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1.
Frontiers of Medicine ; (4): 594-607, 2021.
Article in English | WPRIM | ID: wpr-888746

ABSTRACT

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.


Subject(s)
Adenosine Triphosphate , Animals , Chemical and Drug Induced Liver Injury/etiology , Flavonoids , Humans , Inflammasomes , Mice , NLR Family, Pyrin Domain-Containing 3 Protein , Nigericin
2.
Acta Pharmaceutica Sinica ; (12): 1789-1796, 2021.
Article in Chinese | WPRIM | ID: wpr-887018

ABSTRACT

An immunologically stressed rat model was used in a metabolomics study on the ability of Paeoniae Rubra Radix to reduce the liver toxicity of Psoraleae Fructus. Different groups of rats were given the extracts of Psoraleae Fructus and Psoraleae Fructus together with Paeoniae Rubra Radix or combined with a non-toxic dose of lipopolysaccharide (LPS). The biochemical indices of liver function and pathological changes in liver tissue were used to evaluate histopathological changes. UHPLC-QTOF/MS was used to analyze the metabolic profile of serum samples, combined with principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. The HMDB database and Metabo Analyst online tool were used for biomarker identification and metabolic pathway-enrichment analysis. The results show that the co-treatment Psoraleae Fructus and LPS resulted in significant liver injury, indicated by the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as obvious pathological changes. Liver injury was significantly decreased by treatment with Paeoniae Rubra Radix. Metabolomic analysis showed that the addition of Paeoniae Rubra Radix ameliorated the abnormal serum metabolism in rats mainly through regulation of arachidonic acid metabolism and glycerophospholipid metabolism pathways.

3.
Acta Pharmaceutica Sinica ; (12): 1544-1550, 2021.
Article in Chinese | WPRIM | ID: wpr-881551

ABSTRACT

Idiosyncratic drug-induced liver injury (IDILI) is an unpredictable serious adverse drug reaction, which only occurs in a minority of special susceptible individuals. Although the mechanism of IDILI has not been fully understood, several hypotheses have been proposed to explain the action mode and specific mechanism of IDILI. Of these hypotheses, inflammatory stress hypothesis is one of the most important theories. Under the condition of inflammatory stress, drugs interact with inflammation and mediate the occurrence of IDILI through a variety of mechanisms, which can induce the production of inflammatory cytokines, activate coagulation system, affect the activity of metabolites, induce cholestasis, affect mitochondrial damage, and others. This review will summarize the main mechanisms and influencing factors of IDILI mediated by inflammatory stress, in order to provide a reference for preclinical drug development and basic research on drug-induced liver injury.

4.
Acta Pharmaceutica Sinica ; (12): 808-815, 2021.
Article in Chinese | WPRIM | ID: wpr-876533

ABSTRACT

In this study, a composite cell model for evaluation of idiosyncratic drug-induced liver injury (IDILI) was established in vitro from the perspective of immune inflammation. And this model was used to evaluate the risk of IDILI for 2,3,5,4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside (Cis-SG) and 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside (Trans-SG). To determine the low, medium, and high dosage of Cis-SG and Trans-SG, CellTiter-Glo® 3D Cell Viability Assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of HepG2 cells in three dimensional (3D) culture, and MTT assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of THP-1 derived macrophages. THP-1 derived macrophages were incubated by Cis-SG and Trans-SG directly or supernatants from HepG2 cells incubated with them. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-1β (IL-1β) in the supernatants of the THP-1 derived macrophages. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in THP-1 derived macrophages. The results showed that there was no effect on the secretion of IL-1β in THP-1 derived macrophages incubated by Cis-SG and Trans-SG directly. However, the secretion of IL-1β, the protein and mRNA expression of ASC, NLRP3, caspase-1, and IL-1β significantly increased in THP-1 derived macrophages incubated by supernatants from HepG2 cells incubated with 1, 5, and 25 μmol·L-1 Cis-SG or 25 μmol·L-1 Trans-SG. In summary, the composite cell model for evaluation of IDILI established in vitro has been successfully applied in testing Cis-SG and Trans-SG. This composite cell model is helpful to evaluate and screen drugs with IDILI risk in vitro preliminarily, which provides methods for predicting and solving the idiosyncratic liver toxicity of drugs.

