PROTEASOME INHIBITOR LACTACYSTIN ABLATES LIVER INJURY INDUCED BY INTESTINAL ISCHAEMIA–REPERFUSION (English)

Clinical and Experimental Pharmacology and Physiology

The aim of the present study was to investigate the role of proteasome in the pathogenesis of liver injury induced by intestinal ischaemia–reperfusion (I/R) and the effect of the proteasome inhibitor lactacystin on neutrophil infiltration, intracellular adhesion molecule (ICAM)‐1 and nuclear factor (NF)‐κB expression in the liver tissues of rats.

Thirty‐two Wistar rats were randomly divided into four groups (n = 8 in each group) as follows: (i) a control, sham‐operated group; (ii) an I/R group subjected to 1 h intestinal ischaemia and 4 h reperfusion; (iii) a group pretreated with 0.2 mg/kg lactacystin 1 h before intestinal I/R; and (iv) a group pretreated with 0.6 mg/kg lactacystin 1 h before intestinal I/R. Liver and intestine histology were observed. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), as well as 20S proteasome activity in circulating white blood cells, were measured. Myeloperoxidase (MPO) activity in liver tissues and the immunohistochemical expression of liver NF‐κB and ICAM‐1 were assayed. In addition, a western blot of liver NF‐κB was performed.

Compared with the sham‐operated control group, liver and intestine injury was induced by intestinal I/R, characterized as histological damage including oedema, haemorrhage and infiltration by inflammatory cells, as well as a significant increase in serum AST (365 ± 121 vs 546 ± 297 IU/L, respectively;P <� 0.05), ALT (65 ± 23 vs 175 ± 54 IU/L, respectively; P <� 0.01) and LDH levels (733 ± 383 vs 1434 ± 890 IU/L, respectively; P <� 0.05). Compared with the control group, MPO activity in the liver tissues increased significantly in the I/R group (2.05 ± 0.69 vs 3.42 ± 1.11 U/g, respectively; P <� 0.05). Strong positive expression of liver ICAM‐1 and NF‐κB p65 was observed.

Compared with the intestinal I/R group, administration of 0.6 mg/kg lactacystin markedly reduced 20S proteasome activity in circulating white blood cells (15.47 ± 4.00 vs 2.07 ± 2.00 pmol 7‐amino‐4‐methylcoumarin (AMC)/s per mg, respectively; P <� 0.01) and ameliorated liver injury, which was demonstrated by decreased levels of serum AST (546 ± 297 vs 367 ± 86 IU/L, respectively;P <� 0.05), ALT (175 ± 54 vs 135 ± 26 IU/L, respectively;P <� 0.05) and LDH (1434 ± 890 vs 742 ± 218 IU/L, respectively; P <� 0.05) and a reduced liver pathological score (2.13 ± 0.64 vs 1.25 ± 0.46, respectively; P <� 0.01). Compared with the intestinal I/R group, MPO activity in liver tissues decreased significantly following lactacystin pretreatment (3.42 ± 1.11vs2.58 ± 0.61 U/g, respectively; P <� 0.05) and the expression of liver NF‐κB and ICAM‐1 was markedly ameliorated.

The present study reveals that the proteasome inhibitor lactacystin ablates liver injury induced by intestinal I/R. One possible mechanism responsible for this effect is the inhibition of enhanced ICAM‐1 and neutrophil infiltration by inhibition of NF‐κB activity. The results suggest the feasibility of using proteasome inhibitor clinically in the treatment of intestinal I/R.

