal saline and three test groups receiving 4.23, 6.34, and 8.45 g/kg of PEG-400, respectively, by i.v. injection once a day for 30 days. The repeated-dose toxicity of PEG-400 was assessed. Toxicokinetic parameters of PEG-400 in dogs were estimated on days 1 and 30. Dry mouth and dry nasal mucus membrane were observed in dogs treated with 6.34 and 8.45 g/kg of PEG-400. Cloudy swelling of kidney cell and increased glomerular volume were observed in dogs treated with 8.45 g/kg of PEG-400 when the animals were sacrificed 24 hours after the last injection. No significant histological changes were found 21 days later. Repeated dosing did not affect the toxicokinetic profile of PEG-400 in dogs. This study has shown that the toxicity of a high dose of PEG-400 following repeated intravenous injections is low, and alterations produced are reversible. © 2011 Informa Healthcare USA, Inc.


Li B.-Q.,Shandong University | Fang S.-H.,Shandong Hongli Laboratory Animal Experiment Co. | Dong X.,Shandong Hongli Laboratory Animal Experiment Co. | Li N.,Shandong Hongli Laboratory Animal Experiment Co. | And 5 more authors.
European Journal of Drug Metabolism and Pharmacokinetics | Year: 2013

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel superoxide dismutase mimic. It exhibits strong free-radical scavenging activities in vitro and in vivo. The aim of the present study was to investigate the pharmacokinetics, tissue distribution and excretion of HSJ-0017 in Wistar rats following a single intravenous administration. Wistar rats were given different doses of HSJ-0017 by single intravenous injection. Biological samples of rats were collected and were assayed by the HPLC method. The pharmacokinetics, tissue distribution and excretion of HSJ-0017 were investigated. The pharmacokinetic data of HSJ-0017 in rats following intravenous injection was best-fit by a two-compartment model. T max of HSJ-0017 in plasma following intravenous injection was 0.083 h. AUC and plasma drug concentration were found to increase in a dose-related fashion. The highest concentrations of HSJ-0017 were detected in the liver (82.25 ± 13.99 μg/g) of rats, followed by the kidney, small intestine, lung, plasma, heart, spleen, and stomach within 2 h postdose. No HSJ-0017 was detected in the uterus, parorchis or brain of rats during the 24-h period of examination. The total cumulative excretion of HSJ-0017 in rat bile and urine were found to be 78.85 and 67.58 %, respectively. Our study has led to the view that the HSJ-0017 can be rapidly distributed to tissues after intravenous administration, but cannot diffuse through the blood-brain barrier. The faecal and biliary excretion of unchanged HSJ-0017 are the major routes of HSJ-0017 elimination. © 2013 Springer-Verlag France.


Li B.-Q.,Shandong University | Dong X.,Shandong Hongli Laboratory Animal Experiment Co. | Li N.,Shandong Hongli Laboratory Animal Experiment Co. | Gao J.-Y.,Shandong Hongli Laboratory Animal Experiment Co. | And 5 more authors.
Experimental Biology and Medicine | Year: 2014

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamineinduced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001– 10 μmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 μmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ- 0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic. © 2014 by the Society for Experimental Biology and Medicine.

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