5.
Article in Chinese | WPRIM | ID: wpr-873022

ABSTRACT

Objective:To investigate the pharmaceutical idiosyncratic hepatotoxicity effect of Xanthii Fructus on the immune-sensitive rat model induced by endotoxin lipopolysaccharide (LPS). Method:The SD rats were randomly divided into five groups: control group, model group, and three Xanthii Fructucs groups. The immune-sensitive rat model was established by LPS (iv. 0.7 mg·kg-1, twice every 7 days). Then, the rats in control and model groups received the equal volume of distilled water, while the rats in Xanthii Fructus groups were administrated with water extract of Xanthii Fructus intragastrically (1.67, 5.01, 16.7 g·kg-1, respectively) for 14 days. The serum and liver of the rats were collected on the 7th and 14th day to examine the levels of hepatotoxic biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), alkaline phosphatase (ALP), and total bile acids (TBA), and liver histopathology. In addition, inflammatory factors, including interleukin-1β(IL-1β), interleukin-2(IL-2), interleukin-6(IL-6), interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)of the idiosyncratic hepatotoxicity rats, were determined by enzyme-linked immunosorbent assay(ELISA). Result:The immune-sensitive model rats showed elevated levels of IL-1β, IL-6(P<0.05,P<0.01), and mild inflammatory cells infiltrated in portal area of liver significantly (P<0.05), with no significant changes in hepatotoxic biomarkers. Meanwhile, there was no significant change between Xanthii Fructus groups and model rats in the levels of hepatotoxic biomarkers, inflammatory factors and hepatic lesions. Conclusion:Water extract of Xanthii Fructus intragastrically does not affect the levels of hepatotoxic biomarkers, inflammatory factors and hepatic lesions in rats induced by LPS intravenously. That is to say, Xanthii Fructus does not induce pharmaceutical idiosyncratic hepatotoxicity.

6.
Article | IMSEAR | ID: sea-211849

ABSTRACT

Paracetamol is a commonly used antipyretic and analgesic with a weak anti-inflammatory action with a good safety profile in children and adults. This has resulted in its over prescription and large over the counter sale. Thus, adverse drug reactions due to paracetamol may be easily overlooked resulting in delay in diagnosis. Author present a case report of a 12 year old boy with bullous fixed drug eruptions due to paracetamol while he tolerated NSAIDS well. This highlights the need of adverse drug reaction monitoring and reporting, for early detection and prompt treatment of drug related morbidity and the cautious use of even the most commonly used drugs.

7.
Acta Pharmaceutica Sinica ; (12): 678-686, 2019.
Article in Chinese | WPRIM | ID: wpr-780153

ABSTRACT

Using the idiosyncratic lipopolysaccharide (LPS)-mediated hepatotoxicity model as a positive control, liver injury induced by Cortex Dictamni aqueous extract (AE) or Cortex Dictamni ethanol extracts (EE) was evaluated. Idiosyncratic hepatotoxicity model was established in rats [Institutional Animal Care and Use Committee (IACUC)-2018-008] by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into 10 groups. The plasma levels of liver function biomarkers such as alanine transaminase (ALT), aspartate aminotransferase (AST) were measured. Histological changes (HE staining), hepatocellular apoptosis and the content of cytokines of liver were measured. Network pharmacology was used to analyze the relationship between chemical components and immunity in Cortex Dictamni. Compared with the control group, the doses (25, 50 g·kg-1) of AE or EE had no significant changes in ALT, AST and liver pathology (P>0.05). The doses of 4.2 g·kg-1 of AE or EE+LPS groups exhibited an elevation in ALT, AST and serum cytokines (P<0.01). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in these groups. Network pharmacology shows that Cortex Dictamni may directly or indirectly participate in the process of immunomodulation. We found that Cortex Dictamni regulated 15 core targets and affected 19 pathways, including apoptosis, TNF-α, NF-kappa B signaling pathways. These results suggest that Cortex Dictamni can induce idiosyncratic hepatotoxicity and the water extract can induce more serious liver injury then ethanol extract of Cortex Dictamni. These findings provide a reference for elucidating the idiosyncratic hepatotoxicity induced by Cortex Dictamni.

