ABSTRACT
ABSTRACT Background: Partial hepatectomy is a surgical intervention of the liver that can trigger its regenerative process, where the residual lobes deflagrate a compensatory hyperplasia, causing its restoration almost to the original volume. Nevertheless, depending on the extent of liver damage its regeneration might be impaired. The low-power laser has been studied with beneficial results. Aim: To investigate the possible functional and mutagenic damage arising from the use of low-power laser used in liver regeneration after partial hepatectomy. Methods: Fifteen male adult Wistar rats were hepatectomizated in 70% and laser irradiated or not with dose of 70 J/cm2, 650 nm, 100 mW, directly on the remaining liver, during the perioperative period. These animals were divided into four groups: G1 (control, 7 days); G2 (laser, 7 days); G3 (control, 14 days); G4 (laser, 14 days). Were analyzed the liver weight; number of hepatocytes; deposition of collagen fibers; liver function tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, bilirubin and micronucleus test in peripheral blood erythrocyte. Results: The liver weight was greater in G3 and G4 (p=0.001 and p=0.002) compared to other groups. The deposition of collagen fibers in G1 was statistically higher than the other groups (p=0.01). In tests of liver function and micronucleus test was not found significant differences between the studied groups. Conclusion: Low-power laser stimulation did not cause loss of liver function or mutagenic damage.
RESUMO Racional: A hepatectomia parcial é intervenção cirúrgica que pode desencadear processo regenerativo, onde os lobos residuais deflagram resposta de hiperplasia compensatória, ocasionando restauração próxima ao seu volume original. Contudo, dependendo da extensão das lesões hepáticas a regeneração pode ser prejudicada. O laser de baixa potência tem sido pesquisado com resultados benéficos no processo de regeneração hepática. Objetivo: Investigar os possíveis danos funcionais e mutagênicos decorrentes da utilização do laser de baixa potência utilizado na regeneração hepática após hepatectomia parcial. Métodos: Quinze ratos adultos Wistar foram hepatectomizados a 70%, irradiados ou não com laser, dose de 70 J/cm2, 650 nm,100 mW, de forma direta sobre o fígado remanescente, durante o período transoperatório. Os animais foram distribuídos em quatro grupos: G1 (controle, 7 dias); G2 (laser, 7 dias); G3 (controle 14 dias); G4 (laser,14 dias). Foram analisados o peso do fígado; número de hepatócitos; deposição de fibras colágenas; teste de função hepática: alanina aminotransferase, aspartato aminotransferase, fosfatase alcalina, gama glutamiltransferase, bilirrubinas e teste de micronúcleo em eritrócitos. Resultados: O peso do fígado apresentou-se aumentado nos grupos G3 e G4 (p=0,001 e p=0,002) comparados aos demais grupos. A deposição das fibras colágenas no G1 foi estatisticamente maior em relação aos demais grupos (p=0,01). Nos testes de função hepática e teste de micronúcleo não foram encontradas diferenças significativas entre os grupos. Conclusão: O laser de baixa potência não ocasionou perda de função hepática ou dano mutagênico.
Subject(s)
Animals , Male , Rats , Low-Level Light Therapy/adverse effects , Hepatectomy/methods , Liver Regeneration/radiation effects , Rats, Wistar , Liver Regeneration/physiology , Liver Regeneration/genetics , MutationABSTRACT
Generally, extra-cellular-signal-regulated kinase 5 (ERK5) signaling pathway regulates many physiological activities, such as cell proliferation and cell differentiation. However, little is known about how ERK5 signaling pathway composed of 15 paths participates in regulating hepatocyte proliferation during liver regeneration (LR). In this study, to explore the influence ERK5 signaling pathway upon hepatocytes at gene transcription level, rat genome 230 2.0 array was used to detect expression changes of 75 related genes in isolated hepatocytes from rat regenerating liver. Bioinformatics and systems biology methods were applied to analyze the precise role of ERK5 signaling pathway in regulating hepatocyte proliferation during LR. Results showed that 62 genes were contained in the array and 22 genes were significantly changed. It was found that 6 paths were related to hepatocyte proliferation during rat LR. Among them, paths 3, 6 and 13 of ERK5 signaling pathway modulated cell cycle progression by decreasing the negative influence on ERK5 and paths 3, 4, 8 and 9 by reinforcing the positive influence on ERK5. In summary, the study shows that 22 genes and 6 paths of ERK5 signaling pathway participate in regulating proliferation of hepatocytes in rat LR.