ENHANCERS OF LIVER REGENERATION IN ONCOLOGICAL SURGERY

Abstract INTRODUCTION Chemotherapy hinders liver function and probably its regenerating capacity, forcing to delay it after surgery. Our objective has been to verify this effect in an experimental model and to see if a hepatotrophic agent can prevent it. MATERIAL AND METHODS Four groups of 6 WAG/RijHsd rats (males, 3-4 months) were submitted to ligation of the portal branch to the left lateral and left paramedian lobes. They were sacrificed 36 h later to quantify the percentage of liver corresponding to the ligated lobes (weight), the number of hepatocyte’s nuclei (nº/100 µm2) and their mean size (µm2). One group received no treatment (control); another folic acid (2.5 mg/kg ip, during surgery); other 5-Fluorouracil (5-FU 50 mg/kg ip 48 h before); and the fourth received folic&5-FU. RESULTS The animals treated with folic acid showed a greater number of hepatocyte’s nuclei (24.4 ± 2.77 vs 15.2 ± 1.51) and their mean size was also greater (121 ± 2.34 vs 111 ± 1.8). However, the reduction in weight of the ligated parenchyma was less than in control group (33.4 ± 1.08 vs 29.5 ± 1.08). 5-FU did not modify the number of nuclei (15.6 ± 18.4), although they were smaller in size (104 ± 1.7). The addition of folic acid to 5-FU increased the number of nuclei (21.7 ± 2.8) and normalized their size (111 ± 3.2). CONCLUSIONS 5-FU exerts a depressant effect on livers regeneration, and folic acid overcomes it. Thus, folic acid could allow early application of chemotherapy without affecting liver regeneration.

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Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Cancers ◽

10.3390/cancers14020371 ◽

2022 ◽

Vol 14 (2) ◽

pp. 371

Author(s):

Jorge Gutiérrez Sáenz de Santa María ◽

Borja Herrero de la Parte ◽

Gaizka Gutiérrez-Sánchez ◽

Inmaculada Ruiz Montesinos ◽

Sira Iturrizaga Correcher ◽

...

Keyword(s):

Liver Function ◽

Portal Vein ◽

Liver Regeneration ◽

Folinic Acid ◽

Hepatic Metastases ◽

Future Liver Remnant ◽

Control Group ◽

Portal Vein Ligation ◽

Nuclear Area ◽

Liver Remnant

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

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Liver regeneration with l-glutamine supplemented diet: experimental study in rats

Revista do Colégio Brasileiro de Cirurgiões ◽

10.1590/s0100-69912014000200008 ◽

2014 ◽

Vol 41 (2) ◽

pp. 117-121 ◽

Cited By ~ 9

Author(s):

Cibelle Ribeiro Magalhães ◽

Osvaldo Malafaia ◽

Orlando Jorge Martins Torres ◽

Luciane Bugmann Moreira ◽

Silvia Carmen da Silva Gonçalves Tefil ◽

...

Keyword(s):

Liver Function ◽

Liver Regeneration ◽

Liver Weight ◽

Male Rats ◽

Control Group ◽

Standard Diet ◽

Weight Changes ◽

Indirect Bilirubin ◽

And Control ◽

Cell Mitosis

OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and without supplementation of L-glutamine through liver weight changes, laboratory parameters and histological study.METHODS: 36 male rats were divided into two groups: glutamine group and control group. Each group was subdivided into three subgroups, with death in 24h, 72h and seven days. The glutamine group received water and standard diet supplemented with L-glutamine, and the control recieved 0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and indirect bilirubin and albumin) and analysis of cell mitosis by hematoxylin-eosin.RESULTS: In both groups there was liver regeneration by weight gain. Gamma-GT increased significantly in the control group (p < 0.05); albumin increased in the glutamine group. The other indicators of liver function showed no significant differences. Histological analysis at 72h showed a higher number of mitoses in the glutamine group, with no differences in other subgroups.CONCLUSION: Diet supplementation with L glutamine is beneficial for liver regeneration.

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Supportive Hepatocyte Transplantation after Partial Hepatectomy Enhances Liver Regeneration in a Preclinical Pig Model

European Surgical Research ◽

10.1159/000516690 ◽

2021 ◽

pp. 1-10

Author(s):

Felix Oldhafer ◽

Eva-Maria Wittauer ◽

Oliver Beetz ◽

Clara A. Weigle ◽

Lion Sieg ◽

...

Keyword(s):

Liver Function ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Pig Model ◽

Hepatocyte Transplantation ◽

Factor Vii ◽

Control Group ◽

Group 3 ◽

Group 2 ◽

Group 1

Background: Hepatocyte transplantation (HTx) is regarded as a potential treatment modality for various liver diseases including acute liver failure. We developed a preclinical pig model to evaluate if HTx could safely support recovery from liver function impairment after partial hepatectomy. Methods: Pigs underwent partial hepatectomy with reduction of the liver volume by 50% to induce a transient but significant impairment of liver function. Thereafter, 2 protocols for HTx were evaluated and compared to a control group receiving liver resection only (group 1, n = 5). Portal pressure-controlled HTx was performed either immediately after surgery (group 2, n = 6) or 3 days postoperatively (group 3, n = 5). In all cases, liver regeneration was monitored by conventional laboratory tests and the novel noninvasive maximum liver function capacity (LiMAx) test with a follow-up of 4 weeks. Results: Partial hepatectomy significantly impaired liver function according to conventional liver function tests as well as LiMAx in all groups. A mean of 4.10 ± 1.1 × 108 and 3.82 ± 0.7 × 108 hepatocytes were transplanted in groups 2 and 3, respectively. All animals remained stable with respect to vital parameters during and after HTx. The animals in group 2 showed enhanced liver regeneration as observed by mean postoperative LiMAx values (621.5 vs. 331.3 μg/kg/h on postoperative day 7; p < 0.001) whereas HTx in group 3 led to a significant increase in mean liver-specific coagulation factor VII (112.2 vs. 54.0% on postoperative day 7; p = 0.003) compared to controls (group 1), respectively. In both experimental groups, thrombotic material was observed in the portal veins and pulmonary arteries on histology, despite the absence of clinical symptoms. Conclusion: HTx can be performed safely and effectively immediately after a partial (50%) hepatectomy as well as 3 days postoperatively, with comparable results regarding the enhancement of liver function and regeneration.