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Table of contents – Volume 34, Issue 11

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

1091
AGE‐RELATED CHANGES IN THE STRUCTURE AND FUNCTION OF SKELETAL MUSCLES
Faulkner, John A / Larkin, Lisa M / Claflin, Dennis R / Brooks, Susan V | 2007
1097
MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION
Sun, Sheng‐Li / Li, Tie‐Jun / Yang, Peng‐Yuan / Qiu, Yan / Rui, Yao‐Cheng | 2007
1102
PROTEASOME INHIBITOR LACTACYSTIN ABLATES LIVER INJURY INDUCED BY INTESTINAL ISCHAEMIA–REPERFUSION
Yao, Ji‐Hong / Li, Ying‐Hua / Wang, Zhen‐Zhen / Zhang, Xue‐Song / Wang, Yu‐Zhu / Yuan, Jin‐Chan / Zhou, Qin / Liu, Ke‐Xin / Tian, Xiao‐Feng | 2007
1109
EFFECTS OF RESVERATROL ON NUMBER AND ACTIVITY OF ENDOTHELIAL PROGENITOR CELLS FROM HUMAN PERIPHERAL BLOOD
Wang, Xiao‐Bin / Huang, Jun / Zou, Jian‐Gang / Su, En‐Ben / Shan, Qi‐Jun / Yang, Zhi‐Jian / Cao, Ke‐Jiang | 2007
1116
FLAVONE INHIBITS VASCULAR CONTRACTION BY DECREASING PHOSPHORYLATION OF THE MYOSIN PHOSPHATASE TARGET SUBUNIT
Jeon, Su Bun / Kim, Gutae / Kim, Jee In / Seok, Young Mi / Kim, Sang‐Hyun / Suk, Kyoungho / Shin, Heung‐Mook / Lee, Young‐Ho / Kim, In Kyeom | 2007
1121
SPINAL a-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID RECEPTORS MAY MEDIATE THE ANALGESIC EFFECTS OF EMULSIFIED HALOGENATED ANAESTHETICS
Hang, L. H. / Shao, D. H. / Yang, Y. H. / Dai, T. J. / Zeng, Y. M. | 2007
1121
SPINAL α‐AMINO‐3‐HYDROXY‐5‐METHYL‐4‐ISOXAZOLEPROPIONIC ACID RECEPTORS MAY MEDIATE THE ANALGESIC EFFECTS OF EMULSIFIED HALOGENATED ANAESTHETICS
Hang, Li‐Hua / Shao, Dong‐Hua / Yang, Ying‐Hong / Dai, Ti‐Jun / Zeng, Yin‐Ming | 2007
1126
S100B LEVELS IN THE CEREBROSPINAL FLUID OF RATS ARE SEX AND ANAESTHETIC DEPENDENT
Vicente, Évelin / Tramontina, Francine / Leite, Marina C / Nardin, Patricia / Silva, Mariane / Karkow, Ana R / Adolf, Rafael / Lucion, Aldo B / Netto, Carlos A / Gottfried, Carmem et al. | 2007
1131
STRONTIUM FRUCTOSE 1,6‐DIPHOSPHATE RESCUES ADENINE‐INDUCED MALE HYPOGONADISM AND UPREGULATES THE TESTICULAR ENDOTHELIN‐1 SYSTEM
Feng, Yu / Zhang, Qi / Dai, De‐Zai / Ying, Han‐Jie / Dai, Yin | 2007
1138
EXPRESSION OF CYP3A ISOFORMS AND P‐GLYCOPROTEIN IN HUMAN STOMACH, JEJUNUM AND ILEUM
Canaparo, Roberto / Finnström, Niklas / Serpe, Loredana / Nordmark, Anna / Muntoni, Elisabetta / Eandi, Mario / Rane, Anders / Zara, Gian Paolo | 2007
1145
DESENSITIZATION OF GUINEA‐PIG TAENIA CAECI SMOOTH MUSCLE INDUCED BY A LOW CONCENTRATION OF CARBACHOL
Hishinuma, Shigeru / Sato, Ryo / Saito, Masaki | 2007
1151
EFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST‐PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERS
Sanaka, Masaki / Yamamoto, Takatsugu / Anjiki, Hajime / Nagasawa, Kunitaka / Kuyama, Yasushi | 2007
1156
ACTIVATION OF PERIPHERAL CHEMORECEPTORS CAUSES POSITIVE INOTROPIC EFFECTS IN A WORKING HEART–BRAINSTEM PREPARATION OF THE RAT
Braga, Valdir A / Zoccal, Daniel B / Soriano, Renato N / Antunes, Vagner R / Paton, Julian F / Machado, Benedito H / Nalivaiko, Eugene | 2007
1160
RESTORATION OF ANTIBIOTIC SUSCEPTIBILITY IN METHICILLIN‐RESISTANT STAPHYLOCOCCUS AUREUS BY TARGETING MECR1 WITH A PHOSPHOROTHIOATE DEOXYRIBOZYME
Hou, Zheng / Meng, Jing‐Ru / Niu, Chao / Wang, Hai‐Fang / Liu, Jie / Hu, Ben‐Quan / Jia, Min / Luo, Xiao‐Xing | 2007
1165
LOW CORONARY DRIVING PRESSURE IS ASSOCIATED WITH SUBENDOCARDIAL REMODELLING AND LEFT VENTRICULAR DYSFUNCTION IN AORTOCAVAL FISTULA
Guido, Maria C / De Carvalho Frimm, Clovis / Koike, Márcia K / Cordeiro, Fernanda F / Moretti, Ana IS / Godoy, Luiz C | 2007
1173
NITRIC OXIDE MODULATES AIR EMBOLISM‐INDUCED LUNG INJURY IN RATS WITH NORMOTENSION AND HYPERTENSION
Liu, Yen Chin / Kao, Shang Jyh / Chuang, I Chun / Chen, Hsing I | 2007
1181
NOVEL EVIDENCE SUGGESTING AN ANTI‐OXIDANT PROPERTY FOR ERYTHROPOIETIN ON VANCOMYCIN‐INDUCED NEPHROTOXICITY IN A RAT MODEL
Cetin, Hasan / Olgar, şeref / Oktem, Faruk / Ciris, Metin / Uz, Efkan / Aslan, Çaǧatay / Ozguner, Fehmi | 2007
1186
ACTIONS OF THE ENDOCANNABINOID TRANSPORT INHIBITOR AM404 IN NEUROPATHIC AND INFLAMMATORY PAIN MODELS
Mitchell, Vanessa A / Greenwood, Ruth / Jayamanne, Angelo / Vaughan, Christopher W | 2007
1191
ANGIOTENSIN II RECEPTORS SUBTYPES MEDIATE DIVERSE GENE EXPRESSION PROFILE IN ADULT HYPERTROPHIC CARDIOMYOCYTES
Zhou, Juan / Xu, Xin / Liu, Jin‐Jun / Lin, Yuan‐Xi / Gao, Guang‐Dao | 2007
1199
DIABETES‐INDUCED CHANGES IN 5‐HYDROXYTRYPTAMINE MODULATION OF VAGALLY INDUCED BRADYCARDIA IN RAT HEART
García, Mónica / Morán, Asunción / Martín, M Luisa / Ortizde Urbina, A Vega / San Román, Luis | 2007
1207
GENOTYPE AND ALLELE FREQUENCIES OF N‐ACETYLTRANSFERASE 2 AND GLUTATHIONE S‐TRANSFERASE IN THE IRANIAN POPULATION
Torkaman‐Boutorabi, Anahita / Hoormand, Mahmood / Naghdi, Naser / Bakhshayesh, Masoomeh / Milanian, Iraj | 2007
1212
EARLY RENAL DENERVATION PREVENTS DEVELOPMENT OF HYPERTENSION IN GROWTH‐RESTRICTED OFFSPRING
Ojeda, Norma B / Johnson, W Russell / Dwyer, Terry M / Alexander, Barbara T | 2007
1217
AMELIORATION OF l‐THYROXINE‐INDUCED HYPERTHYROIDISM BY COUMARIN (1,2‐BENZOPYRONE) IN FEMALE RATS
Panda, Sunanda / Kar, Anand | 2007

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