8.
Article in Chinese | WPRIM | ID: wpr-852078

ABSTRACT

Objective: To analyze the correlation of idiosyncratic hepatotoxicity of Zhuangguguanjie Wan (ZGW) with 27 cytokines. Methods: After 12 h fasting, SD rats were ig with ZGW at a single dose of 3.8 g/kg, and injected with lipopolysaccharide (LPS) at a dosage of 2.8 mg/kg via tail vein after 2 h. The rats were anesthetized with chloral hydrate after 10 h LPS administration, and then the blood samples were collected from the inferior vena cava and liver tissue was also obtained. Alanine aminotransferase (ALT) activity in serum and levels of 27 cytokines in liver tissue were tested. Correlation analysis of ALT and cytokines were performed using R 3.2.4 software. Results: Correlation analysis showed that there was a high positive correlation between ALT and macrophage inflammatory protein-1α (MIP-1α) or vascular endothelial growth factor (VEGF). There was a strong correlation among interleukin-18 (IL-18), interferon-inducible protein-10 (IP-10), interleukin-1α (IL-1α), and interleukin-1β (IL-1β). However, eotaxin regulated upon activation of normal T cell expression and secreted factor (RANTES), which has their own independence. Conclusion: Idiosyncratic liver injury induced by ZGW has a strong positive correlation with MIP-1α and VEGF, which provides a new experimental evidence for clinical medication safety and risk prevention of ZGW.

9.
Acta Pharmaceutica Sinica ; (12): 574-584, 2018.
Article in Chinese | WPRIM | ID: wpr-779910

ABSTRACT

In this study, we used a mathematic-based modeling system to screen the cytokines that are sensitive to Zhuangguguanjie wan (ZGW)-induced idiosyncratic liver injury. The values of 27 cytokines were used as the data source in rat liver of lipopolysaccharide (LPS) + ZGW group. The alanine aminotransferase (ALT) activity value of liver function indexes was used as the outcome evaluation index of liver injury. Cytokines of ZGW-induced idiosyncratic liver injury were screened using Logistic regression, random forest method, LASSO Logistics regression and method of combining rule discovery algorithm with LASSO, and cytokines filtered out were revalued in THP1 macrophage. Susceptible cytokine combinations:interleukin-1β (IL-1β), epidermal growth factor (EGF) and interleukin-18 (IL-18) closely related to ZGW-induced idiosyncratic liver injury were obtained after preliminary screening analysis. The result of revalued in THP1 showed that the ethanolic extract of ZGW (EtZ) combined with IL-1β or IL-18 synergistically enhanced tumor necrosis factor-α (TNF-α) secretion in THP1 macrophage, and EtZ combined with IL-1β significantly enhanced interleukin-6 (IL-6) secretion in THP1 macrophage, but EtZ combined with EGF markedly inhibited IL-6 secretion in THP1 macrophage. The results suggest that the sensitive cytokines that can be characterized in the ZGW-induced idiosyncratic liver injury are IL-1β and IL-18, which provides a basis for screening the ZGW-induced idiosyncratic liver injury patients, and a new experimental evidence for clinical safety medication and risk prevention of ZGW.

10.
Article in Korean | WPRIM | ID: wpr-186777

ABSTRACT

PURPOSE: To report a case involving an unexpected increase in intraocular pressure (IOP) and acute angle closure after oral administration of methazolamide. CASE SUMMARY: A 38-year-old male visited the emergency department complaining of decreased visual acuity (VA) and ocular pain. These symptoms developed after he took two tablets of 50 mg methazolamide because his IOP was above normal after a short course of systemic steroid treatment. His uncorrected VA dropped to 0.04 and the refractive error was −6.5 diopters in both eyes. The anterior chamber was very shallow, and the IOPs were 46 mmHg in the right eye and 42 mmHg in the left eye. Macular retinal folds were observed in both eyes in infrared fundus images. The patient was instructed not to take methazolamide, which was suspected as the cause of this idiosyncratic drug reaction. He was prescribed topical anti-glaucoma medications and cycloplegics to relieve the acute angle closure, and all symptoms disappeared after these treatments. CONCLUSIONS: Methazolamide is a sulfa derivative like topiramate, which can cause acute angle closure involving edema of the ciliary body and anterior displacement of the lens-iris diaphragm. Clinicians should consider this possible IOP increase before prescribing methazolamide.


