Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver.
BACKGROUND
The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration.


METHODS
Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens.


RESULTS
Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h.


CONCLUSIONS
Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.
Ypsilantis
Petros
P
Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. pipsil@med.duth.gr
Lambropoulou
Maria
M
Anagnostopoulos
Constantinos
C
Tentes
Ioannis
I
Tsigalou
Christina
C
Pitiakoudis
Michail
M
Kortsaris
Alexandros
A
Papadopoulos
Nikolaos
N
Simopoulos
Constantinos
C
D000818:Animals; D017115:Catheter Ablation; D049109:Cell Proliferation / Q000187:drug effects; D006499:Hepatic Artery / Q000503:physiopathology*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000502:physiology / Q000601:surgery*; D008115:Liver Regeneration / Q000187:drug effects*; D015080:Mesna / Q000494:pharmacology*; D023421:Models, Animal; D016328:NF-kappa B / Q000097:blood; D011169:Portal Vein / Q000503:physiopathology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013525:Surgical Instruments; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D016328:NF-kappa B; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000637:Transaminases; D015080:Mesna