OBJECTIVETo explore the influence of exogenous putrescine on the function of liver and apoptosis of liver cells in rats.

METHODSNinety healthy clean SD rats were divided into control group (C, n = 10, intraperitoneally injected with 2 mL normal saline), low dosage putrescine group (LP, n = 40), and high dosage putrescine group (HP, n = 40) according to the random number table. Rats in the latter two groups were intraperitoneally injected with approximately 2 mL putrescine (2.5 or 5.0 g/L) with the dosage of 25 or 50 µg/g. Ten rats from group C at post injection hour (PIH) 24 and 10 rats from each of the latter two groups at PIH 24, 48, 72, 96 were sacrificed. Heart blood was obtained for determination of serum contents of ALT and AST. Liver was harvested for gross observation and histomorphological observation with HE staining. Apoptosis was shown with in situ end labeling, and apoptosis index (AI) was calculated. Data among the three groups and those at different time points within one group were processed with one-way analysis of variance or Welch test; LSD or Dunnett's T3 test was used for paired comparison; factorial design analysis of variance of two factors was applied for data between group LP and group HP.

RESULTS(1) No obvious abnormality was observed at gross observation of liver of rats in each group. Liver tissue of rats in group C was normal. Light edema was observed occasionally in liver of rats in groups LP and HP, but necrotic cells were not seen. (2) Content of ALT at PIH 24, 48, 96 and content of AST at PIH 72 and 96 in group LP were respectively (38 ± 10), (45 ± 6), (34 ± 4), (207 ± 18), (196 ± 19) U/L, and content of ALT at PIH 72 and 96 and content of AST at PIH 24, 72, 96 in group HP were respectively (38 ± 6), (48 ± 5), (213 ± 43), (209 ± 40), (230 ± 29) U/L. They were significantly higher than those of rats in group C [(29 ± 5), (163 ± 42) U/L, with P values all below 0.01]. There were statistically significant differences between group LP and group HP in the content of ALT at PIH 48, 72, 96 and content of AST at PIH 96 (with P values all below 0.05). Compared with that at PIH 24 of each group, content of ALT of rats in group LP at PIH 48 and that of rats in group HP at PIH 96, as well as content of AST of rats in group LP at PIH 48, 72, 96 and that of rats in group HP at PIH 48 were significantly increased or decreased (with P values all below 0.05). Factorial analysis showed that the differences due to different concentration of putrescine on content of AST were statistically significant (F = 12.21, P = 0.001), but not on content of ALT (F = 0.01, P = 0.974) between group LP and group HP. (3) AI values of rats in group LP at PIH 24, 48, 72 were respectively (5.69 ± 0.38)%, (13.80 ± 1.66)%, (11.56 ± 1.74)%, and AI values of rats in group HP at PIH 72 and 96 were respectively (10.29 ± 1.43)%, (15.29 ± 1.41)%. They were all obviously higher than AI value of control group at PIH 24 [(3.50 ± 0.30)%, with P values all below 0.01]. There were statistically significant differences between group LP and group HP in AI value at PIH 24, 48, 96 (with P values all below 0.05). Compared with that at PIH 24 of each group, AI value of rats in groups LP and HP at PIH 48, 72, 96 were significantly increased or decreased (with P values all below 0.05). Factorial analysis showed that the differences in the influence of concentration of putrescine and stimulation time on AI value were statistically significant (with F values respectively 22.95 and 130.44, P values all below 0.01).

CONCLUSIONSIntraperitoneal injection of exogenous putrescine in the dosage of 25 or 50 µg/g could lead to certain degree of functional damage of liver and apoptosis of liver cells of rat. The higher the dosage and the longer the stimulation time, the more obvious the damage and apoptosis would be.

Alanine Transaminase ; blood ; Animals ; Apoptosis ; drug effects ; Hepatocytes ; cytology ; drug effects ; Liver ; cytology ; pathology ; Putrescine ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study skin sensitization as well as liver and kidney impairment in guinea pigs treated with trichloroethylene (TCE).