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Effects of topical gel formulation of Ficus carica latex on cutaneous leishmaniasis induced by Leishmania major in BALB/c mice

BMC Research Notes ◽

10.1186/s13104-021-05614-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Ali Pouryousef ◽

Erfan Eslami ◽

Sepehr Shahriarirad ◽

Sina Zoghi ◽

Mehdi Emami ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Murine Model ◽

Leishmania Major ◽

Considerable Effect ◽

Ficus Carica ◽

Control Group ◽

Topical Gel ◽

The Third ◽

Mean Size ◽

The Mean

Abstract Objectives The current study aimed to evaluate the effects of Ficus carica latex on the treatment of cutaneous leishmaniasis (CL), induced by Leishmania major. A 5% topical gel with F. carica latex was prepared. BALB/c mice were infected by inoculation of amastigotes form of L. major. Thirty BALB/c mice were divided into five groups, where the first group was treated daily, the second group twice per day, and the third group every other day with the 5% topical gel, for 3 weeks. The sizes of the lesions were measured before and during the course of treatment. Results Although the mean size of lesions in the mice group treated with the 5% F. carica gel, especially in the group receiving daily treatment, was less than the mean size of the lesions in the control group, yet, the differences was not statistically significant (p > 0.05). The findings of the current study demonstrated that the 5% F. carica latex with a 3-week course of treatment had no considerable effect in recovery or control of CL induced by L. major in the murine model. Using higher concentration of F. carica latex and with longer treatment lengths may increase its efficacy in the treatment of CL.

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SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i5.13237 ◽

2016 ◽

Vol 9 (5) ◽

pp. 197

Author(s):

Meilinah Hidayat ◽

Sijani Prahastuti ◽

Estherolita Dewi ◽

Dewi Safitri ◽

Siti Farah Rahmawati ◽

...

Keyword(s):

Liver Function ◽

Toxicity Test ◽

Low Dose ◽

Ethanol Extract ◽

Good Effect ◽

Control Group ◽

High Dose ◽

Subchronic Toxicity ◽

Treatment Groups ◽

Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

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Folic Acid Affects Iron Status in Female Rats with Deficiency of These Micronutrients

Biological Trace Element Research ◽

10.1007/s12011-019-01888-z ◽

2019 ◽

Vol 195 (2) ◽

pp. 551-558 ◽

Cited By ~ 1

Author(s):

Joanna Suliburska ◽

Katarzyna Skrypnik ◽

Agata Chmurzyńska

Keyword(s):

Folic Acid ◽

Iron Status ◽

Iron Concentration ◽

Folic Acid Supplementation ◽

Female Rats ◽

Control Group ◽

Standard Diet ◽

Study Group ◽

Female Wistar Rats ◽

Iron And Folic Acid

Abstract Although simultaneous supplementation with iron and folic acid is justified, the potential interactions between these micronutrients are unknown. The aim of this study was to determine the effects of oral iron and folic acid, administered together or separately, on iron concentration in tissues in rats with a deficiency of both these micronutrients. In the first stage of the experiment (28 days), 150 8-week-old female Wistar rats were randomly assigned to a control group (C; n = 30) fed the standard diet and to a study group (n = 120) fed a diet deficit in iron and folate. The study group was then randomly divided to four groups: D group fed a deficit diet, FE group fed a deficit diet with iron gluconate, the FOL group fed a deficit diet with folate acid, and the FEFOL group fed a deficit diet with iron gluconate and folate acid. After 2, 10, and 21 days of supplementation, ten animals from each group were killed. Morphological parameters were measured in whole blood. Iron concentration was assayed in serum, liver, spleen, pancreas, heart, and kidneys. Folic acid supplementation more significantly decreased iron concentrations in the pancreas and spleen than in the D group after 10 and 21 days of supplementation. Moreover, the combination of iron with folic acid markedly decreased iron levels in the liver and spleen, in comparison with iron alone, after 10 and 21 days of the experiment. In conclusion, folic acid affects iron status in female rats deficient in these micronutrients in moderate and long-term supplementation.

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Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00733.2013 ◽

2014 ◽

Vol 306 (2) ◽

pp. H286-H290 ◽

Cited By ~ 4

Author(s):

Calvin K. Chan ◽

Song Yan Liao ◽

Yue Lin Zhang ◽

Aimin Xu ◽

Hung Fat Tse ◽

...

Keyword(s):

Area Under The Curve ◽

Treated Group ◽

Control Group ◽

Protective Effects ◽

Treatment Control ◽

Porcine Coronary Artery ◽

Endogenous Histamine ◽

Coronary Endothelium ◽

Treatment Control Group

In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg−1·day−1) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.

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