The aim of the present study was to investigate whether pretreatment with the Japanese herbal medicine, "Juzen-taiho-to" (JTX), had an ameliorative effect on carbon tetrachloride (
BackgroundThe current study aimed to investigate the hepatoprotective effects of Sasa veitchii extract (SE) on carbon tetrachloride (CCl4)-induced liver fibrosis in mice.MethodsMale C57BL/6J mice were intraperitoneally injected with CCl4 dissolved in olive oil (1 g/kg) twice per week for 8 weeks. SE (0.1 mL) was administered orally once per day throughout the study, and body weight was measured weekly. Seventy-two hours after the final CCl4 injection, mice were euthanized and plasma samples were collected. The liver and kidneys were collected and weighed.ResultsCCl4 administration increased liver weight, decreased body weight, elevated plasma alanine aminotransferase, and aspartate aminotransferase and increased liver oxidative stress (malondialdehyde and glutathione). These increases were attenuated by SE treatment. Overexpression of tumor necrosis factor-α was also reversed following SE treatment. Furthermore, CCl4-induced increases in α-smooth muscle actin, a marker for hepatic fibrosis, were attenuated in mice treated with SE. Moreover, SE inhibited CCl4-induced nuclear translocation of hepatic nuclear factor kappa B (NF-κB) p65 and phosphorylation of mitogen-activated protein kinase (MAPK).ConclusionThese results suggested that SE prevented CCl4-induced hepatic fibrosis by inhibiting the MAPK and NF-κB signaling pathways.
When multiple drugs or chemicals are used in combination, it is important to understand the risk of their interactions and predict potential additive effects. The aim of the current study was to investigate the molecular mechanism(s) accounting for the additive/synergistic effect of combination treatment with acetaminophen (APAP) and carbon tetrachloride (CCl). Mice were intraperitoneally administered vehicle or 100 mg/kg (5 mL/kg) APAP and 30 min after vehicle or 15 mg/kg (5 mL/kg) CCl. Sixteen hours after treatment, mice from each group were sacrificed and the livers were removed. CCl administration caused slight glycogen depletion; this effect was more pronounced following co-administration of APAP and CCl. ATP and NADPH levels showed the same trend as glycogen levels. The levels of receptor interacting protein 1 and 3 increased following combination treatment with APAP and CCl. In contrast, levels of the glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modifier subunits were not significantly affected by combination treatment. APAP and CCl co-administration potentiated the phosphorylation of c-Jun N-terminal kinase and p38 kinases, although phosphorylated activation of extracellular signal-regulated kinase was not changed. Our results suggest that APAP and CCl co-administration potentiates hepatotoxicity in an additive/synergistic manner via receptor interacting protein activation.
-The aim of this study was to investigate whether the Japanese herbal medicine "Juzen-taiho-to (JTX)" has a protective effect on ethanol (EtOH)-induced liver injury. Seven-week-old male ICR mice were orally administered JTX or saline once a day for three days. Twenty-four hours after the last administration, the mice were intraperitoneally injected with EtOH (2 g/kg). The mice in each group were killed 24 hr after EtOH administration and were bled to obtain plasma. The mice injected with EtOH had high plasma levels of alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. Histopathological examination of the liver of mice treated with EtOH revealed an abnormal outline around the central vein, glycogen depletion, and expression of prostaglandin-endoperoxide synthase 2. Pretreatment with JTX prevented the EtOH-induced increase in the levels of alanine aminotransferase and aspartate aminotransferase, lipid peroxidation, and histopathological changes. Our results suggest that JTX exerts protective effects against EtOH-induced liver disease by modulating oxidative stress and inflammatory response.
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