AIM: To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS: Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups). RESULTS: Compared to saline injected controls, NF- kappa B activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF- kappa B activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH. CONCLUSION: These data strongly suggest that (1) NF- kappa B p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF- kappa B. In conclusion, NF- kappa B activation is not critically required for the process of liver regeneration after PH.
AIM: To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS:Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups). RESULTS: Compared to saline injected controls, NF- kappa B activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF- kappa B activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH. CONCLUSION: These data strongly suggest that (1) NF- kappa B p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF- kappa B. In conclusion, NF- kappa B activation is not critically required for the process of liver regeneration after PH.
Authors: Y Iimuro; T Nishiura; C Hellerbrand; K E Behrns; R Schoonhoven; J W Grisham; D A Brenner Journal: J Clin Invest Date: 1998-02-15 Impact factor: 14.808