Erythropoietin promotes hepatic regeneration after extended liver resection in rats

Background and Aim:  It has been proven in various animal studies that recombinant human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as hepatic, tissue from ischemia, and promotes regeneration of adult central nervous system neurons. To date, no data are available as to whether rHuEPO has the ability to stimulate liver regeneration after liver resection.
Methods:  Rats undergoing 70% or 90% hepatectomy received an intraportalvenous administration (i.p.) of rHuEPO prior to resection or a subcutaneous injection (s.c.) for 3 days postoperatively, control animals were treated with surgery and saline injection only. Regeneration capacity of remnant livers was studied over 7 days by histology and immunohistochemistry (Ki-67, proliferating cell nuclear antigen [PCNA]). Polymerase chain reaction was carried out to measure transforming growth factor β (TGF-β), hypoxia induced factor (HIF), signal transducing activator 3 and vascular endothelial growth factor.
Results:  Ten-day survival in rats undergoing 90% hepatectomy significantly increased in i.p.-pretreated animals. After 70% hepatectomy the mitotic index was significantly increased in both rHuEPO-treated groups. These data were confirmed by PCNA and Ki-67 expression, which was significantly increased in the treated groups 24 h and 2 days after liver resection. TGF-β and HIF mRNA both were upregulated in control animals 3 h after surgery.
Conclusion:  rHuEPO effectively increased liver regeneration in rats after 70% liver resection and enhanced survival after 90% hepatectomy. Thus, rHuEPO may increase the regenerative capacity after major hepatectomy.     

Liver regeneration is impaired by FK778 in partially hepatectomized rats, while supplemental uridine restores both liver growth and hepatocyte proliferation

Aim:  The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model.
Methods:  Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline ( n  = 28), uridine ( n  = 16), FK778 alone ( n  = 28) or in combination with uridine ( n  = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage.
Results:  In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h ( P  < 0.05) after the PH. In addition, morphological analysis showed confluent central lobular necrosis at 72 h in four of seven animals. Uridine supplementation restored PI, LBR and the de Ritis ratio in FK778-treated animals and no confluent necroses were observed.
Conclusion:  FK778 is antihepatotrophic as well as antiproliferative during rat liver regeneration. Both liver growth and hepatocyte proliferation are completely restored by supplementation with uridine. In addition, supplemental uridine markedly reduces the severity of morphological abnormalities consistent with FK778 toxicity.     

Effect of vascular endothelial growth factor on hepatic regenerative activity following partial hepatectomy in rats.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is an angiogenic factor with a growth-promoting effect that is thought to be restricted to vascular endothelial cells. Its essential role during liver regeneration has yet to be determined. The aim of this study was to document the effect of exogenous VEGF administration on liver regeneration in rats undergoing submaximal hepatic resections. METHODS: Adult male Sprague-Dawley rats (n = 4/group) undergoing 30% partial hepatectomy were administered 200 ng VEGF165 intravenously and were sacrificed at 24, 36, and 48 h postoperatively. Liver regeneration was monitored by measuring the restituted liver mass, proliferating cell nuclear antigen (PCNA) immunostaining, and hepatic PCNA protein by Western blot. RESULTS: Changes in restituted liver mass 48 h postsurgery were more prominent, but did not differ statistically between VEGF-treated and control rats (47% vs. 29%; p<0.06). Nevertheless, PCNA immunostaining showed increased labeling index of hepatocytes, apparent at 36 and 48 h after partial hepatectomy (38% vs. 18% [p<0.041 and 42% vs. 11% [p<0.021], respectively). Hepatic PCNA proteins measured by Western blot showed a 3-fold increase in VEGF-treated rats 48 h postsurgery compared with controls (p<0.01). CONCLUSION: Exogenous VEGF administration early after partial hepatectomy stimulates liver regeneration in rats. Whether or not VEGF165 is a direct mitogen for hepatocytes remains to be determined.     

Effects of octreotide on liver regeneration and tumour growth in the regenerating liver

The ability of the liver to regenerate following resection is remarkable. However, there is evidence to suggest that tumour growth within the regenerating liver is significantly increased. As octreotide (a synthetic analogue of somatostatin) inhibits the growth and development of hepatic tumour in rats, we have investigated its effects on liver regeneration, liver blood flow, hepatic reticuloendothelial system activity and tumour growth in the rat following partial hepatectomy (PH). Octreotide significantly inhibited liver regeneration in the rat 1 and 2 weeks following PH when compared with controls (regeneration index: 1.0 and 1.14 cf. 1.14 and 1.4, respectively). There was no significant difference in hepatic arterial or portal venous blood flow following PH in control or octreotide-treated rats. However, portal pressure was significantly reduced in octreotide-treated rats. Hepatic reticuloendothelial system activity was significantly increased in octreotide-treated rats compared with control animals 1 and 2 weeks after hepatectomy (uptake of radiolabelled technetium-99m albumin colloid: 2.2 and 3.9 cf. 1.6 and 1.9). The growth of both HSN (fibrosarcoma) and K12-Tr (colonic adenocarcinoma) cells in the regenerating liver was significantly decreased by octreotide treatment compared with controls (median percentage hepatic replacement: HSN control 71.3%, Octreotide 8.4%, K12-Tr Control 38.3%, Octreotide 4.5%). The results of the present study demonstrate that octreotide inhibits both liver regeneration and tumour growth following PH, possibly via a similar mechanism.     

Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway

The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased ability of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudocapillarization of old liver and improved hepatosinusoidal blood flow. After hepatectomy, the open fenestrae were associated with a restored attachment of platelets to endothelium and the initiation of a normal regenerative response, including the up-regulation of essential growth mediators and serotonin receptors. In turn, hepatocyte proliferation recovered along with regain of liver volume and animal survival. DOI operates through the release of VEGF, and its effects could be blocked with anti-VEGF antibodies both in vitro and in vivo. These results suggest that pseudocapillarization in the aged acts as a barrier to liver regeneration. DOI breaks this restraint through an endothelium-dependent mechanism driven by VEGF. This pathway highlights a target for reversing the age-associated decline in the capacity of the liver to regenerate.     

Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to regeneration.RESULTS The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.     

Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90% hepatectomy in the rat

BACKGROUNDLiver reduction is the main curative treatment for primary liver cancer, but its use remains limited as liver regeneration requires a minimum of 30% functional parenchyma. AIMTo study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy (90%) and postoperative glucose infusions.METHODSPost-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%. The animals received a post-operative glucose infusion and were randomly assigned to two groups: One to investigate the survival rate and the other for biochemical analyses. Animals that underwent laparotomy or 70% hepatectomy were used as controls. Blood and liver samples were collected on postoperative days 1 to 7. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, and western blotting. RESULTSPostoperative mortality after major resection reached 20% and 55% in the first 24 h and 48 h, respectively, with an overall total of 70% 7 d after surgery. No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers, but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities. Liver regeneration started properly, as early events initiating cell proliferation occurred within the first 3 h, and the G1 to S transition was detected in less than 12 h. However, a rise in p27 (Kip1) followed by p21 (Waf1/Cip1) cell cycle inhibitor levels led to a delayed S phase progression and mitosis. Overall, liver regeneration in rats with a 90% hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis. CONCLUSIONThis work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.     

Paradoxical effects of glucose feeding on liver regeneration and survival after partial hepatectomy

Although glucose is regularly administered to patients after partial hepatic resection, its contribution to survival and/or liver regeneration is unclear. To examine this question fed and anesthetized rats underwent 68% or 90% hepatectomy and received either oral 20% glucose solution or tap water (controls) ad lib for 24 h. Survival was compared by life table analysis and the regeneration response measured by 3H-thymidine uptake into liver deoxyribonucleic acid (DNA). Profound hypoglycemia (60 +/- 8 mg/dl) following 90% hepatectomy in controls was corrected by glucose feeding (99 +/- 25 mg/dl) and survival was enhanced (75 +/- 0.09% vs. 42 +/- 0.1%, p less than 0.01). No deaths occurred in the 68% hepatectomy groups wherein untreated hypoglycemia was not as severe (106 +/- 6 mg/dl). However, after 68% hepatectomy glucose adversely affected the regeneration response. We conclude that glucose feeding corrected the life threatening hypoglycemia following 90% hepatectomy. Prophylactic glucose administration after 68% hepatectomy reduced the liver regeneration response. Selective glucose administration to prevent lethal hypoglycemia may provide optimal survival and conditions for regeneration.     

Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model

BACKGROUND AND AIM: The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH). METHODS: db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR. RESULTS: Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase. CONCLUSIONS: In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.     

Simultaneous transfer of vascular endothelial growth factor and hepatocyte growth factor genes effectively promotes liver regeneration after hepatectomy in cirrhotic rats

