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Published on: December 2, 2022
Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver
Petros Ypsilantis1, Maria Lambropoulou, Constantinos Anagnostopoulos
1Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. pipsil@med.duth.gr
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.
Materials And 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.
Insights
Radiofrequency ablation (RFA) of the liver under the Pringle maneuver suppresses hepatocyte regeneration. Mesna administration protects liver cells by reducing inflammation and injury during RFA procedures.
Area of Science:
- Hepatobiliary surgery
- Interventional radiology
- Surgical oncology
Background:
- Radiofrequency ablation (RFA) is a common liver intervention.
- The Pringle maneuver is used to reduce bleeding during liver surgery.
- The impact of combining RFA with the Pringle maneuver on liver regeneration is not fully understood.
Purpose of the Study:
- To test if the Pringle maneuver attenuates liver regeneration after RFA.
- To investigate the protective effects of mesna on liver tissue during RFA and Pringle maneuver.
- To assess the impact on oxidative stress, inflammation, and hepatocyte mitotic activity.
Main Methods:
- Wistar rats underwent liver RFA, RFA with Pringle maneuver, RFA with Pringle and mesna, Pringle maneuver only, or sham operation.
- Liver oxidative state (GSH/GSSG ratio) and NF-κB activity were measured.
- Serum levels of IL-6, TNF-α, AST, and ALT were quantified.
- Histopathology and hepatocyte mitotic activity were assessed at various time points.
Main Results:
- Liver RFA under Pringle maneuver suppressed hepatocyte mitotic activity.
- Mesna administration preserved hepatocyte regeneration and reduced liver injury.
- The Pringle maneuver increased inflammatory markers (IL-6, TNF-α) and NF-κB activation, which were attenuated by mesna.
- Oxidative stress was induced across groups, but mesna mitigated associated tissue damage.
Conclusions:
- Liver RFA performed with the Pringle maneuver significantly suppresses hepatocyte regeneration.
- Prophylactic mesna administration protects the liver by reducing inflammation and injury.
- Mesna preserves regenerative capacity in non-ablated liver parenchyma during combined RFA and Pringle maneuver.