Subject(s)
Administration, Oral , Adult , Anterior Chamber , Ciliary Body , Diaphragm , Edema , Emergency Service, Hospital , Humans , Intraocular Pressure , Male , Methazolamide , Mydriatics , Refractive Errors , Retinaldehyde , Tablets , Visual Acuity
11.
Article in Chinese | WPRIM | ID: wpr-335814

ABSTRACT

To explore the possible mechanism of liver injury, the effects of Ploygoni Multiflori Caulis and its extractive on the function of bilirubin-associated transporters were investigated in normal (N) and idiosyncratic (LPS) rats (M). The normal and LPS rats were respectively administrated powder of Ploygoni Multiflori Caulis, its extractive and same volume of 0.5% CMC-Na solution for 7 d. BSP, a substrate of the transporters of Oatp1a1 and Oatp1b2 was selected, and its pharmacokinetic parameters of intravenous injection were determined to examined the activity these transporters. Meanwhile the mRNA expressions of transporters were detected. Compared with N-blank control group, besides M-powder group, the Cmax has no significantly different from other groups, t1/2, AUC0-t and AUC0-∞ were significantly increased, and CL were significantly decreased. However, compared with N- blank control group, AST and ALT decreased significantly. The expression of Oatp1a1, Oatp1b2 and MRP2 mRNA was significantly decreased (P<0.05), but there was no act synergistically when Ploygoni Multiflori Caulis and extractive were combined with LPS. The function of Oatp1a1, Oatp1b2 and MRP2 in rats were significantly inhibited by Ploygoni Multiflori Caulis and extractive, which may be an important cause of hepatotoxicity.

12.
Article in Chinese | WPRIM | ID: wpr-853070

ABSTRACT

Objective: To investigate the protective effect of Liuweiwuling Tablets of Polygonum multiflorum (PM)-induced idiosyncratic hepatotoxicity. Methods: Eighty Sprague-Dawley (SD) rats were randomly divided into control group, LPS group, PM group, LPS + PM group, LPS + PM + Liuweiwuling Tablets low, medium, and high dose (0.4, 0.8, and1.6 g/kg) groups, and LPS + PM + positive drug Biphenyl group (2 mg/kg). All groups were orally given Liuweiwuling Tablets and Biphenyl once daily for consecutive 2 d according to the different dosages. On day 3, except the normal group and LPS group oral administration of distilled water, all groups were given PM (crude drug 2.16 g/kg), 3 h after the group by the tail vein injection LPS (2.8 mg/kg) according to the different dosage; After 7 h, the rats were anesthetized with sodium pentobarbital, and the inferior vena cava was used to collect blood and liver tissue samples were collected. HE staining was used to observe the pathological changes of liver tissue, and the contents of ALT, AST, TNF-α, IL-1β, IL-6, and IFN-γ in rat plasma were determined. TUNEL assay analyzed hepatocyte apoptosis, and immunohistochemical staining was performed to detect the liver tissue expression activity of NF-κB p65. Results: Liuweiwuling Tablets could decrease ALT and AST levels of PM-induced idiosyncratic liver injury rat plasma, reduce liver pathological injury and hepatocyte apoptosis, inhibit the expression of NF-κB p65, and decrease plasma TNF-α and other inflammatory cytokines. Conclusion: Liuweiwuling Tablets can reduce inflammation through the inhibition of NF-κB signaling pathway, and prevent of PM induced idiosyncratic liver injury.

13.
Acta Pharmaceutica Sinica ; (12): 1069-1076, 2017.
Article in Chinese | WPRIM | ID: wpr-779696

ABSTRACT

It is investigated that the hepatotoxicity of Polygonum multiflorum (PM)was attenuated by its processed products of nine times steaming and nine times sunning(RPM)based on immunological stress-mediated animal model by using metabolomics method. Sprague-Dawley(SD)rats were intragastrically administered with(5.4 g crude drug per kg body weight)of 50% alcohol extracts of PM and its processed products of nine times steaming and nine times sunning respectively or co-treated with non-toxic dose of lipopolysaccharide(LPS, 2.8 mg·kg-1)via tail vein injection. The plasma alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were assayed and the isolated livers were evaluated for histopathological changes. Global metabolomics profiling, multivariate analysis and data base searching were performed to discover common differential metabolites for idiosyncratic liver injury. The results showed that co-treatment with non-toxic dose of LPS and PM could result in significant liver injury, indicated by the elevation of plasma ALT and AST activities, as well as obvious liver histologic damage; whereas RPM failed to induce detectable liver injury. Furthermore, 10 potential metabolomics biomarkers that differentially expressed in LPS/PM group compared with LPS/RPM without liver injury were identified by untargeted metabolomics, mainly involved ten pathways: sphingolipid metabolism, linoleic acid metabolism, taurine and hypotaurine metabolism, steroid hormone biosynthesis, galactose metabolism, steroid biosynthesis, metabolism of xenobiotics by cytochrome P450, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis. This work illustrated the idiosyncratic hepatotoxicity of heshouwu and provided a metabolomic insight into diosyncratic liver injury of PM and RPM.