BACKGROUND/AIMS: Liver regeneration in a cirrhotic liver is unsatisfactory. In the course of liver regeneration, non-parenchymal cells such as sinusoidal endothelial cells as well as hepatocytes increase in number while the liver structure and physiological functions are maintained. The aim of this study was to examine whether sufficient liver regeneration could be obtained by the simultaneous, preoperative injection of recombinant adenoviral vectors encoding human vascular endothelial growth factor (VEGF), a potent mitogen for sinusoidal endothelial cells, (pAxCAVEGF) and rat hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, (pAxCAHGF) in 70% hepatectomized cirrhotic rats. METHODOLOGY: Forty-eight hours before 70% hepatectomy, dimethylnitrosamine-induced cirrhotic rats were infused intravenously with pAxCAVEGF or with pAxCAVEGF and pAxCAHGF, or with a control virus encoding Escherichia coli beta-galactosidase (pAxCALacZ). RESULTS: Strong VEGF mRNA expressions were shown in the livers of VEGF and VEGF/HGF-treated animals. The plasma HGF concentrations in the VEGF/HGF-treated rats were elevated compared with the other groups. Proliferating cell nuclear antigen immunostaining showed increased labeling indices of hepatocytes in the VEGF/HGF-treated rats at 24 and 48 h after hepatectomy. PCNA labeling indices of SECs were increased in the VEGF and VEGF/HGF-treated rats compared with the control animals at 24 and 48 h after hepatectomy. Moreover, the hepatic regeneration rate after hepatectomy was significantly augmented by the VEGF and VEGF/HGF treatment. CONCLUSIONS: Simultaneous preoperative injection of recombinant adenoviral vectors encoding VEGF and HGF effectively stimulates liver regeneration in cirrhotic rats.     

Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis

AIM To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis(NASH) model influences surgical outcome.METHODS For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl_4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy(PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH.RESULTS In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups(P 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase(AST) levels and total bilirubin(T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups(AST: P 0.05, T-Bil: P 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group(P 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group(P 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis.CONCLUSION The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.     

Simultaneous extensive resection of the liver and the pancreas in dogs

Mortality, morbidity, liver function and regeneration were evaluated in dogs that had undergone simultaneous major resection of the liver and the pancreas. The 10-week survival rate was only 25% in the dogs that underwent 70% hepatectomy with more than 92% pancreatectomy, and many of them died of liver failure. Longterm survival was observed in more than 60% of the dogs after 70% hepatectomy with less than 92% pancreatectomy or after 40% hepatectomy with more than 92% pancreatectomy. The liver regeneration rate was reduced with the extent of the pancreatectomy, and the reduction was remarkable especially when more than 92% of the pancreas was resected. The frequency of diabetes was reduced when the pancreatectomy was combined with hepatectomy. Hyperlipemia and fatty liver were noted in all the dogs of the group that underwent more than 92% pancreatectomy alone. They were observed also in the postoperative diabetic groups but not in non-diabetic groups. The postoperative recovery of hepatic function and liver regeneration were delayed after simultaneous hepatectomypancreatectomy. Also, postoperative carbohydrate and lipid metabolism was better maintained in the hepatectomypancreatectomy groups than in the pancreatectomy-alone groups.     

Multivariate analysis of liver regenerative capacity after hepatectomy in humans

Many factors affect liver regeneration after partial hepatectomy; however, those factors that are essential for regulation of liver regeneration in humans are not known. Using multiple regression analysis we conducted a study to determine essential factors involved in the speed of liver regeneration after hepatectomy. The subjects were 59 patients who underwent hepatic resection between January 1980 and December 1991. A regression equation for predicting regeneration speed (Y; cm³/day) during the 1st postoperative month was obtained by stepwise forward multiple regression analysis, using 11 explanatory parameters (Xi). The regeneration speed and the resection ratio (%; indicating the magnitude of resection) were calculated based on a computed tomography (CT) scan volumetric study. The degree of liver fibrosis, expressed as the fibrotic index (%), was morphometrically determined in Azan-Mallory stained sections. Of the 11 explanatory parameters, the resection ratio and the fibrotic index had a significant simple correlation with Y. The following regression equation was obtained: Y (cm³/day)=?1.1+3.7 × resection ratio ?5.4 × alkaline phosphatase ?3.7 × fibrotic index +1.2 × total bilirubin ?2.6 × glutamic pyruvic transaminase (multiple correlation coefficient, 0.82). We found that the extent of resection and the degree of fibrosis, as well as alkaline phosphatase, total bilirubin, and glutamic pyruvic transaminase, contributed to the speed of regeneration after partial hepatectomy.     

Effect of Acute Ethanol Exposure on Hepatic Stimulator Substance (HSS) Levels During Liver Regeneration: Protective Function of HSS

Ethanol administration in rats induces liver damage and suppression of liver regeneration. To further understand the underlying mechanism, we investigated the effects of ethanol on hepatic stimulator substance (HSS) levels during liver regeneration caused by partial hepatectomy. The hepatotrophic action of HSS to ethanol-treated partially hepatectomized rats was also examined. Rats received repetitive ethanol or saline doses beginning 1 hr prior to 70% partial hepatectomy (PH), and the animals were killed at 16, 24, 32, 40, 48, and 60 hr after PH. Our results showed that ethanol inhibited hepatic regenerative capacity and prolonged liver regenerative process. HSS biological activity in ethanol-administered rats peaked at 48 hr after PH, in contrast to saline-treated ones where activity peaked at 24 hr. Additionally, exogenous HSS administration to ethanol-treated partially hepatectomized rats increased liver proliferating capacity and suppressed the elevation of serum ALT activity. These results showed that ethanol modifies the time course of HSS biological activity during the regenerating process. The observed suppression of HSS activity at 24 hr after PH was in relation with a reduction of DNA synthesis. Exogenous administration of HSS to ethanol-treated partially hepatectomized rats restored DNA synthesis and ameliorated serum AST levels, indicating that HSS could be used in the treatment of ethanol-induced hepatic failures.     