METHODSGuinea pig maximization test (GPMT) was applied in this study, guinea pigs were divided into 3 groups, namely negative control, positive control and TCE treatment. Animals of 3 groups were administrated with olive oil, 2, 4-dinitrochlorobenzene (DNCB), and TCE, respectively, by intradermal injection. The animal skin was observed and blood was collected after various treatment, the liver function tests were conducted, including detection of activities of ALT, AST, LDH and levels of creatinine, uric acid, and urea with automatic biochemical analyzer.

RESULTSObvious skin impairment was observed in the groups of positive control and TCE treatment, the skin impairment included erythema and edema, the sensitization rate was 100% in positive control and 83.3% in TCE treatment group. Additionally, the activities of ALT, AST and LDH increased significantly in the groups of positive control and TCE treatment when compared with the negative control.

CONCLUSIONSTrichloroethylene is one of the strong hypersensitizing substances, it could induce skin allergic reaction and liver impairment in guinea pigs.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Female ; Guinea Pigs ; Kidney ; drug effects ; Liver ; drug effects ; Skin ; drug effects ; Trichloroethylene ; toxicity

OBJECTIVETo observe the heart damage in 10 patients with acute fluoroacetamide poisoning.

METHODSMonitoring serum activities of myocardial enzymes [creatine kinase (CK), asparate aminotransferase (AST), lactate dehydrogenase(LDH) and hydroxybutyrate dehydrogenase(HBDH)] and recording ECG on these 10 patients were performed during the period of their hospitalization. In the mean while, 24 hour dynamic ECG were also recorded and analysed using GP7000L Holter.

RESULTS(1) Urinary fluorine ion concentrations were increased in 9 patients before therapy and in all these 10 patients during therapeutic period. (2) The activities of serum CK in 2 patients and that of serum HBDH in one patient were increased before therapy. However, the serum activities of one or more than one myocardial enzymes were increased in all these 10 patients during therapeutic period. (3) Four patients had abnormal change of ECG before therapy and 5 patients during therapeutic period. (4) 24 hour dynamic ECG records showed that there were heart electrical alternans in 9 patients. One patient had wandering pacemaker and 6 patients had arythmia.

CONCLUSIONFluoroacetamide may cause obvious heart damage, and also heart electrical alternation.

Acute Disease ; Alanine Transaminase ; blood ; Creatine Kinase ; blood ; Electrocardiography ; drug effects ; Fluoroacetates ; poisoning ; Heart ; drug effects ; Humans ; Hydroxybutyrate Dehydrogenase ; blood ; L-Lactate Dehydrogenase ; blood

In this article, canonical correlation analysis was used to explore the relationship between the toxicity-attenuating effect and the variation of chemical contents in rhubarb caused by processing. With quasi-acute toxicity test, the difference of hepatic and renal toxicity to mice with the processed materials of rhubarb was researched. The chemical contents of anthraquinones and tannins in rhubarb were measured by UV-vis spectrophotometry and high performance liquid chromatography. The results showed that there were toxic effects to liver and kidney in mice after repeated intragastric administration of rhubarb and its processed materials for 14 days at a dosage of 76 g x kg(-1). The toxic effect of processed materials was much lower than crude drug. With canonical correlation analysis, the sequence of the hepatic and renal toxicity of chemical contents in rhubarb were found as follows: total anthraquinone glycosides (AQGs) > tannins (Tns) > total anthraquinones (AQs); aloe-emodin (AE) > physcione (Ph) > rhein (Rn) > emodin (Ed) > chrysophanol (Ch) and AEG > PhG > ChG > EdG > RnG of glycosyl-anthraquinone. It could be concluded that processing would attenuate the toxicity of crude drug of rhubarb. The toxicity-attenuating effect might be correlated to the decline of the contents of both anthraquinone glycosides and tannins, especially the aloe-emodin glycoside and physcione glycoside. The results also suggested that the serum alanine aminotransferase (ALT) and creatine (CREA) would be useful to monitor the hepatic and renal toxicity of rhubarb.
Alanine Transaminase ; blood ; Animals ; Anthraquinones ; analysis ; Creatinine ; blood ; Kidney ; drug effects ; Liver ; drug effects ; Mice ; Plant Roots ; chemistry ; Proanthocyanidins ; analysis ; Rheum ; chemistry ; toxicity ; Technology, Pharmaceutical ; methods

AIMTo explore the role of ligustrazin on dynamic changes of lipid peroxidation in hepatic ischemia/reperfusion injury (HIRI) and its mechanism.