14.
Acta Pharmaceutica Sinica ; (12): 1041-1047, 2017.
Article in Chinese | WPRIM | ID: wpr-779692

ABSTRACT

This study was designed to investigate the correlation between idiosyncratic liver injury and content of cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(cis-SG)in radix Polygoni multiflori Preparata(RPMP). In order to compare the effect of hepatotoxicity of different cis-SG contents in RPMP, rats were administered with 50% alcohol extracts of RPMP(7.56 g·kg-1, via intragastric administration)alone or co-treated with lipopolysaccharide(LPS, 2.8 mg·kg-1, via tail vein injection). The results showed that no significant alterations of plasma ALT and AST activities were observed in the normal rats. In the LPS treated rats, the group without light treatment and the group with 0.10% cis-SG after light treatment did not exhibit obvious injury in liver. The group with 0.35% cis-SG after light treatment and the group with 0.70% cis-SG after light treatment showed significant increases in ALT, AST, TNF-α, IL-6, NF-κB p65 and apoptosis rate(P < 0.05), causing pathological changes in the liver tissue. Through the content analysis of drug in patients with liver injury, we found that the content of cis-SG(> 0.40%)was generally higher than that of pieces collected from different origins(< 0.10%). The comparative analysis of experiments and clinical data showed that there was a relationship between the content of cis-SG and idiosyncratic liver injury. In order to reduce the risk of clinical medication, the content of cis-SG of 0.10% should be a limit of quality control in the production processing of Polygonum multiflorum.

15.
Acta Pharmaceutica Sinica ; (12): 1033-1040, 2017.
Article in Chinese | WPRIM | ID: wpr-779691

ABSTRACT

On basis of the idiosyncratic lipopolysaccharide(LPS)-mediated hepatotoxicity model, liver injury induced by Zhuangguguanjie wan(ZGW)was evaluated, and the mechanism was explored. Idiosyncratic hepatotoxicity model was established in rats by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into the normal control group, LPS group, ZGW group and LPS+ZGW group. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were analyzed in serum; pathological changes(HE staining)and the content of cytokines of liver were tested; and immune cell subpopulation ration were determined in blood and liver. Compared with the control group, the ZGW group and LPS group had no significant changes in ALT, AST and liver pathology(P> 0.05); while the ZGW+LPS group exhibited an elevation in ALT and AST(P< 0.05). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in the group. Several cytokines in the liver were increased in LPS group and ZGW+LPS group(P< 0.05 or P< 0.01), and the level in ZGW+LPS group was higher than that of LPS group. Compared with the control group, the ratio of CD3+ T cell/lymphocyte of blood in LPS group was significantly decreased(P< 0.01); while the percentage of CD3+ T cells in the liver were significantly increased(P< 0.05). The contents of immune cells of blood had no significant changes between LPS group and ZGW+LPS group(P> 0.05). CD3+ T cell in the liver of ZGW+LPS group was significantly increased over the LPS group(P< 0.05). Aggregation or activity of CD3+ T cell was increased by ZGW combined with LPS. These results suggest that ZGW could promote T lymphocyte recruitment to liver under the immune activation state leading to inflammatory response, which may contribute to idiosyncratic liver injury.

16.
Acta Pharmaceutica Sinica ; (12): 1027-1032, 2017.
Article in Chinese | WPRIM | ID: wpr-779690

ABSTRACT

To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.

