Comparison of the Apoptotic Effects of Topically Applied Papaverine, Diltiazem, and Nitroprusside to Internal Thoracic Artery.

OBJECTIVE: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. METHODS: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. RESULTS: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. CONCLUSION: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Erythropoietin prevents nitric oxide and cathepsin-mediated neuronal death in focal brain ischemia.

We examined the preventive effect of human recombinant erythropoietin (HrEPO) on nitric oxide (NO)-mediated toxicity to neurons and cysteine protease release into cytoplasm, which is attributed to neuronal death in brain ischemia. Focal cerebral ischemia was induced by permanent occlusion of middle cerebral artery in two sets of rat. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. A group in both set was administered human recombinant erythropoietin (HrEPO). NO content, cathepsins B and L activity increased significantly in the post-ischemic cerebral tissue (p<0.05). HrEPO treatment reduced NO concentration and cathepsin activity to control level (p>0.05). A significant increase in the number of necrotic and apoptotic neurons was observed in the post-ischemic cerebral cortex (p<0.05). HrEPO treatment was markedly lowered both of these (p<0.05). It is concluded that HrEPO prevents neuronal death by protecting neuronal liposomes from NO-mediated toxicity and suppressing the release of cathepsins.

Protective effects of leptin on ischemia/reperfusion injury in rat bladder.

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.

Antioxidant effects of melatonin and coenzyme Q10 on oxidative damage caused by single-dose ochratoxin A in rat kidney.

In the study, the effects of relatively high single-dose of Ochratoxin A (OTA) and the antioxidant effects of Melatonin (Mel) and Coenzyme Q10 (CoQ10) on OTA-induced oxidative damages in rats were investigated. A total of 28 male Sprague-Dawley rats were divided into four groups of 7 rats each: Control, OTA, Mel+OTA and CoQ10+OTA groups. Malondialdehyde (MDA) levels in the plasma and glutathione (GSH) levels in whole blood were measured; kidneys (for histological inspection and for apoptosis detection by TUNEL method) and bone marrow samples (for chromosome aberration and mitotic index) were taken. The rats in the OTA group showed limited degeneration of tubular cells. In some tubules karyomegaly, desquamated cells and vacuolization were observed by light microscopy. Mel and CoQ10 treatment significantly reduced the severity of the lesions. MDA levels of the OTA group were significantly higher than the control, OTA+Mel and OTA+CoQ10 groups, while GSH levels were significantly lower than the control, OTA+Mel and OTA+CoQ10 groups. Higher incidences of apoptotic bodies were observed in the kidneys of the OTA group although OTA administration did not significantly change the incidence of apoptotic bodies when compared to the control and antioxidant administrated groups. Although the percentage of the mitotic index was lowest in the OTA group, no statistical difference was found among the groups. Additionally, OTA had no numerical and structural significant effects on chromosomes. It was observed that single-dose OTA administration caused oxidative damages in rat kidney and Mel or CoQ10 treatment appeared to ameliorate the OTA-induced tissue injuries.

The effect of doxorubicin on rats that received toxic and carcinogenic benzo(a)pyrene.

Benzo(a)pyrene (B(a)P) is a polycyclic aromatic hydrocarbon with carcinogenic and toxic effects. Doxorubicin is a DNA-interacting drug widely used in chemotherapy. In the present study we investigated the effects of doxorubicin on rats that received benzo(a)pyrene. Sprague-Dawley male rats, 3-4 months old, were divided into 5 groups (n=9 per group). Group 1 (controls) received normal saline intraperitoneally (i.p.) and intragastrically (i.g.), Group 2 (controls) similarly received corn oil i.p. and i.g., Group 3 received corn oil soluble benzo(a)pyrene (10mg/kg b.wt every 10 days for 40 days), Group 4 received doxorubicin (4 mg i.p. on 3 consecutive days), Group 5 received doxorubicin for 3 days (as in group 4) followed by benzo(a)pyrene as in group 3. After twenty-four hours urine samples were collected, heart blood, liver and kidney tissue samples were obtained. Biochemical data were evaluated on urine and blood; liver and kidney tissue samples were investigated histologically. Uric acid, urine creatinine, creatine clearance, urea nitrogen, serum creatinine values, serum glutamic oxaloacetic transaminase (SGOT, AST), serum glutamic pyruvic transaminase (SGPT, ALT), alkaline phosphatase (ALP, AP), superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were significantly different in the 3rd group compared with control groups. Most of the parameters group 5 were statistically similar to control values. Histological appearance of the liver and the kidney tissue samples supported the improvement in the 5th group. The result of our study indicated that liver and kidney functions impaired with benzo(a)pyrene may be partially restored by doxorubicin.

Protective effect of zinc on cyclophosphamide-induced hematoxicity and urotoxicity.

