A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or Rhizoma Ligustici extract on the comparative toxicokinetics of strychnine and brucine in rats.
Recently, the renal injury caused by Semen strychni and its major toxic constituents, strychnine and brucine, was reported in many clinical cases. Hence, this study was conducted to investigate the renal injury induced by Semen Strychni and the protective effects of Radix Glycyrrhizae and Rhizoma Ligustici. The protective mechanisms were related to the comparative toxicokinetics of strychnine and brucine. Serum and urine uric acid and creatinine were used as renal function markers to evaluate the condition of kidney, and renal injury was directly reflected by histopathological changes. Compared with rats in blank group and protective herb groups, rats in Semen Strychni high-dose group showed significant differences in the results of renal function markers, and various glomerular and tubular degenerations were found in the histopathological study. The decreased AUC (only strychnine) and Cmax, the increased Tmax by Radix Glycyrrhizae and the decreased T1/2 by Radix Glycyrrhizae and Rhizoma Ligustici were found in model groups. Results indicated that high dose of Semen Strychni might induce renal injury. Radix Glycyrrhizae and Rhizoma Ligustici might work together and have effects on the elimination of strychnine and brucine. The protective effects of Radix Glycyrrhizae might also be explained by the slow absorption of the alkaloids.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Liqiang
L
Gu
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Xiaofan
X
Wang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Zhenzhen
Z
Liu
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Ping
P
Ju
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Lunhui
L
Zhang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Yuanyuan
Y
Zhang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bingjie
B
Ma
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Kaishun
K
Bi
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: cxh_syphu@hotmail.com.
Xiaohui
X
Chen
D000818:Animals; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D041743:Herb-Drug Interactions; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000652:urine; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry*; D013331:Strychnine / Q000009:adverse effects / Q000031:analogs & derivatives*; D031451:Strychnos / Q000009:adverse effects; D066007:Toxicokinetics; D014527:Uric Acid / Q000652:urine
D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D014527:Uric Acid; C083806:brucine; D003404:Creatinine; D013331:Strychnine
Brucine; Herb–herb interaction; Kidney injury; Semen Strychni; Strychnine; Toxicokinetic