Biomedical subjects

C L Liu

Publications and source records attributed to C L Liu.

At least 55 records · Page 3Linked to original sources

PubMed2001

Increased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke.

Epidemiological evidence suggests that smoking is a major cause of human lung cancer. However, the mechanism by which cigarette smoke induces the cancer remains unestablished. To evaluate the effects of cigarette smoke on the expression of inducible nitric oxide synthase (iNOS), nuclear protooncogenes and related mitogen-activated protein kinases (MAPKs) in rat lung tissue, a histopathological study of the effects of gas-phase cigarette smoke on rat lung tissue were carried out. The terminal bronchioles were found to be infiltrated predominantly by lymphocytes in the peribronchiolar region and a mild to moderate degree of emphysema was noted in the alveolar spaces. The terminal bronchioles also showed marked lipid peroxidation, dilatation, and peribronchiolar fibrosis. Immunohistochemical evaluation showed that the expression of iNOS, NF-kappa B, MAPKs (MEK1, ERK2), phosphotyrosine protein and c-fos was increased in the terminal bronchioles but protein kinase C (PKC), MEKK-1, c-jun, p38 and c-myc showed no change. These results provide evidence to suggest that exposure to cigarette smoke results in oxidant stress which leads to the stimulation of iNOS and c-fos together with the induction of protein tyrosine phosphorylation and MEK1/ERK2 which in turn may promote lung pathogenesis.

Animals↗

PubMed2001

Biliary complications during liver resection.

Biliary complications after hepatectomy may lead to sepsis, liver failure, and death. Measures to detect biliary injury after liver transection may reduce such morbidity. The aim of this study was to investigate the trend of biliary complications after hepatectomy during the last 10 years and assess the efficacy of intraoperative measures (methylene blue test, cholangiography, fibrin glue application) for reducing postoperative biliary complications. This is a retrospective study of 616 consecutive patients who underwent hepatectomy in our institution from January 1989 to September 1998. The study period was divided into the first 5 years and the second 5 years for comparison. The hospital mortality rate was 6%. It was significantly reduced during the second 5-year period (3.3% vs. 10.6%; p = 0.0002). The postoperative biliary leakage rate was 5.5% and was also reduced during the second 5-year period (3.5% vs. 9.8%; p = 0.004). Postresection methylene blue tests were performed more frequently during the second 5-year period than the first (63% vs. 28%; p = 0.0001). The postoperative biliary leakage rate was reduced by the methylene blue test (3.6% vs. 7.3%; p < 0.05) but not by application of fibrin glue (7.2% vs. 4.2%) or postresection cholangiography. However, among the 60 patients with a positive methylene blue test, postoperative biliary leakage still occurred in 10% of them after the leakage sites were sutured. In conclusion, the biliary complication rate is decreasing. Only the postresection methylene blue test, but not postresection cholangiography or application of fibrin glue, helps to reduce the postoperative biliary leakage rate.

Adult↗

PubMed2001

Endoscopic stenting for malignant biliary obstruction.

Use of endoscopic stents to manage patients with malignant obstructive jaundice is a well accepted measure. Interpretation of the results of endoscopic stenting must be made with reference to the level of the bile duct obstruction. Results were generally unsatisfactory for hilar lesions, especially when the intrahepatic ducts were segregated into multiple isolated systems. After deployment, stent dysfunction due to clogging by biliary sludge is apparently an inevitable process for the conventional plastic stent. Considerable efforts had been made to prolong the stent patency by changing its physical configuration, coating the inner lumen, and the choice of material but with little success. The development of a self-expandable metal stent is a major advance, but the benefits derived from a larger stent lumen are compromised by the initial expense and the tumor ingrowth through the wires for all models available commercially. Current data failed to substantiate the value of routine preoperative biliary decompression, as there is no reduction in the morbidity and mortality rates after surgery. Although biased patient selection may have resulted in the negative observations made, repeated clinical trials should probably focus on patients with distal bile duct tumors who are preparing for a major pancreatic resection. As a definitive palliative measure, endoscopic stenting is a more cost-effective option than surgery for patients with limited life expectancy based on data regarding plastic stents. The recommendations are evolving however, as there is progressive refinement of laparoscopic surgery techniques and designs of endoscopic stents.