Cyclophosphamide (CP) is widely used for the treatment of neoplastic diseases; however, its toxicity causes dose-limiting side effects. Zinc (Zn) is an essential trace element and has important biological functions that control many cell processes including DNA synthesis, normal growth, reproduction, fetal development, bone formation, and wound healing. Therefore, the toxicity of CP and the possible protective effect of Zn on blood cells, bone marrow, and bladder of rat were investigated in this study. Intraperitoneal administration of 50, 100, or 150 mg/kg CP for 3 days caused, in a dose-dependent manner, reductions in the number of leukocytes, thrombocytes, and bone marrow nucleated cells and a serious urotoxicity. To explore whether CP-induced damages could be prevented by Zn, other groups of rats were pretreated with 4 or 8 mg/kg ZnCl2 intraperitoneally for 3 days then challenged with respective doses of CP plus ZnCl2 on day 4 for three more days. The results indicated that treatment of rats with Zn could dose-dependently alleviate CP-induced toxicities on blood cells, bone marrow cells, and urinary bladder. We suggest that Zn could be a potentially effective drug in the prevention of CP-related hematoxicity and urotoxicity.

The effect of paclitaxel on rats following benzo(a)pyrene treatment.

OBJECTIVE: To observe the effects of paclitaxel on rats that received benzo(a)pyrene. METHODS: In this study, 45 male Sprague-Dawley rats aged 2-month-old were used, which were housed at the Medical Biology Department of Eskisehir Osmangazi University, Eskisehir, Turkey in 2006. Urine, blood, liver, and kidney tissue samples of Sprague Dawley rats treated with benzo(a)pyrene and paclitaxel were examined in our study. Biochemical data were evaluated on urine and blood samples, and liver and kidney tissue samples were investigated by light microscopy. RESULTS: Superoxide dismutase, catalase activities, and malondialdehyde values in the group which received benzo(a)pyrene were significantly different than the control, and most of these parameters came close to control values in the group that received paclitaxel following benzo(a)pyrene application. Histological appearances of the samples of all rats also supported the biochemical results. CONCLUSION: The present study indicated that liver and kidney structures damaged by benzo(a)pyrene may be restored by paclitaxel.

The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p < 0.05). Dexanabinol treatment reduced NO concentration and cathepsin activity to the control level (p > 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p < 0.05). However, dexanabinol treatment lowered both of these (p < 0.05). We conclude that dexanabinol might be a useful agent for the treatment of stroke patients.

Effects of carvacrol on defects of ischemia-reperfusion in the rat liver.

Many plants found in nature have been used to treat various illnesses. One such plant is oregano (Kekik in Turkish). Health beneficial effects of carvacrol obtained from oregano oil have been shown scientifically. We have investigated the comparative effects of carvacrol in the liver of rats subjected to ischemia-reperfusion defect, with silymarin. To test the effects we formed four groups using male Wistar albino rats. Group I was control. The other three groups of animals were administered 60min prior to surgical operation single doses of physiological serum, carvacrol and silymarin, respectively. Group II, III and IV animal were subjected to 45min long liver ischemia and 60min reperfusion. Blood and tissue samples were collected for biochemical and histological analysis following the test. AST and ALT values obtained after biochemical analysis of the serums showed statistically significant difference in group II than the other three groups. A statistical evaluation of the serum AST levels among the groups II, III and IV showed that both groups III and IV which had no difference in between were significantly different in a positive way from group II (p<0.001). As to the serum ALT levels, difference between group II and group III (p<0.001) and group II and group IV (p<0.01) was found significant. No statistical difference was observed in groups I, III and IV for GSH, MDA and CAT levels of the liver. A statistical evaluation of the GSH level in group III and group IV was found to be significantly different from group II (p<0.001) without any difference between them. A similar evaluation for MDA and CAT levels among the revealed no difference between group III and group IV, however, group II showed difference with group II and group IV (p<0.05). Histological findings were in harmony with the biochemical results. We conclude that carvacrol protects the liver against defects caused by ischemia and reperfusion, and carvacrol is not hepatotoxic at the applied dosage.

Effects of carvacrol upon the liver of rats undergoing partial hepatectomy.