Exogenous melatonin protects small‐for‐size liver grafts by promoting monocyte infiltration and releases interleukin‐6

Defective regeneration of small‐for‐size (SFS ) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT ) has protective effects on hepatic ischemia‐reperfusion injury (IRI ), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR +PH group: 60 minutes liver ischemia (IR ) plus 2/3 hepatectomy (PH ); (II ) IR +exPH group: 60 minutes liver IR plus extended hepatectomy (exPH ) associated with the SFS syndrome; (III ) SFS ‐LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle‐treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL ) 6, IL 10, and tumor necrosis factor‐α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR +PH group. MLT ‐induced IL 6 significantly improved hepatic microcirculation and survival in the IR +exPH model. In the SFS ‐LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL 6/GP 130‐STAT 3 signaling. In IL 6 ^?/? mice, MLT failed to promote liver recovery, which could be restored through recombinant IL 6. In the IR +exPH and SFS ‐LT groups, inhibition of the IL 6 co‐receptor GP 130 through SC 144 abolished the beneficial effects of MLT . MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte‐released IL 6 and downstream IL 6/GP 130‐STAT 3 signaling.     

Significance of morphological alteration by portal vein branch ligation in endotoxin-induced liver injury after partial hepatectomy.

BACKGROUND: Regenerating liver after partial hepatectomy (PH) is susceptible to endotoxin. This study was conducted to investigate how morphological alteration by preoperative portal vein branch ligation (PVL) affects endotoxin-induced liver injury after PH. METHODS: Male Sprague-Dawley rats were divided into a PVL group undergoing left PVL and into a non-PVL group receiving a sham operation. Seven days later, animals in both groups were subjected to PH (the left lateral, median and caudate lobes). Lipopolysaccharide (LPS) was intravenously administered to both groups 2 days after PH. RESULTS: A significant increase in hepatocyte and sinusoidal endothelial cell proliferation assessed by Ki-67 immunostaining reached a peak at day 2 and 3 after PVL, respectively, in accordance with the changes in plasma interleukin-6 concentrations after PVL. The proliferation response of these cells after PH was observed in both groups, showing a significantly weaker response in the PVL group. The sinusoidal width after PH was significantly reduced in the non-PVL group when compared with that in the PVL group. LPS administration induced a marked elevation of plasma tumour necrosis factor-alpha levels in the non-PVL group compared with the PVL group. PVL before PH significantly attenuated endotoxin-induced functional and structural liver damage with greater hepatic polymorphonuclear leucocyte infiltration and microcirculatory derangement, resulting in an improvement in the 7-day survival rate. CONCLUSIONS: Morphological alteration by PVL is of great advantage in preventing the development of endotoxin-induced liver injury in the regeneration process after PH.     

Enhancement of Liver Regeneration by the Association of Hyptis pectinata with Laser Therapy

Since new molecules that normally would accelerate regeneration can also be potentialized by light, the use of new substances combined with laser therapy seems to be a natural type of experiment. Therefore, the purpose of this study was to assess the effects of Hyptis pectinata leaves on liver regeneration after partial hepatectomy (PH) associated with laser therapy. Twenty-four rats were divided into four groups—PH(control), PHL (laser therapy), PH200 (200 mg/kg of Hyptis pectinata), and PHL200 (200 mg/kg of the plant and laser)—which were submitted to 67% hepatectomy. Laser treatment consisted of focusing the light on the remaining liver after hepatectomy. The data analyzed were serum levels of aminotransferases, liver regeneration, and mitochondrial function. Group PH200 showed a statistically significant decrease in AST levels, and PHL200 disclosed an augmentation in ALT levels. The liver regeneration index was significantly increased in group PHL200. Concerning liver mitochondrial respiratory assay, groups PH200 and PHL200 showed lower state 3 levels than groups PH and PHL. Group PHL showed an increase in state 4 levels and a reduction in membrane potential and RCR. The present study shows that the association of the aqueous extract of Hyptis pectinata leaves at 200 mg/kg with intraoperative laser therapy can stimulate liver regeneration and cause a reduction in liver mitochondrial respiratory function without altering its phosphorylative activity.