17.
Acta Pharmaceutica Sinica ; (12): 1019-1026, 2017.
Article in Chinese | WPRIM | ID: wpr-779689

ABSTRACT

Idiosyncratic drug-induced liver injury(IDILI)is an adverse drug reaction that occurs only in a minority of the population. IDILI also has many characteristics such as unpredictable and low morbidity, its occurrence has often not been clearly correlated with the dose, route, or duration of drug administration. Several studies have shown that IDILI is a synergistic effect which was caused by body diathesis, environment and drugs. In addition, evidence also suggests that most IDILIs are mediated by immunity. Chemical medicines-related IDILIs have been extensively studied, and a variety of immunological mechanism hypotheses have also emerged to explain the pathogenesis and characteristics of chemical medicines-related IDILIs. However, the traditional Chinese medicine(TCM)-related IDILI has always been neglected due to the complexity and specificity of TCM. In recent years, TCM-related IDILI has been gradually confirmed by researchers, and formed a new hypothesis, a immunological stress-mediated tri-elements synergetic mechanism hypothesis, which can reveal the pathogenesis and clinical characteristics of TCM-related IDILI. This paper is prepared to summarize the immunological mechanism hypotheses of chemical medicine-related IDILI and TCM-related IDILI to provide a scientific basis for guiding IDILI research and establishing its clinical risk prevention and control measures.

18.
Chinese Pharmaceutical Journal ; (24): 1105-1109, 2017.
Article in Chinese | WPRIM | ID: wpr-858651

ABSTRACT

In recent years, the report of adverse reaction of traditional Chinese medicine(TCM), especially the traditional non-toxic TCM-induced liver injury problems have been repeatedly arising, causing serious concerns about the safety of TCM from the public, and meanwhile there is a huge controversy about the objectivity of traditional non-toxic TCM-induced liver injury as well. How to scientifically acknowledge the side effects of traditional non-toxic TCM has become one of the most challenging and difficult international problems in this field. Previous studies may only focus on the search for toxic substances and toxic mechanisms from the perspective of drugs, so there is little attention and research on the factors that it may be caused by patients' bodies, especially the immune-mediated idiosyncratic drug induced liver injury. This paper carries on the analysis to the TCM-induced liver injury from the angles of objective identification and evaluation problems, elaborates the relationship between the immune and drug-induced liver injury, taking the traditional non-toxic TCM Polygonum Multiflorum as an example to analyze the objective authenticity and mechanism of immune-mediated idiosyncratic drug induced liver injury, on which basis the immunological stress "Three Factors Causing toxicity" mechanism hypothesis of idiosyncratic TCM-induced liver injury has been frist put forward. This hypothesis also provides a theoretical basis for the objective identification and evaluation of traditional non-toxic TCM-induced liver injury, innovate and develop a new evaluation model and method of TCM's safety, which has a significant value for revealing the objectivity of TCM-induced liver injury.

19.
Article in Chinese | WPRIM | ID: wpr-335897

ABSTRACT

Idiosyncratic drug-induced liver injury (IDILI) is a kind of unique adverse drug reaction with relative high morbidity compared with other idiosyncratic diseases. Its occurrence, however, has nothing to do with pharmacological effects and clinical dosage of drugs administered, and only a small number of susceptible individuals will suffer from it. Especially to deserve to be mentioned, the proportion of TCM-induced IDILI showed an ascending trend year by year. So in this article, the author has reviewed some facts related with TCM-induced IDILI, including the predisposing causes and occurrence mechanism, and tries to provide reference for the prevention, diagnosis and treatment of TCM-induced IDILI through the analysis of characteristics and research status of TCM-induced IDILI and exploration of the internal relationship between Chinese medicine constitution type and IDILI.

20.
Rev. colomb. gastroenterol ; 31(4): 438-442, oct.-dic. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-960041

ABSTRACT

La isoniazida se utiliza para el tratamiento o profilaxis de la tuberculosis; sin embargo, su uso puede asociarse con reacciones hepáticas adversas. La hepatitis clínicamente manifiesta sucede en 0,5%-1% de los pacientes que reciben isoniazida como monoterapia. En este artículo se describe el caso de un paciente con enfermedad de Crohn que cursó con hepatotoxicidad grave por isoniazida, y se hace una revisión de la literatura al respecto


Isoniazid is used for treatment or prophylaxis of tuberculosis but may be associated with adverse hepatic reactions. Clinically manifest hepatitis occurs in 0.5%-1% of patients who receive isoniazid as monotherapy. This article describes the case of a patient with Crohn’s disease who experienced severe hepatotoxicity due to isoniazid. It also reviews the literature.


Subject(s)
Humans , Male , Middle Aged , Crohn Disease , Hepatitis , Isoniazid , Literature
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