The present study aims to investigate the possible effects of carvacrol obtained from origanum oil upon the regenerative feature of the liver subsequent to partial hepatectomy in rats. Male Wistar Albino rats, weighing 230+/-30g, were divided into three experiment groups. Group I (n=8) were used as sham operation group. Group II (n=8) were applied saline solution and hepatectomy. Carvacrol and hepatectomy (73mg/kg) were applied to Group III (n=8). One dose of test material was injected 1h before 68% partial hepatectomy. At the end of the experiments, blood and organs were removed. The liver regeneration rate of the rats was calculated measuring the weights of their liver before and after the hepatectomy. Hematoxylin and eosin, interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) treatments were applied to liver sections. Aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IL-6 levels were determined in serum samples. The liver regeneration, mitotic index and PCNA index increased significantly in rats of Group III over the Group II at the 72nd hour after partial hepatectomy. Histological evaluations were also similar with these results of PCNA and mitotic indexes. In AST, ALT, TNF-alpha and IL-6 levels, there was no statistically significant difference. According to these results, it is concluded that carvacrol increases the liver regeneration rate.

Protective role of melatonin and coenzyme Q10 in ochratoxin A toxicity in rat liver and kidney.

Melatonin (MEL) and coenzyme Q10 (CoQ10) both display antioxidant and free radical scavenger properties. In the present study, the effect of MEL and CoQ10 on the oxidative stress and fibrosis induced by ochratoxin A (OTA) administration in rats was investigated. Rats were divided into five equal groups, each consisting of seven rats: (1) controls; (2) OTA-treated rats (289 microg/kg/day); (3) OTA+MEL-treated rats (289 microg/kg/day OTA + 10 mg/kg/day MEL); and (4) OTA+CoQ10-treated rats (289 microg/kg/day OTA + 1 mg/100 g/day body weight (bw) CoQ10). After 4 weeks of treatment, the level of malondialdehyde (MDA), glutathione peroxidase (GPx), and hydroxyproline (Hyp) were measured in the homogenates of liver and kidney. In the OTA-treated group, the levels of MDA and Hyp in both liver and kidney were significantly increased when compared with the levels of control, whereas GPx activities decreased. In OTA+MEL-treated rats, the levels of MDA and Hyp in both liver and kidney were significantly decreased when compared with the levels of OTA-treated rats; however; GPX activities increased. In the OTA+CoQ10-treated group, the levels of MDA and Hyp were decreased when compared with the levels of OTA-treated rats, whereas GPx activities increased. In the OTA+CoQ10-treated group, the levels of MDA, Hyp, and GPx were not significantly changed in kidney when compared with OTA-treated group. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and fibrosis both liver and kidney. Although CoQ10 has protective effect against OTA toxicity in liver tissue, it has no effect in kidney tissue.

Preventive effects of Ginkgo biloba extract on ischemia-reperfusion injury in rat bladder.

AIMS: The aim of this experimental study was to evaluate the effects of Ginkgo biloba (EGb 761) on ischemia-reperfusion (I-R) injury in the rat bladder. METHODS: A bladder I-R injury was induced by abdominal aorta occlusion by ischemia for 30 min, followed by 45 min reperfusion in rats. The rats were divided into four groups of 7 rats each; the control, I-R, and I-R groups were pretreated intraperitoneally with 50 or 100 mg/kg G. biloba 60 min before ischemia induction. Contractile responses to carbachol through isolated organ bath studies were recorded, histological sections were evaluated by light microscopy, and TUNEL staining was performed for the evaluation of apoptosis. RESULTS: In the I-R group, the contractile responses of the bladder strips were lower than those of the control group (p < 0.01-0.001) and were restored by pretreatment with 100 mg/kg G. biloba (p < 0.05-0.001). Decreased polymorphonuclear leukocyte infiltration was detected in the G. biloba pretreatment groups when compared to the I-R group during histological evaluation. The ratio of TUNEL-positive nuclei was 1.84% in the I-R group, whereas it was decreased in both of the G. biloba pretreatment groups (p < 0.01, p < 0.01). CONCLUSION: Our data indicated that G. biloba has a preventive effect on I-R injury in rat urinary bladder.

Neuroprotective effects of L-carnitine and vitamin E alone or in combination against ischemia-reperfusion injury in rats.

BACKGROUND: Neurological injury because of transient cerebral ischemia is a potential complication of cardiovascular surgery. In this study, the neuroprotective effects of L-carnitine, vitamin E, and the combination of these agents on ischemia/reperfusion (I/R) injury were determined in a rat model of transient global cerebral I/R. METHODS: Rats were pretreated with L-carnitine (100 mg/kg, i.v.) and vitamin E (50 mg/kg, i. v.), alone or in combination and then subjected to cerebral I/R induced by a four-vessel-occlusion technique for a duration of 15 min followed by 15 min of reperfusion. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were measured in the cerebral tissues. Histopathological examinations were also carried out under light and electron microscopy. RESULTS: The results showed that I/R elevated MDA levels, which were accompanied by a reduction in SOD activities and GSH levels. Surviving neurons was markedly decreased in CA1 and CA3 subfield of hippocampus in I/R animals. L-carnitine, vitamin E, and their combination restored MDA levels and SOD activities, with a tendency to increase surviving neurons in CA1 and CA3 subfield. Combined treatment of L-carnitine and vitamin E had better GSH levels than individual treatment of these agents. CONCLUSIONS: The results suggest that L-carnitine has a potent neuroprotective effect against cerebral-I/R-induced injury in rat brain that is comparable to that of vitamin E. However, the combined use of L-carnitine and vitamin E does not further protect from neuronal injury, although it provides an increase in GSH levels.

