ABSTRACT
Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.
ABSTRACT
AIM To observe the relationship between dose effect and time effect on hepatoxicity of Gardenia jasminoides Ellis extract in rats.MOTHODS Wistar rats were divided into four groups:low,middle and high (3,10,and 30 g/kg) dose of G.Jasminoides groups (administrated by gavage),and the normal control group were orally given deionized water.All rats were observed daily during the administration period.On the 7th,14th,28th day after the administration,blood samples were collected;serum alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),glutamic dehydrogenase (GLDH) activity and total bile acid (TBA) and total bilirubin (TBIL) were determined.The livers were weighed and the liver index was calculated.HE staining and observation of histopathological changes in the structure of liver tissue under light microscopy were performed.RESULTS After the 7th day of administration,the rats in high dose group showed lower food consumption and slowly increased body weight.Serum ALT,AST,ALP,TBA,TBIL and GLDH in rats from high dose group were significantly higher than those in the normal control group.The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group.After the 14th day of administration,serum ALT,TBA and TBIL in rats from the high dose group were significantly higher than those in the normal group.The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group.After 28th day of administration,serum ALT and TBA in the rats from the high dose group,TBIL and GLDH in rats from the middle dose group,and GLDH in rats from the low dose group were significantly higher than those in the normal control group.The liver indexes of rats in all dose groups were significantly increased than those in the normal control group.After the 7th,14th or 28th day of the treatment,histopathological changes such as the liver cell hypertrophy,interlobular bile duct hyperplasia,and inflammatory cell infiltration appeared in the middle and high dose groups.CONCLUSION The high dose of G.jasminoides can induce and increase liver toxicity with the increase in dose,but at high dose level,liver toxicity does not increase with time.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of single administration of mercury- containing preparation Jiuyi Dan (calcined gypsum-Shengdan 9: 1) and Shengdan on acute toxicity of rabbits, in order to assess the safety of tested drugs.</p><p><b>METHOD</b>The rabbits were randomly divided into 4 groups: the calcined gypsum group (excipient control), the Jiuyi Dan group, the 90 mg Shengdan group and the 180 mg Shengdan group. After 270 mg of calcined gypsum, 300 mg of Jiuyi Dan, 90 mg of Shengdan, and 180 mg of Shengdan were used on the surface of wounds (5 cm x 5 cm) on two sides of rabbit back for 5 h, the surfaces of wound were washed by water. The bloods were taken from the rabbit hearts before and after the drug administration for 24 h, 72 h, 7 d and 14 d for determining Hg level in blood and liver & kidney function indicators (ALT, AST, CREAT, and BUN). The rabbits were dissected after the drugs treatment for 14 d, and pathological tests were made for their livers and kidneys.</p><p><b>RESULT</b>Compared with the calcined gypsum group, the 90 mg Shengdan group and the 180 mg Shengdan group showed significant increase (P < 0.01 or P < 0.05), as evidenced by increase in CREAT for 24 h and 72 h and increase in BUN for 24 h and on 7 d. AST is significantly increased as well (P < 0.01) for 24 h and 72 h compared to that of the group before drug treatment. The Hg level in blood was significantly enhanced (P < 0.01) after the rabbits were administrated with drugs for 24 h to 72 h. The pathological changes in livers and kidneys of rabbits were observed in the two doses of Shengdan treatment groups.</p><p><b>CONCLUSION</b>The Hg blood levels were increased significantly in an obvious dose-effect relationship in all drugs treatment groups. Liver & kidney function indicators were influenced by Shengdan treatment to some extent. Meanwhile, pathological changes in rabbit livers and kidneys were also caused by Shengdan, while Jiuyi Dan has no significantly effect on livers and kidneys.</p>