Literature DB >> 31471394

Impact of Bevacizumab on Liver Damage After Massive Hepatectomy in Rats.

Hiroki Mori1, Y U Saito2, Shuichi Iwahashi2, Tetsuya Ikemoto2, Satoru Imura2, Yuji Morine2, Mitsuo Shimada2.   

Abstract

BACKGROUND: The aim of this study was to evaluate the impact of pretreatment with bevacizumab on liver damage in a rat model of massive hepatectomy (Hx) model, as a surrogate model of massive Hx for liver metastasis from colorectal cancer.
MATERIALS AND METHODS: Male Wister rats (n=24) were separated into the following two groups: 90% Hx and 90% Hx plus bevacizumab group. Bevacizumab (5 mg/kg) was injected intraperitoneally 7 days before Hx. Samples of blood and remnant liver tissue were obtained 24 hours after hepatectomy and the following parameters were evaluated: Biochemical analysis; liver regeneration rate; survival rate; and real-time polymerase chain reaction for interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfa), matrix metalloproteinase (Mmp) 2 and Mmp9 mRNA. In addition, samples of whole liver tissue were obtained immediately before Hx and real-time polymerase chain reaction was performed for X-box binding protein 1 (Xbp1), activating transcription factor 6 (Atf6), C/EBP homologous protein (Chop), glucose-regulated protein 78 (Grp78) and heat-shock protein 70 (Hsp70), as markers of endoplasmic reticulum stress response.
RESULTS: The levels of transaminases 24 hours after Hx were significantly reduced in the group pretreated with bevacizumab compared to that not pretreated (p<0.05). The liver regeneration rate at 24 hours after Hx was significantly increased in the group pretreated with bevacizumab compared with the group which underwent Hx alone (p<0.05). The survival rate for the group pretreated with bevacizumab tended to be higher than that of the Hx-only group, 72 hours after Hx (p=0.09). The expressions of Il1b, Mmp2 and Mmp9 mRNA 24 hours after Hx in the group pretreated with bevacizumab tended to be lower than that of rats which underwent Hx alone (p=0.11, 0.09 and 0.15, respectively). The expression of Xbp1, Chop, Grp78 and Hsp70 mRNA immediately before Hx in the group pretreated with bevacizumab were significantly higher than the 90% Hx group (p<0.05).
CONCLUSION: Bevacizumab pretreatment had protective effects on liver injury after massive hepatectomy in rats, apparently via the induction of the endoplasmic reticulum stress response, i.e. the so-called unfolded protein response. Copyright
© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Entities:  

Keywords:  Bevacizumab; endoplasmic reticulum stress; massive hepatectomy; preconditioning; unfolded protein response

Mesh:

Substances:

Year:  2019        PMID: 31471394      PMCID: PMC6754989          DOI: 10.21873/invivo.11626

Source DB:  PubMed          Journal:  In Vivo        ISSN: 0258-851X            Impact factor:   2.155


  35 in total

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  1 in total

1.  Bevacizumab Does Not Inhibit the Formation of Liver Vessels and Liver Regeneration Following Major Hepatectomy: A Large Animal Model Study.

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  1 in total

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