Cholestasis, Extrahepatic↗

PubMed2001

Stress analysis of the disc adjacent to interbody fusion in lumbar spine.

After anterior interbody fusion in the lumbar spine, the accelerated degeneration of the disc adjacent to the fusion levels was clinically observed. To understand the stress distribution of the adjacent disc, this study created a finite element model of the lumbar spine from L1-L5 vertebral body. The fusion model modified from the intact model was used to simulate the anterior interbody fusion. Various loading conditions, which included flexion, extension, lateral bending, and torsion, were applied to the finite element model to study the corresponding stress distribution. From the finite element model calculation, at a lower fusion site or more fusion levels, the stress of the disc adjacent to interbody fusion increased more than upper fusion site or single fusion level under flexion, torsion and lateral bending. Larger stress increase was estimated at the upper disc adjacent to interbody fusion than the lower disc adjacent to interbody fusion. In stress distribution, the upper disc adjacent to interbody fusion had a little alteration under torsion.

Finite Element Analysis↗

PubMed2001

Detection of choledocholithiasis by EUS in acute pancreatitis: a prospective evaluation in 100 consecutive patients.

BACKGROUND: ERCP is the standard for detection of choledocholithiasis in patients with acute biliary pancreatitis, and, if performed early, ERCP decreases morbidity. However, there are procedure-related complications. The aim of the present prospective study was to evaluate the ability of EUS to detect choledocholithiasis in patients presenting with acute pancreatitis. METHODS: The study group comprised 100 consecutive patients who presented with acute pancreatitis. EUS, and immediately thereafter, ERCP were performed by separate blinded examiners within 24 hours of admission. The diagnostic accuracy of EUS in identifying gallbladder stones was compared with that of transcutaneous US. The diagnostic accuracy of EUS in detecting choledocholithiasis was then compared with that of US and ERCP based on the results of endoscopic instrumentation of the bile duct after sphincterotomy. RESULTS: EUS was more sensitive than US in detecting gallbladder stones (100% vs. 84%, p < 0.005). The sensitivities of ERCP and EUS for choledocholithiasis were both 97%, and the overall accuracies were 96% and 98%, respectively, with no significant difference. EUS detected the absence of choledocholithiasis in 65 of 66 patients (specificity = 98%). Endosonographic examination was successful in all patients, whereas ERCP was unsuccessful in 5 patients (p > 0.05). Post-endoscopic sphincterotomy bleeding developed in 4 patients; there was no EUS-related morbidity (p > 0.05). CONCLUSION: EUS is more sensitive than US in detecting biliary stones in patients with acute pancreatitis. It is as accurate as ERCP in detecting choledocholithiasis. EUS can be used to select patients with acute pancreatitis who require therapeutic ERCP, thus avoiding diagnostic ERCP and its associated potential for complications in the majority of patients.

Acute Disease↗

PubMed2001

Liver transplantation in Asian patients with chronic hepatitis B using lamivudine prophylaxis.