METHODSThe HIRI model was used. Twenty rabbits were randomly divided into control group (n = 10) and ligustrazin group (n = 10). The xanthine oxidase (XO) activity, superoxide dismutase (SOD) activity,malondialdehyde (MDA) content and glutamic pyruvic transaminase (GPT) activity in plasma were observed before ischemia and at ischemia 25 min, reperfusion 25 min, reperfusion 60 min and reperfusion 120 min.

RESULTSThe XO activity, SOD activity, MDA content and GPT activity of ligustrazin group, as compared with control group, showed significant differences (P < 0.05 or P < 0.01) at total time points of reperfusion.

CONCLUSIONLigustrazin has notable anti-lipid peroxidation effect on HIRI, which is due to its inhibiting the generation of oxygen free radicals and its strengthening scavenging of oxygen free radicals.

Alanine Transaminase ; metabolism ; Animals ; Female ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; blood ; Pyrazines ; pharmacology ; Rabbits ; Reperfusion Injury ; metabolism ; Superoxide Dismutase ; metabolism ; Xanthine Oxidase ; metabolism

OBJECTIVETo study the toxicity of water extracts from the fruits of Evodia Fructus in different producing areas.

METHODCompare the toxicity of the extracts from different Evodia Fructus on mice by the methods of acute and subacute toxicity test. The mice were given the extracts for 1 d to test the maximal tolerance dose (MTD) or maximal dose and observe the acute toxic symptoms; The mice were given the extracts for 15 d and then detected the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG). The liver index was calculated, and the liver histological changes were investigated.

RESULTThe MTD of water extracts from the fruits of Evodia Fructus is 62, 44.8, 35.84 g x kg(-1); the MTD of Evodia Fructus is 56, 44. 8, 35.84 g x kg(-1); the maximal dose of Evodia Fructus is 60, 54, 45 g x kg(-1). The toxic symptoms of the mice which had been given the nine samples were almost consistent. Compared with the control group in subacute toxicity test, the level of serum ALT and the liver index were all increased. The liver histological were changed.

CONCLUSIONWhen water extracts from the fruits of Evodia Fructus are given to mice one or more times. It may be toxic and induce liver damage. There is no significant correlation between the toxicity and Evodia orgins, while the toxicity seems to be more closely related to the producing area.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; China ; Drugs, Chinese Herbal ; administration & dosage ; metabolism ; toxicity ; Evodia ; chemistry ; Female ; Fruit ; chemistry ; Liver ; drug effects ; metabolism ; Male ; Mice ; Triglycerides ; blood

OBJECTIVETo observe the effect of fluoroacetamide on cardiomyocytes of rat and the antidotal effect of acetamide.

METHODS4 groups of SD rats were treated with various dosages of fluoroacetamid(p.o.) and 2 groups of them were treated with acetamide(i.p.). The changes of cardiomyocytes and serum AST, LDH, CK, CK-MB and HBDH were measured at different intervals after poisoning.

RESULTSIn the group treated with fluoroacetamid 8 mg/kg. bw, serum AST[(589.58 +/- 821.72) U/L], CK[(916.78 +/- 343.55) U/L], HBDH[(504.47 +/- 148.88) U/L] raised obviously compared with control[(187.70 +/- 46.87), (755.65 +/- 498.90), (347.25 +/- 228.40) U/L respectively] (P < 0.01), and the pathological findings such as degeneration, liquefactive necrosis and filtration of inflammatory cells in cardiac muscles were observed 24 hours later, while all the male dead within 3 days. In the group treated with fluoroacetamid 4 mg/kg. bw, serum LDH and HBDH rose significantly compared with control(P < 0.01) 5 day later. On the day of 10, myocardial enzymes restored in all experiment groups with some interstitial fibroblastic proliferation. The pathological changes were reduced in the group treated with acetamide synchronously (100 mg/kg. bw).

