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Evaluation of hepatotoxicity potential of a potent traditional Tibetan medicine Zuotai.
Journal of Ethnopharmacology
Short Title: Journal of Ethnopharmacology
Format: Journal Article
Publication Date: 2019/04/24/
Pages: 112 - 118
Sources ID: 93436
Notes: Accession Number: 134863620; Zhou, Liang-Liang 1,2,3 Chen, Hai-Juan 2,4 He, Qiang-Qiang 2 Li, Cen 2 Wei, Li-Xin 2,4 Shang, Jing 1,2,3; Email Address: shangjing21cn@cpu.edu.cn; Affiliation:  1: School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China  2: Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, University of the Chinese Academy of Sciences, Xining 810008, China  3: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China  4: University of Chinese Academy of Sciences, Beijing 100049, China; Source Info: Apr2019, Vol. 234, p112; Subject Term: HEPATOTOXICOLOGY; Subject Term: DIAGNOSIS; Subject Term: LIVER; Subject Term: ANATOMY; Subject Term: ANIMAL experimentation; Subject Term: APOPTOSIS; Subject Term: FISHES; Subject Term: GENE expression; Subject Term: LIVER cells; Subject Term: TIBETAN medicine; Subject Term: MERCURY; Subject Term: MESSENGER RNA; Subject Term: POLYMERASE chain reaction; Subject Term: STAINS & staining (Microscopy); Subject Term: WESTERN immunoblotting; Subject Term: PLANT extracts; Subject Term: CASPASES; Subject Term: CELL viability; Subject Term: CYTOCHROME P-450; Author-Supplied Keyword: Hepatocytes; Author-Supplied Keyword: Hepatotoxicity; Author-Supplied Keyword: HgS; Author-Supplied Keyword: Zebrafish; Author-Supplied Keyword: Zuotai; NAICS/Industry Codes: 416210 Metal service centres; NAICS/Industry Codes: 212299 All Other Metal Ore Mining; Number of Pages: 7p; Document Type: Article; Full Text Word Count: 5608Accession Number: 134863620; Zhou, Liang-Liang 1,2,3 Chen, Hai-Juan 2,4 He, Qiang-Qiang 2 Li, Cen 2 Wei, Li-Xin 2,4 Shang, Jing 1,2,3; Email Address: shangjing21cn@cpu.edu.cn; Affiliation:  1: School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China  2: Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, University of the Chinese Academy of Sciences, Xining 810008, China  3: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China  4: University of Chinese Academy of Sciences, Beijing 100049, China; Source Info: Apr2019, Vol. 234, p112; Subject Term: HEPATOTOXICOLOGY; Subject Term: DIAGNOSIS; Subject Term: LIVER; Subject Term: ANATOMY; Subject Term: ANIMAL experimentation; Subject Term: APOPTOSIS; Subject Term: FISHES; Subject Term: GENE expression; Subject Term: LIVER cells; Subject Term: TIBETAN medicine; Subject Term: MERCURY; Subject Term: MESSENGER RNA; Subject Term: POLYMERASE chain reaction; Subject Term: STAINS & staining (Microscopy); Subject Term: WESTERN immunoblotting; Subject Term: PLANT extracts; Subject Term: CASPASES; Subject Term: CELL viability; Subject Term: CYTOCHROME P-450; Author-Supplied Keyword: Hepatocytes; Author-Supplied Keyword: Hepatotoxicity; Author-Supplied Keyword: HgS; Author-Supplied Keyword: Zebrafish; Author-Supplied Keyword: Zuotai; NAICS/Industry Codes: 416210 Metal service centres; NAICS/Industry Codes: 212299 All Other Metal Ore Mining; Number of Pages: 7p; Document Type: Article; Full Text Word Count: 5608Accession Number: 134863620; Zhou, Liang-Liang 1,2,3 Chen, Hai-Juan 2,4 He, Qiang-Qiang 2 Li, Cen 2 Wei, Li-Xin 2,4 Shang, Jing 1,2,3; Email Address: shangjing21cn@cpu.edu.cn; Affiliation:  1: School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China  2: Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, University of the Chinese Academy of Sciences, Xining 810008, China  3: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China  4: University of Chinese Academy of Sciences, Beijing 100049, China; Source Info: Apr2019, Vol. 234, p112; Subject Term: HEPATOTOXICOLOGY; Subject Term: DIAGNOSIS; Subject Term: LIVER; Subject Term: ANATOMY; Subject Term: ANIMAL experimentation; Subject Term: APOPTOSIS; Subject Term: FISHES; Subject Term: GENE expression; Subject Term: LIVER cells; Subject Term: TIBETAN medicine; Subject Term: MERCURY; Subject Term: MESSENGER RNA; Subject Term: POLYMERASE chain