OBJECTIVE: To report the results of liver transplantation in 31 Asian patients with chronic hepatitis B using lamivudine prophylaxis in an open-label study. SUMMARY BACKGROUND DATA: Chronic hepatitis B is a prevalent cause of end-stage liver disease in Asia, but the results of liver transplantation in these patients are poor. METHODS: Thirty-one Asian patients with chronic hepatitis B underwent liver transplantation using lamivudine prophylaxis (100 mg daily). Twenty-three (74%) patients had detectable serum hepatitis B envelope antigen (n = 18) or hepatitis B virus DNA (n = 11) before treatment, and seven had associated hepatocellular carcinoma. Lamivudine was continued indefinitely after transplantation, and hepatitis B immune globulin was not used. RESULTS: The actuarial patient and graft survival rates were 84% and 81%, respectively. Five patients died of causes unrelated to hepatitis B, and 26 patients were alive at a median follow-up of 16 months (range 6-47) after transplantation. One (3.8%) patient developed recurrent hepatitis B resulting from viral breakthrough at week 53 and survived after retransplantation using adefovir and hepatitis B immune globulin treatment. The remaining 25 surviving patients had no biochemical or histologic evidence of recurrent hepatitis, and serum hepatitis B virus DNA remained negative by polymerase chain reaction. In six patients, hepatitis B surface antigen (HBsAg) persisted or reappeared in serum. Among 19 patients who became negative for HBsAg from 5 to 431 days after transplantation, 13 developed anti-HBsAb that lasted a median of 6 months (range 1-21). None of the seven patients with hepatocellular carcinoma developed recurrent tumor. CONCLUSIONS: Asian patients with chronic hepatitis B may achieve a good outcome after liver transplantation using lamivudine prophylaxis.

Adolescent↗

PubMed2001

Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years.

OBJECTIVE: To investigate whether the survival results after resection of hepatocellular carcinoma (HCC) have improved within the past decade by an analysis of a prospective cohort of patients over a 10-year period. SUMMARY BACKGROUND DATA: The surgical death rate after resection of HCC has greatly improved in recent years, but the long-term prognosis remains unsatisfactory. It remains unknown whether the survival results after resection of HCC have improved within the past decade. METHODS: The clinicopathologic and follow-up data of 377 patients who underwent curative resection of HCC between January 1989 and January 1999 were prospectively collected. These patients were categorized according to two time periods: before 1994 (group 1, n = 136) and after 1994 (group 2, n = 241). The two groups were compared for clinicopathologic data and survival results. The prognostic factors for disease-free survival were further analyzed to identify the factors that might have led to improved survival outcomes. RESULTS: The overall and disease-free survival results were significantly better in group 2 compared with group 1. Patients in group 2 had significantly higher proportions of subclinical presentation, small tumors, and tumors of early pTNM stage. There were also significantly lower frequencies of histologic margin involvement, less intraoperative blood loss, and a lower transfusion rate in group 2. By multivariate analysis, early pTNM stage, subclinical HCC, and no perioperative transfusion were independent favorable prognostic factors for disease-free survival. CONCLUSIONS: Significant improvement of overall and disease-free survival results after resection of HCC has been achieved within the past decade as a result of advances in the diagnosis and surgical management of HCC. Earlier diagnosis of HCC by better imaging modalities, increased detection of subclinical HCC by screening of high-risk patients, and a reduced perioperative transfusion rate were identified as the major contributory factors for the improved outcomes.

Adult↗

PubMed2001

Protein aggregation after focal brain ischemia and reperfusion.

Two hours of transient focal brain ischemia causes acute neuronal death in the striatal core region and a somewhat more delayed type of neuronal death in neocortex. The objective of the current study was to investigate protein aggregation and neuronal death after focal brain ischemia in rats. Brain ischemia was induced by 2 hours of middle cerebral artery occlusion. Protein aggregation was analyzed by electron microscopy, laser-scanning confocal microscopy, and Western blotting. Two hours of focal brain ischemia induced protein aggregation in ischemic neocortical neurons at 1 hour of reperfusion, and protein aggregation persisted until neuronal death at 24 hours of reperfusion. Protein aggregates were found in the neuronal soma, dendrites, and axons, and they were associated with intracellular membranous structures during the postischemic phase. High-resolution confocal microscopy showed that clumped protein aggregates surrounding nuclei and along dendrites were formed after brain ischemia. On Western blots, ubiquitinated proteins (ubi-proteins) were dramatically increased in neocortical tissues in the postischemic phase. The ubi-proteins were Triton-insoluble, indicating that they might be irreversibly aggregated. The formation of ubi-protein aggregates after ischemia correlated well with the observed decrease in free ubiquitin and neuronal death. The authors concluded that proteins are severely damaged and aggregated in neurons after focal ischemia. The authors propose that protein damage or aggregation may contribute to ischemic neuronal death.