Mast cell stabilizator and antioxidant effects of epidermal growth factor (EGF) on gastric mucosal injury induced by ethanol in rats.

The role of epidermal growth factor (EGF), a polypeptide containing 53 amino acids, on protection and repair of ethanol-induced gastric mucosal injury was investigated in rats. In addition, the effects of EGF on the gastric damage were evaluated histopathologically. We used 48 Spraque-Dawley rats which were divided into [corrected] three groups as control rats, ethanol treated rats and ethanol+EGF treated rats. The ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. EGF (100 microg/kg) was given by intragastric gavage 30 min before the administration of ethanol. We studied histopathological evaluation and the histochemical heterogeneity of mast cells and its degree of degranulation. Besides, gastric tissue malondialdehyde (MDA), protein sulfhydryl groups (SH), and protein carbonyl levels were measured. EGF treatment stabilized mast cells degranulation and had lower polymorphonuclear leukocytes (PMNL) infiltration, ulcer index, histamine, and MDA; protein carbonyl levels were also lower, compared to the non-treated animals. EGF exerts a protective effect on gastric mucosa to ethanol-induced gastric injury probably through antioxidant and mast cell stabilizing mechanism.

The effect of trimetazidine on liver regeneration after partial hepatectomy under hepatic blood inflow occlusion.

BACKGROUND/AIMS: It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion. METHODOLOGY: Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight). RESULTS: Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2. CONCLUSIONS: Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.

Intestinal ischemia-reperfusion impairs liver regeneration after partial hepatectomy in rats.

BACKGROUND/AIMS: The deleterious effects of intestinal ischemia-reperfusion on liver are realized, but its effect on the regenerative capacity of the liver has not been studied. Our aim in this study was to determine the effect of intestinal ischemia-reperfusion on liver regeneration. METHODOLOGY: Sprague-Dawley rats were randomly divided into six groups; two sham-operated, two hepatectomy, and two hepatectomy with intestinal ischemia-reperfusion groups. To create intestinal ischemia-reperfusion, the superior mesenteric artery and collateral arteries supplying the small intestine were occluded for 20 minutes. Partial hepatectomy was performed during the period of ischemia. Ischemia-reperfusion injury in the mucosal layer of the small intestine was scored in light microscopy. Liver regeneration parameters (proliferating cell nuclear antigen labeling index for hepatocytes and liver regeneration rate), and serum levels of aspartate aminotransferase and alanine aminotransferase were studied on day 1 or 4 after operation. RESULTS: Mucosal injury score was high in the hepatectomy with intestinal ischemia-reperfusion groups. Liver regeneration rate and proliferating cell nuclear antigen labeling index were less in these groups than the hepatectomy groups on day 1 and 4. There were no differences in the serum levels of aspartate aminotransferase and alanine aminotransferase between hepatectomy and hepatectomy with intestinal ischemia-reperfusion groups. The mortality rate was higher in the hepatectomy with intestinal ischemia-reperfusion groups than the other groups. CONCLUSIONS: Ischemia and reperfusion of the small intestine impaired liver regeneration with high mortality after partial hepatectomy in the rats.

Increased intraabdominal pressure impairs liver regeneration after partial hepatectomy in rats.

BACKGROUND: There are many experimental studies showing that increased intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and portal venous congestion. But, there is no study evaluating the effect of increased IAP on liver regeneration. It is well known that acute liver ischemia and portal venous congestion impair liver regeneration. We, therefore, aimed to determine the effect of increased IAP on liver regeneration in this study. METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of 12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy with increased IAP groups. Mitotic index, proliferating cell nuclear antigen (PCNA)-labeling index, and liver regeneration rate as liver regeneration parameters were studied on day 1 or on day 4 after operation. Additionally, serum aspartate transaminase (AST) level and histopathological changes in intestinal mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had significantly higher serum AST levels than the sham-operated group on day 1. Serum AST level was found to be significantly higher in the hepatectomy with increased IAP group than in the other groups on day 4. Intestinal mucosal injury was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic index and PCNA-labeling index were markedly higher in all hepatectomy with/without increased IAP groups than in the sham-operated groups. However, together with liver regeneration rate, both indices were significantly less in the hepatectomy with increased IAP groups than in the hepatectomy groups both on day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24 h impaired liver regeneration after partial hepatectomy in rats.