Protective effects of N-acetylcysteine on the liver of brain-dead Ba-Ma mini pig.

Abstract

OBJECTIVE:

To investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of N-acetylcysteine (NAC) on hepatic function and on nuclear factor (NF)-kappaB mRNA and protein expression.

METHODS:

Fifteen Ba-Ma mini pigs were equally divided into three groups at random: brain-dead group (group B), NAC-pretreated group (group N), and control group (group C). A brain-death model was established by increasing intracranial pressure in a modified, slow, and intermittent way. At 6, 12, and 24 hours after the initial brain death, we determined the levels of serum aspartate transferase (AST), alanine transferase (ALT), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. At the same times, hepatic tissue samples were obtained to assess morphological changes in hepatic tissues and the expression of NF-kappaB mRNA and protein was detected by reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively.

RESULTS:

The levels of AST and ALT in groups B and N began to increase at 12 hours after brain death; the levels among group N were lower than those in group B (P < .05). The levels of serum IL-1beta, IL-6, and TNF-alpha in group B and group N began to increase gradually at 6 hours after brain death; those of group B were all significantly greater than those among group N at each time (P < .05). The mRNA and protein levels of NF-kappaB among groups B and N began to increase at 6 hours after brain death; however, those of group B were all significantly higher than those of group N (P < .05). Light and electron microscopy showed only mild edema of liver cells in group N. At 12 hours after brain death, mitochondrial swelling and edema in liver cells were observed among group B, with more severe morphological lesions in this group than group N.

CONCLUSIONS:

NAC inhibited the degree of NF-kappaB mRNA transcription and its protein translation, decreasing the release of inflammatory factors, and thus alleviating hepatic injury during brain death.

• Authors: J Li, S Zhang, Y Wu, W Guo, Y Zhang, W Zhai
• Journal: Transplantation proceedings (Transplant Proc) 2010 Jan-Feb Vol. 42 Issue 1 Pg. 195-9 ISSN: 1873-2623 [Electronic] United States
• PMID: 20172312 (Publication Type: Journal Article)

Chemical References

• DNA Primers
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Aspartate Aminotransferases
• Alanine Transaminase
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Brain Death
• DNA Primers
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Liver (drug effects, metabolism, pathology)
• NF-kappa B (drug effects, genetics)
• RNA, Messenger (drug effects, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Swine
• Swine, Miniature
• Tumor Necrosis Factor-alpha (blood)