Animals↗

PubMed2001

Efficient homolactic fermentation by Kluyveromyces lactis strains defective in pyruvate utilization and transformed with the heterologous LDH gene.

A high yield of lactic acid per gram of glucose consumed and the absence of additional metabolites in the fermentation broth are two important goals of lactic acid production by microrganisms. Both purposes have been previously approached by using a Kluyveromyces lactis yeast strain lacking the single pyruvate decarboxylase gene (KlPDC1) and transformed with the heterologous lactate dehydrogenase gene (LDH). The LDH gene was placed under the control the KlPDC1 promoter, which has allowed very high levels of lactate dehydrogenase (LDH) activity, due to the absence of autoregulation by KlPdc1p. The maximal yield obtained was 0.58 g g(-1), suggesting that a large fraction of the glucose consumed was not converted into pyruvate. In a different attempt to redirect pyruvate flux toward homolactic fermentation, we used K. lactis LDH transformant strains deleted of the pyruvate dehydrogenase (PDH) E1alpha subunit gene. A great process improvement was obtained by the use of producing strains lacking both PDH and pyruvate decarboxylase activities, which showed yield levels of as high as 0.85 g g(-1) (maximum theoretical yield, 1 g g(-1)), and with high LDH activity.

Culture Media↗

PubMed2001

The management of gingival and esthetic problems: a clinical case.

The coordinated management of gingival and esthetic problems is important in dentistry. In addition, the most difficult variable to control in the treatment of anterior esthetics is the soft tissue. This article discusses the relationship between the surrounding soft tissue and the emerging crown form. The authors introduce a soft-tissue index model technique that will help the technician in fabricating the final crown with a form similar to the provisional. In this case report, provisional crowns are fabricated with enough tissue support to provide for an optimal crown-gingival interface. The present case demonstrates how to manage the gingival margin in the provisional stage and how to transfer the provisional and soft tissue to the laboratory model.

Adult↗

PubMed2001

[Clinical observation on treatment of non-small cell lung cancer with Chinese herbal medicine combined with bronchial arterial infusion chemotherapy].

OBJECTIVE: To explore the effect of treatment for non-small cell lung cancer (NSCLC) with Chinese herbal medicine (CHM) combined with bronchial arterial infusion chemotherapy (BAIC). METHODS: Patients with moderate or advanced NSCLC were randomly divided into two groups, the 39 patients in the treated group treated with CHM plus BAIC therapy and 37 in the control group treated with BAIC alone. The short-term therapeutic effect, long-term survival rate, changes of clinical principal symptoms, quality of life and peripheral blood pictures in the two groups were observed and compared. RESULTS: After treatment the rate of CR + PR + NC in the treated and the control group was 92.31% and 70.27% respectively, the inter-group comparison showed a significant difference (P < 0.05). The 0.5-, 1- and 2-year survival rate in the treated group was 79.49%, 56.41% and 51.28% respectively and in the control group, 72.97%, 51.35% and 24.32% respectively. The 2-year survival rate in the former was better than that in the latter (P < 0.05). Moreover, the improvement of clinical symptoms, Karnofsky scoring, body weight and peripheral blood picture in the treated group was superior to that in the control group. CONCLUSION: Therapeutic effect of BAIC could be enhanced by combining it with CHM.

Adenocarcinoma↗

PubMed2000

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.

BACKGROUND: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS: After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS: Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.

Adult↗

PubMed2000

Protein aggregation after transient cerebral ischemia.