CONCLUSIONAcute intoxication of fluoroacetamide could damage cardiomyocytes while acetamide could reduce the injury of them, but the injury was reversible. The levels of serum myocardial enzymes could be a usable index for early diagnosis.

Acetamides ; pharmacology ; Alanine Transaminase ; blood ; Animals ; Antidotes ; pharmacology ; Creatine Kinase, MB Form ; blood ; Fluoroacetates ; toxicity ; L-Lactate Dehydrogenase ; blood ; Myocytes, Cardiac ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood

OBJECTIVESulfur mustard (SM) causes various systemic disturbances in human beings. This study aimed to assess paraclinical changes caused by exposure to SM gas in Iranian veterans during the war between Iraq and Iran.

METHODSA literature review was carried out in international and national medical databases including ISI, Medline, Scopus, Iranmedex and Irandoc. Both Farsi and English literature were searched.

RESULTSSearch of the literature yielded 422 medical articles related to SM poisoning. Among them, 30 relevant articles were thoroughly reviewed. The most important reported complications were leukopenia, neutropenia, lymphopenia, eosinophilia, thrombocytopenia, increased bleeding time, positive C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibody (ANA), decreased T helper cells, natural killer cells, IL6, and IL8 levels, elevation of serum immunoglobulins, decreased levels of T3, T4 and cortisol, increased level of adrenocorticotropic hormone (ACTH), proteinuria, hematuria, and elevated liver enzymes. Also, there were some changes in chest assessments.

CONCLUSIONSSM causes profound systemic complications in victims, even years after exposure. The paraclinical changes can be observed in hematology, immune system, biochemistry, hormonal profile and some imaging studies.

Alanine Transaminase ; blood ; Chemical Warfare Agents ; poisoning ; Hormones ; blood ; Humans ; Immune System ; drug effects ; Male ; Mustard Gas ; poisoning ; Myocardial Perfusion Imaging ; Spirometry ; Veterans

OBJECTIVETo screen out effective ingredients of Huangqi Decoction (HQD) on dimethylnitrosamine (DMN) induced liver fibrosis and its assembling actions.

METHODS(1) DMN solution (0. 5%) was peritoneally injected to rats to prepare the liver fibrosis model for 12 times, starting from the 1st day of modeling to the end of the 4th week. Uniform design method with 4-factor 8-level table was used to optimize the proportion of four ingredients from HQD, including astragaloside (AS), astragalus flavonoids (AF), glycyrrhizae acid (GA), and glycyrrhizae flavonoids (GF). Moreover, the changes of hydroxyproline (Hyp) content in the liver issue and the level of alanine aminotransferase (ALT) in serum were observed as screen indices, and the method of regression analysis was used to find out an optimal combination. (2) A further study for comparing and verifying the efficacy of the obtained optimized prescription was conducted by observing the changes of fibrosis pathology, the content of Hyp in the liver tissue and serum enzyme activity after medication.

RESULTSThe optimal proportion of AS and GA was 164:48. Compared with the model group, the content of Hyp in the liver tissue and the levels of ALT, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum decreased significantly, indicating the inhibiting effect of HQD and the AS/GA combination group on hepatic fibrosis formation (P<0.05). The AS/GA combination group was better than AS/GA used alone group in reducing the content of Hyp in the liver tissue and the level of ALT in serum. Furthermore, the AS/GA combination group was better than the HQD group in reducing the level of ALT in serum.

CONCLUSIONSAS and GA were effective ingredients of HQD, and the combination of AS and GA had obvious synergistic effect in reducing liver collagen deposition and decreasing serum ALT activity in DMN-induced liver fibrosis.

Alanine Transaminase ; blood ; Animals ; Dimethylnitrosamine ; adverse effects ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Hydroxyproline ; analysis ; Liver Cirrhosis, Experimental ; blood ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar