To study the mechanism of endotoxin-induced hepatocellular injury in rats, a single dose of endotoxin, 15mg/kg, was injected intraperitoneally with or without dexamethasone pretreatment. Studies included light microscopic, histochemical, and electron microscopic observations with concomitant assay of free acid phosphatase activity of liver homogenateg. The results showed an increase of acid phosphatase activity as early as 30 minutes after the injection of endotoxin, and by light microscopy random focal necrosis of liver cells at 1 hour and fibrin thrombi formation in sinusoids especially within the area of necrosis at 3 hours. However, ultrastructural alteration was noted as early as 5 minutes after the injection of endotoxin characterized by marked dilatation of RER. The degree of necrosis, fibrin thrombus formation, and the elevation of free acid phosphatase activity in the liver homogenates seemed to parallel each other suggesting a possible interrelationship among these phenomena. However, the ultrastructnral changes of the hepatocytes were present far ahead of the appearance of fibrin thrombi formation. Therefore, the causal relationship of the fibrin thrombi to liver cell injury appeared unlikely. Despite the increase of free acid phosphatase activity in liver homogenates, no demonstrable structural disruption of lysosomal membrane was noted. In view of the prominent changes of RER 5 minutes after the endotoxin administration, the primary injurious effect of endotoxin affects the membrane system of all organelles including the lysosomal membrane, leading to the leakage of lysosomal enzymes into the cytoplasmic sap. Dexamethasone pretreatment alleviated necrosis and markedly inhibited fibrin thrombus formation, and the mechanism of this effect is considered to be a stabilizing effect of glucocorticoid upon membrane systems.
Acid Phosphatase/metabolism ; Animal ; Endotoxins* ; Injections, Intraperitoneal ; Liver/enzymology ; Liver/pathology* ; Liver Diseases/chemically induced ; Liver Diseases/metabolism ; Liver Diseases/pathology* ; Male ; Necrosis ; Rats

OBJECTIVETo explore the hepatic injury induced by CCl4in SD rat.

METHOD40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination.

RESULT19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group.

CONCLUSIONCCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats.

Animals ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Cysts ; chemically induced ; pathology ; Disease Models, Animal ; Female ; Liver ; pathology ; Liver Cirrhosis ; chemically induced ; pathology ; Liver Diseases ; pathology ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Precancerous Conditions ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley ; Sex Factors

A 3-year-old Thoroughbred filly was referred to the Equine Hospital, Korea Racing Association for evaluation of hematuria, inappetite, weight loss and depression. From 25 days prior to admission, the horse was treated for right carpal lameness with 20 mg intramuscular administration of triamcinolone acetonide per day for consecutive 10 days by a local veterinarian. Clinical and laboratory findings included vaginal hyperemia, flare in bladder wall, neutrophilia, lymphopenia, polyuria, polydipsia and laminitis in the end. High activities of aspartate transaminase and gamma glutamyltransferase and high concentration of total bilirubin indicated hepatopathy. Further hematology, serum biochemistry and urinalysis did not reveal any abnormalities. Medical history, physical and clinicopathologic findings suggest that the laminitis and hepatopathy in this horse were most likely induced by repeated administration of exogenous corticosteroid. However, guarded prognosis of treating laminitis undermined the benefit of improvement of hematuria following electroacupuncture stimulation. The combined stimulation of kidney related acupoints (Shen Peng, Shen Shu), lumber related acupoints (Yao Qian, Yao Zhong) and associate acupoints (Guan Yuan Shu, Bai Hui) at 5Hz, 1-2V, for 40 minutes was of value in the treatment of hematuria. This case shows that horses under steroids may exhibit laminitis and steroid hepatopathy. Early recognition and good management of laminitis are important in the limitation of complications.
Animals ; Electroacupuncture/veterinary ; Female ; Foot Diseases/chemically induced/pathology/*veterinary ; Forelimb/pathology ; Glucocorticoids/*adverse effects/therapeutic use ; Hoof and Claw/pathology ; Horse Diseases/*chemically induced/pathology ; Horses ; Lameness, Animal/*chemically induced/drug therapy ; Liver Diseases/chemically induced/*veterinary ; Triamcinolone Acetonide/*adverse effects/therapeutic use

We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson's disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury.
Acute Disease ; Adrenergic alpha-Antagonists/*adverse effects ; Dysuria/pathology ; Humans ; Liver Diseases/*chemically induced/pathology ; Liver Function Tests ; Male ; Middle Aged ; Prostatic Hyperplasia/drug therapy ; Quinazolines/*adverse effects

Alcohols ; Animals ; Disease Models, Animal ; Female ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases, Alcoholic ; metabolism ; pathology ; Proto-Oncogene Proteins c-sis ; biosynthesis ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the antagonism effects of green tea (GT) against microcystin LR (MC-LR) induced hepatotoxicity and nephrotoxicity in mice.

METHODSAll 40 male mice were randomly divided into four groups. Mice in group III and IV were pretreated with green tea for free drink at doses of 2 g/L and 12 g/L prior to MC-LR intoxication, for consecutively 18 days. The toxin treatment mice were administered continually intraperitoneal injections of MC-LR at a dose of 10 microg x kg(-1) x d(-1) bw from day 6th till sacrifice, continually 13 days. Mice were sacrificed and immediately subjected to necropsy, and the body weight, relative organ weight, serum biochemical parameters, antioxidant enzyme levels (SOD and GSH), lipid peroxidation products (MDA) and histopathology were systematically evaluated.

RESULTSMC-LR exposure led to increase the oxidative stress and organ injury was significantly observed through biochemical parameters and microscopic evaluation. However, high dose of GT pretreatment caused a significant elevation in serum GSH and SOD levels, and a decrease of serum MDA level as compared with MC-LR control. The mean values of GSH and SOD activities were separately 467.29 mg/L and 139.22 U/ml in group IV. Subsequently, GT pretreatment obviously diminished the serum ALT, AST and Cr activities. Those pathological damages in liver and kidney, were to a certain extent, lessened in GT pretreatment mice in correlation with the biochemical parameters.

CONCLUSIONGT might elevate antioxidant defense system, clean up free radicals, lessen oxidative damages and protect liver and kidney against MC-LR induced toxicity.

Animals ; Antioxidants ; pharmacology ; Chemical and Drug Induced Liver Injury ; Free Radicals ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Microcystins ; toxicity ; Oxidative Stress ; Tea

Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA-treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries.
Alanine Transaminase/blood ; Alkaline Phosphatase/blood ; Animals ; Bilirubin/blood ; *Drug-Induced Liver Injury ; Griseofulvin/*toxicity ; Liver Diseases/*drug therapy/pathology ; Mice ; Mice, Inbred ICR ; Microscopy, Electron ; Porphobilinogen/urine ; Porphyrias/*chemically induced/*drug therapy/pathology ; Ursodeoxycholic Acid/*therapeutic use

OBJECTIVETo evaluate the role of adiponectin in regulating tumor necrosis factor alpha (TNF alpha) production and preventing fulminant autoimmunological damage of hepatocytes following concanavalin A (Con A) injection into mice.

METHODSThree days after recombinant plasmids pAA-neo-mAd were injected into the mice via the tail veins, Con A was injected into the mice. Mice transfected with empty pAA-neo vector served as controls. The serum levels of alanine aminotransferase (ALT), TNF alpha and adiponectin were detected, and histological examination of livers was carried out at different time points after the Con A injection. All results were subjected to statistical analyses.

RESULTSHistological examinations showed that the damage in livers of mice with high serum adiponectin levels was milder than that of the controls. The serum levels of ALT and TNF alpha were both lower than those of the controls (P less than 0.01, respectively). Statistical analyses showed the serum levels of ALT was negatively related to the levels of adiponectin in the sera (r=-0.5034).

CONCLUSIONAdiponectin is effective in protecting hepatocytes from Con A-induced immunological injury. The mechanism of this protective effect may be caused by inhibiting the synthesis and/or release of TNF alpha.

Adiponectin ; blood ; pharmacology ; Alanine Transaminase ; blood ; Animals ; Concanavalin A ; adverse effects ; Female ; Immune System Diseases ; chemically induced ; pathology ; prevention & control ; Liver ; drug effects ; pathology ; Liver Diseases ; pathology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo explore the effect of Dogwood fruits on tonifying kidney-yang.

METHODThe effect of the water extract of Dogwood fruits on rats model of kidney-yang deficiency with the hydrocortisone was observed.

RESULTThe water extract of Dogwood fruits could make normal the liver weight, and mitigate hepatocyte pathologic changes, increase the heptocellular levels of RNA and hepatin, and decrease the malondialdehyde (MDA) in rats model of kidney-yang deficiency. It could also make the viscera quotiety return to normal way and increase the levels of RNA in the interstitial cells of testicle in rats model of kidney-yang deficiency.

CONCLUSIONWater extract of Dogwood fruits can protect and improve the functions of the liver and testicle in rats model of kidney-yang deficiency.

Animals ; Cornus ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fruit ; chemistry ; Hydrocortisone ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Liver Glycogen ; metabolism ; Male ; Malondialdehyde ; metabolism ; Plants, Medicinal ; chemistry ; RNA ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Testis ; metabolism ; pathology ; Yang Deficiency ; chemically induced ; metabolism ; pathology

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.
Vomiting/chemically induced ; Treatment Outcome ; Survival Analysis ; Neoplasm Recurrence, Local ; Nausea/chemically induced ; Middle Aged ; Male ; Magnetic Resonance Imaging ; Liver Diseases/chemically induced ; Leukopenia/chemically induced ; Humans ; Glioma/*drug therapy/radiotherapy/surgery ; Female ; Drug Administration Schedule ; Dacarbazine/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Combined Modality Therapy ; Brain Neoplasms/*drug therapy/radiotherapy/surgery ; Brain/drug effects/pathology ; Antineoplastic Agents, Alkylating/administration & dosage/adverse effects/therapeutic use ; Adult ; Adolescent ; Administration, Oral