reaction; Subject Term: STAINS & staining (Microscopy); Subject Term: WESTERN immunoblotting; Subject Term: PLANT extracts; Subject Term: CASPASES; Subject Term: CELL viability; Subject Term: CYTOCHROME P-450; Author-Supplied Keyword: Hepatocytes; Author-Supplied Keyword: Hepatotoxicity; Author-Supplied Keyword: HgS; Author-Supplied Keyword: Zebrafish; Author-Supplied Keyword: Zuotai; NAICS/Industry Codes: 416210 Metal service centres; NAICS/Industry Codes: 212299 All Other Metal Ore Mining; Number of Pages: 7p; Document Type: Article; Full Text Word Count: 5608Accession Number: 134863620; Zhou, Liang-Liang 1,2,3 Chen, Hai-Juan 2,4 He, Qiang-Qiang 2 Li, Cen 2 Wei, Li-Xin 2,4 Shang, Jing 1,2,3; Email Address: shangjing21cn@cpu.edu.cn; Affiliation:  1: School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China  2: Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, University of the Chinese Academy of Sciences, Xining 810008, China  3: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China  4: University of Chinese Academy of Sciences, Beijing 100049, China; Source Info: Apr2019, Vol. 234, p112; Subject Term: HEPATOTOXICOLOGY; Subject Term: DIAGNOSIS; Subject Term: LIVER; Subject Term: ANATOMY; Subject Term: ANIMAL experimentation; Subject Term: APOPTOSIS; Subject Term: FISHES; Subject Term: GENE expression; Subject Term: LIVER cells; Subject Term: TIBETAN medicine; Subject Term: MERCURY; Subject Term: MESSENGER RNA; Subject Term: POLYMERASE chain reaction; Subject Term: STAINS & staining (Microscopy); Subject Term: WESTERN immunoblotting; Subject Term: PLANT extracts; Subject Term: CASPASES; Subject Term: CELL viability; Subject Term: CYTOCHROME P-450; Author-Supplied Keyword: Hepatocytes; Author-Supplied Keyword: Hepatotoxicity; Author-Supplied Keyword: HgS; Author-Supplied Keyword: Zebrafish; Author-Supplied Keyword: Zuotai; NAICS/Industry Codes: 416210 Metal service centres; NAICS/Industry Codes: 212299 All Other Metal Ore Mining; Number of Pages: 7p; Document Type: Article; Full Text Word Count: 5608
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Abstract: (Show)
Abstract Ethnopharmacological relevance Zuotai (gTso thal) has a long history in the treatment of cardiovascular disease, liver and bile diseases, spleen and stomach diseases as a precious adjuvant in Tibetan medicine. However, Zuotai is a mercury preparation that contains 54.5% HgS. Its application has always been controversial. Aim of the study To evaluate the toxicological effects of Zuotai in hepatocytes and in zebrafish. Materials and methods MTT was used to determine the survival rate of hepatocytes; Hoechst and TUNEL staining were used to detect the apoptosis cells; Western blot and RT-qPCR assay were used to determine the expression levels of the protein and mRNA; Liver morphology observation and H&E staining were used to evaluate the hepatotoxicity of Zuotai in Zebfrafish. Results The survival rate of L-02 cells, HepG2 cells and RBL-2A cells reduced by Zuotai (10−4–0.1 mg/mL) in a dose and time-dependent manner. Zuotai (0.1 mg/mL) induced HepG2 cells shrinkage, condensation and fragmentation and increased the number of apoptosis cells. The protein expression levels of cleaved Caspase-3 and Bax were increased and the expression levels of Bcl-2 were reduced after HepG2 cells exposed to Zuotai (10−4–0.1 mg/mL) for 24 h. In addition, Zuotai (0.2 mg/mL) induced the darker liver color of the larval zebrafish and changed the liver morphologic of adult zebrafish. Zuotai (0.2 mg/mL) also increased the mRNA levels of CYP1A1, CYP1B1 and MT-1 in the liver of adult zebrafish. However, no significantly hepatotoxicity was observed after hepatocytes and zebrafish exposed to HgS at the same dose. Conclusions Results showed that Zuotai induced hepatotoxicity effectively under a certain dose but its hepatotoxicity likely occurs via other mechanisms that did not depend on HgS. Graphical abstract Zuotai, a clinical adjuvant in Tibetan medicine, contains 54.5% HgS, which can induce apoptosis of liver cells and liver injury in zebrafish. However, HgS, the principal component of Zuotai did not exhibit hepatotoxicity at the same dose. fx1 [ABSTRACT FROM AUTHOR]