Parenteral Solution of Nutritional Hepatotrophic Factors Improves Regeneration in Thioacetamide-induced Cirrhotic Livers after Partial Hepatectomy

Abstract

Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining liver may be useful for the recovery of these patients. We demonstrated that nutritional hepatotrophic factors (NHF) is an effective regenerative stimulus for cirrhotic livers in rats subjected to partial hepatectomy (PH). The rats with thioacetamide-induced cirrhosis were subjected to PH, and they were divided into 2 groups. One group received intraperitoneal administration of NHF, and the other group received saline solution. After 12 days, biometric data, collagen content, hepatocyte regeneration (proliferation cell nuclear antigen immunochemistry), and profibrotic gene expression (Collagen-a1, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, and transforming growth factor beta 1) were assessed. The results indicated that the rats treated with NHF after PH had an increased liver size, a reduced amount of collagen, and a higher hepatocyte proliferation index compared with the rats that underwent PH alone. In addition, collagen-a1 gene expression was decreased in the NHF-treated rats. Thus, postoperative improvement in the liver morphology following NHF treatment may cause a significant decrease in the risk of liver failure and mortality after hepatic resection.

Stereology shows that damaged liver recovers after protein refeeding

“…The proportion of binucleate to uninucleate hepatocytes was 13% in the control for the undernourished group; increased to 18% in the undernourished group -explained by the 90% increase in the number of binucleate hepatocytes; subsequently reduced to 10.4% in the renourished group explained by the 85% increase in the number of uninucleate hepatocytes; and finally reached 7.7% in the control for the renourished group. Similarly, very recently, it has been demonstrated that the administration of a proteinic parenteral solution of hepatotrophic factors in partially-hepatectomised rats led to a 44.9% rise in the hepatocyte proliferation rate increasing the liver regenerative capacity [35].…”

Histopatologia do desenvolvimento do modelo de cirrose hepática em ratas pela tioacetamida

“…(Banks, 1992 (Brenner, 2009). O modelo que utiliza a TAA é o mais recente (Guerra et al, 2009, Cogliati et al, 2010, Trotta et al, 2013, produz alterações mais próximas às que ocorrem na cirrose humana (Laleman et al 2006) tais como a peroxidação das membranas lipídicas, necrose celular, fibrose e reorganização micronodular do parênquima, proliferação ductular (Sun et al, 2000) e, finalmente, cirrose macronodular (Hakateyama et al, 2002).…”

“…A utilização deste modelo tem como objetivos a compreensão do desenvolvimento da cirrose e suas consequências, além de estratégias para a sua prevenção e tratamento farmacológico alopático ou com extratos vegetais e soluções nutricionais (Low et al, 2004;Nagata et al, 2005;Pinzani et al, 2005;Chen et al, 2006;Laleman et al, 2006Noda et al, 2006Guerra et al, 2009;Furtado et al 2012;Salama et al, 2012;Xie et al, 2012, Trotta et al, 2013.…”

“…Com o uso da tioacetamida por períodos mais longos, as células ovais originam novos ductos biliares de forma importante com rearranjo do parênquima hepático e instalação da cirrose (Trotta et al, 2013).…”

“…Outro fator determinante da instalação da cirrose é o tempo de uso da TAA. Com um protocolo mais conservador e por tempo mais prolongado (150mg/kg de TAA, via IP por 15 semanas), Trotta et al (2013) obtiveram a promoção e perpetuação da cirrose com remodelamento do parênquima e angiogênese em grau importante. Neste caso, a matriz tempo X dose foi eficaz no desenvolvimento da cirrose.…”