Inhibitory Effect of Vitamin E Administration on the Progression of Liver Regeneration Induced by Partial Hepatectomy in Rats

Abstract

SUMMARY:We have proposed that controlled peroxidative modifications of membranes could be playing a role in the early steps of liver regeneration. Hence, lipid peroxidation (LP) was modified in vivo by treatment with vitamin E in rats subjected to partial hepatectomy (PH), and its influence on liver regeneration was evaluated. Our results, using several methods to monitor LP, indicate that vitamin E administration promoted a decreased LP rate in liver subcellular membranes. Vitamin E drastically diminished cytosolic LP, shifting earlier increased LP in plasma membranes, and promoted a higher increase of nuclear LP in animals subjected to PH. Pretreatment with vitamin E induced a striking reduction of liver mass recovery and nuclear bromodeoxyuridine labeling (clearly shown at 24 hours after surgery), as well as promoted a decreased expression of cyclin D1 and of the proliferating cell nuclear antigen after PH. These effects seem to lead to a decreased mitotic index at 48 hours after PH. Vitamin E pretreatment also diminished PH-induced hypoglycemia but elevated serum bilirubin level, which was not observed in PH animals without vitamin treatment. In conclusion, an enhanced but controlled LP seems to play a critical role during the early phases of liver regeneration. Decreasing magnitude or time course of the PH-promoted enhanced LP (at early post-PH stages) by in vivo treatment with vitamin E could promote an early termination of preparative cell events, which lead to the replicative phase, during PH-promoted liver proliferation. The latter could have a significant implication in the antitumorigenic effect ascribed to the treatment with vitamin E. (Lab Invest 2003, 83:1669 -1679.

The response of liver lipid peroxidative and antioxidant defense systems of protein undernourished rats to liver regeneration

“…We report here, for the first time, that partially hepatectomised protein undernourished rats exhibit increased lipid peroxidation when compared with shamoperated protein-undernourished rats, suggesting increased ROS production following cell proliferation in the regenerating liver of PU rats. This observation in PU rats is consistent with the observation that PH induce an increase in LP in partially hepatectomised well-fed rats (19,20).…”

Comparing the regenerative effects of silymarin and apricot on liver regeneration after partial hepatectomy in rats

“…It has been reported by some researchers that several factors improving and promoting the liver regeneration and some of them are as follows; prostaglandin E2 enhances the proliferation of hepatocytes by increasing intracellular cyclic AMP [30], nitric oxide, a flow-dependent factor is a trigger to initiate the regeneration process [31], antioxidant treatment with vitamin E [32], carvacrol [33], prostaglandin E1 [34], resveratrol and melatonin [35], Triiodothyronine (T3) [36], beneficial effects of clinoptilolite [37] and SDOA [4].…”

O estresse oxidativo na regeneração hepática em ratos

“…A oferta de GSH exógena, no entanto, influi negativamente sobre a evolução da regeneração hepática 23 . Mais ainda: os antioxidantes, de um modo geral, inibem a regeneração hepática 6,14,24 . Mesmo sob regeneração, os estudos são basicamente unânimes em mostrar que a maioria, senão todas, das funções hepáticas necessárias à homeostase orgânica, incluindo sín-tese de albumina, de fatores de coagulação e de bile, manutenção da glicemia e da atividade do ciclo da uréia, permanecem preservadas 21,25 .…”

“…A peroxidação lipídica tem sido implicada como um dos fatores na enorme gama de influenciadores no fenômeno da regeneração 5,6,7 . A glutationa (GSH), considerada como um dos componentes mais importantes do sistema defensivo antioxidante das células 8 está presente em humanos, animais, plantas e bactérias aeróbias em altas concentrações 9 e é abundante (3 a 10 mM) tanto no citoplasma, como no núcleo e na mitocôndria, tornando alta a probabilidade que espécies reativas de oxigê-nio (ERO) sejam eliminadas pela reação com GSH antes que possam iniciar os efeitos danosos.…”

“…A HP, gerando o fenômeno da regeneração hepática, ao se constituir em um trauma per se, induz um estresse oxidativo que, conforme sugerem as pesquisas, se constitui em fator incluso na enorme gama de fatores indutores, determinantes e influenciadores da regeneração 5,6,7,14 .…”