Protein aggregates containing ubiquitinated proteins are commonly present in neurodegenerative disorders and have been considered to cause neuronal degeneration. Here, we report that transient cerebral ischemia caused severe protein aggregation in hippocampal CA1 neurons. By using ethanolic phosphotungstic acid electron microscopy (EM) and ubiquitin immunogold EM, we found that protein aggregates were accumulated in CA1 neurons destined to die 72 hr after 15 min of cerebral ischemia. Protein aggregates appeared as clumps of electron-dense materials that stained heavily for ubiquitin and were associated with various intracellular membranous structures. The protein aggregates appeared at 4 hr and progressively accumulated at 24 and 48 hr of reperfusion in CA1 dying neurons. However, they were rarely observed in dentate gyrus neurons that were resistant to ischemia. At 4 hr of reperfusion, protein aggregates were mainly associated with intracellular vesicles in the soma and dendrites, and the nuclear membrane. By 24 hr of reperfusion, the aggregates were also associated with mitochondria, the Golgi apparatus, and the dendritic plasmalemma. High-resolution confocal microscopy further demonstrated that protein aggregates containing ubiquitin were persistently and progressively accumulated in all CA1 dying neurons but not in neuronal populations that survive in this model. We conclude that proteins are severely aggregated in hippocampal neurons vulnerable to transient brain ischemia. We hypothesize that the accumulation of protein aggregates cause ischemic neuronal death.

Animals↗

PubMed2000

Active intracellular domain of Notch enhances transcriptional activation of CCAAT/enhancer binding protein beta on a rat pregnancy-specific glycoprotein gene.

Pregnancy-specific glycoproteins (PSGs) are primarily expressed in the placenta and become the major glycoproteins at term. To understand the regulation of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and delineated three nuclear protein binding sites: FPI, -II, and -III in the 5'-flanking region of the gene. The FPII-binding factor is shown to be C/EBPbeta, which positively regulates rnCGM3 expression [Chen, H., et al. (1995) DNA Cell Biol. 14, 681-688]. In the current study, we used the yeast one-hybrid system to isolate transcription factors binding to the FPIII site and demonstrated that a rodent J kappa recombination signal sequence binding protein, rRBPJ kappa-2N, bound to the FPIII site. Electrophoretic mobility shift assay with rat placental nuclear proteins revealed a constitutive occupancy of the FPIII site by RBPJ kappa. By transient expression analyses, we demonstrated that rRBPJ kappa-2N repressed the expression from an FPIII-driven SV40 promoter. However, this repression effect was counteracted by the active intracellular domain of Notch (NotchIC). Using the native rnCGM3 promoter construct, we demonstrated that the promoter activity stimulated by C/EBP beta was also repressed by rRBPJ kappa-2N but enhanced by NotchIC. Additionally, we found that NotchIC can stimulate expression through another RBPJkappa site within the FPI site. A functional interaction between factors binding to the FPI, FPII, and FPIII sites is proposed.

Animals↗

PubMed2000

Primary structure and function analysis of the Abrus precatorius agglutinin A chain by site-directed mutagenesis. Pro(199) Of amphiphilic alpha-helix H impairs protein synthesis inhibitory activity.

Abrus agglutinin (AAG), a low-toxicity protein from the plant Abrus precatorius, is less lethal than abrina (ABRa) in mice (LD(50) = 5 mg/kg versus 20 microg/kg of body weight). Nucleotide sequence analysis of a cDNA clone encoding full-length AAG showed an open reading frame with 1641 base pairs, corresponding to a 547-amino acid residue preproprotein containing a signal peptide and a linker region (two amino acid residues) between the AAG-A and AAG-B subunits. AAG had high homology to ABRa (77.8%). The 13 amino acid residues involved in catalytic function, which are highly conserved among abrins and ricins, were also conserved within AAG-A. The protein synthesis inhibitory activity of AAG-A (IC(50) = 3.5 nM) was weaker than that of ABRa-A (0.05 nM). Molecular modeling followed by site-directed mutagenesis showed that Pro(199) of AAG-A, located in amphiphilic helix H and corresponding to Asn(200) of ABRa-A, can induce bending of helix H. This bending would presumably affect the binding of AAG-A to its target sequence, GpApGpAp, in the tetraloop structure of the 28 S rRNA subunit and could be one of the major factors contributing to the relatively weak protein synthesis inhibitory activity and toxicity of AAG.

