Changes in liver nucleotide concentrations in experimental liver injury. 1. Carbon tetrachloride poisoning

Background/Aims: Swertiamarin (STM), the main bioactive component in Swertia mussotii Franch (Gentianaceae), has been shown to exert hepatoprotective effects on experimental liver injury. However, the effects and exact mechanisms of STM on carbon tetrachloride (CCl4) causing hepatotoxicity are still unknown. This study investigated the potential protective effects and mechanisms of STM on CCl4-induced liver injury in rats. Methods: Adult male Sprague-Dawley (SD) rats were exposed to CCl4 with or without STM co-administration for consecutive eight weeks. Results: STM significantly ameliorated CCl4-induced increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and histopathological changes in the liver. Hepatic oxidative stress was repressed by STM, as evidenced by the decrease in malondialdehyde (MDA), with concomitant increase in antioxidase activity (e.g. superoxide dismutase (SOD); glutathione peroxidase (GPx)), glutathione (GSH) level. STM also obviously attenuated inflammatory response in CCl4-lesioned livers as evidenced by the decrease in inflammatory cytokines/ chemokines (e.g. inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β)). Additionally, STM significantly induced the expression of CYPs, efflux transporters and PDZK1 as compared with the CCl4 group. Moreover, co-administration of STM with CCl4 remarkably up-regulated the expression of Nrf2, HO-1 and NQO1 compared with the CCl4 group. Conclusions: The present study demonstrates that STM exerts a protective effect against CCl4-induced liver injury and inflammation with its antioxidant effects and induction of hepatic detoxification enzymes and efflux transporters expression, at least in part, via the Nrf2/HO-1 pathway in rats.

Download Full-text

Effects of Total Triterpenoids Extract from Ganoderma Iucidum (Curt.: Fr.) P. Karst. (Reishi Mushroom) on Experimental Liver Injury Models Induced by Carbon Tetrachloride or D-Galactosamine in Mice

International Journal of Medicinal Mushrooms ◽

10.1615/intjmedmushr.v4.i4.70 ◽

2002 ◽

Vol 4 (4) ◽

pp. 6 ◽

Cited By ~ 4

Author(s):

Zhi-Bin Lin ◽

Ming-Yu Wang ◽

Qiang Liu ◽

Qing-Ming Che

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Injury Models ◽

Experimental Liver

Download Full-text

The pro‐fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride‐induced experimental liver injury

Immunology and Cell Biology ◽

10.1038/icb.2016.116 ◽

2016 ◽

Vol 95 (5) ◽

pp. 443-453 ◽

Cited By ~ 14

Author(s):

Xin M Wang ◽

Lauren E Holz ◽

Sumaiya Chowdhury ◽

Shaun P Cordoba ◽

Kathryn A Evans ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Experimental Liver

Download Full-text

Mechanism of action of carbon tetrachloride on liver cells

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1954.0024 ◽

1954 ◽

Vol 142 (907) ◽

pp. 241-257 ◽

Cited By ~ 80

Keyword(s):

Carbon Tetrachloride ◽

Mode Of Action ◽

Tricarboxylic Acid Cycle ◽

Pyridine Nucleotide ◽

Respiratory Enzymes ◽

Carbon Tetrachloride Poisoning ◽

Whole Cells ◽

Cell Fractions ◽

Experimental Liver

Carbon tetrachloride has long been used to produce experimental liver necrosis, but its mode of action is obscure. In the present work we have investigated the behaviour of the respiratory enzymes in carbon tetrachloride poisoning, using whole cells and cell-free systems obtained by the method of differential centrifugation. Of the cell fractions, the mitochondria were found to be the component attacked by the poison. We have been able to show that the tricarboxylic acid cycle is disorganized. The earliest changes occur between 10 and 15 h after the poison is administered, and consists of inhibition of the oxidation of citrate, malate, octanoate, pyruvate and glutamate, but at this time the oxidation of succinate is unimpaired. The inhibition of malate, glutamate and citrate oxidation can be reversed by the addition of pyridine nucleotide. In the case of pyruvate the inhibition may be partially reversed by the addition of Co I and ATP. The poisoned mitochondria lose pyridine nucleotide at an abnormally fast rate, and at differing times for the different enzymes. Conversely, we have shown that Co I penetrates poisoned mitochondria at a faster rate than normal mitochondria. Administration of choline to poisoned animals delays both the microscopic appearances of injury and the biochemical changes. We have reproduced the biochemical effects of carbon tetrachloride by in vitro treatment of liver homogenates, and we suggest that the mode of action of the agent is a direct attack on the mitochondria. This attack results in a disorganization of the enzyme systems, and is not a specific inhibition of any one of them. The rate of incorporation of 32 P into mitochondrial phospholipid has also been studied, and found to be somewhat increased in carbon tetrachloride poisoning.

Download Full-text

Ameliorative Effect of Traditional Chinese Medicine Prescriptions on α-Naphthylisothiocyanate and Carbon-tetrachloride Induced Toxicity in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x97000226 ◽

1997 ◽

Vol 25 (02) ◽

pp. 185-196 ◽

Cited By ~ 10

Author(s):

Chin-Chuan Tsai ◽

Shung-Te Kao ◽

Chao-Tien Hsu ◽

Chun-Ching Lin ◽

Jim-Shoung Lai ◽

...

Keyword(s):

Chinese Medicine ◽

Carbon Tetrachloride ◽

Traditional Chinese Medicine ◽

Liver Injury ◽

Serum Total Bilirubin ◽

Glutamate Pyruvate Transaminase ◽

Ameliorative Effect ◽

Glutamate Pyruvate ◽

Experimental Liver ◽

Elevated Lipid

Syh-Mo-Yin (SMY), Guizhi-Fuling-Wan (GFW), Shieh-Qing-Wan (SQW) and Syh-Nih-San (SNS) are prescriptions of Traditional Chinese Medicine (TCM) for liver disease. The effects of these four prescriptions against experimental liver injury induced by α-Naphthylisothiocyanate (ANIT) and carbon tetrachloride ( CCl 4) were studied. Rats treated with ANIT (100 mg/kg) exhibited elevations of serum total bilirubin (TBI), alkaline phosphatase (ALP), glutamate-oxalatetransaminase (sGOT) and glutamate-pyruvate-transaminase (sGPT) as well as cholestasis and parenchymanecrosis. In rats receiving SMY, SQW and SNS treatment after ANIT challenged, the biochemical and morphological parameters of liver injury were significantly reduce. Elevated lipid peroxidation (LPO) level in liver tissue, associated with an increase in serum GOT and GPT level, was observed in CCl 4-treated rats. Treatment with these four prescriptions on CCl 4-induced liver injury rats showed a remarkable hepatoprotective effect. A significant decrease in peroxidative level suggested that these prescriptions have anti free radical properties.

Download Full-text