Abrin↗

PubMed2000

Safety of donors in live donor liver transplantation using right lobe grafts.

HYPOTHESIS: Right lobe donation was advocated for adult-to-adult live donor liver transplantation but the safety of the donor is still a major concern. We hypothesize that right lobe donation is safe if the lowest limit of volume of liver remnant that can support donor survival is known. DESIGN: Retrospective analysis of data collected prospectively. SETTING: Tertiary hepatobiliary surgery referral center. PATIENTS: Twenty-two live donors involved in adult-to-adult right lobe liver transplantation from May 1996 to June 1999. INTERVENTIONS: The right lobe grafts were obtained by transecting the liver on the left side of the middle hepatic vein. Liver transection was performed by using an ultrasonic dissector, without using the Pringle maneuver. The left lobe volume was measured by computed tomographic volumetry and the ratio of left lobe volume to the total liver volume was calculated. MAIN OUTCOME MEASURES: Hospital mortality rate and complication rate. RESULTS: The median blood loss was 719 mL (range, 200-1,600 mL). Only one donor, who had thalassemia, received 1 U of homologous blood transfusion. Postoperative complications included wound infection, incision hernia, and cholestasis in 1 donor whose liver showed 20% fatty change and who had a left lobe-total liver volume of 0.34. Another donor with 15% fatty change in the liver and a left lobe-total liver volume ratio of 0.27 developed prolonged cholestasis. Two other donors with left lobe-total liver volume ratios of 0.27 but with mild steatosis (<5%) did not develop postoperative cholestasis. Postoperative complications also included 1 case of biliary stricture and 1 case of small bowel obstruction. Both complications were adequately treated. There was no donor mortality. All donors are well and have returned to their previous occupations. CONCLUSION: Live donation of right lobe graft for adult-to-adult liver transplantation is safe provided that the residual liver volume exceeds 30% of the total liver volume and the liver itself is normal or only mildly affected by steatosis.

Adolescent↗

PubMed2000

Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence.

BACKGROUND AND OBJECTIVES: The role of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) has remained controversial, and its efficacy for postresection intrahepatic recurrence has not been fully assessed. A study was performed to evaluate the treatment results and prognostic factors of TACE treatment in these patients. METHODS: Clinicopathologic data and treatment results of 384 patients with inoperable HCC and 100 patients with postresection recurrent HCC treated with TACE were collected prospectively and analyzed. RESULTS: TACE was associated with an overall treatment morbidity rate of 23% (112/484) and mortality rate of 4.3% (21/484). A particularly high mortality rate of 20% (9/45) was observed among patients with tumors > 10 cm and pretreatment serum albumin level </= 35 g/L. The overall 1-year, 3-year, and 5-year survival rates from the time of first TACE treatment were 49%, 23%, and 17% respectively. Tumor size </= 10 cm and serum albumin level > 35 g/L were independent favorable prognostic factors. TACE in patients with postresection recurrent HCC was associated with less morbidity, mortality, and a better survival outcome compared with patients with primary inoperable HCC, but this was largely related to smaller tumor size and better liver function in the former group at the time of TACE treatment. CONCLUSIONS: TACE in patients with inoperable HCC was associated with significant morbidity and mortality, and the survival benefit was limited. Better patient selection in terms of tumor size and liver function may improve treatment results. Patients who have a tumor > 10 cm and poor liver function (serum albumin </= 35 g/L) may not be suitable candidates for TACE treatment.

Adult↗

PubMed2000

Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver.

Increasing evidence regarding free radical-generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t-BHP to induce hepatotoxicity in vitro and in vivo and determined the antioxidative bioactivity of esculetin, a coumarin compound. Our investigations showed that pretreatment with esculetin (5-20 microg/ml) significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT), and also decreased the formation of malondialdehyde (MDA) in primary cultured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo study in rats showed that pretreatment with esculetin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems.

Animals↗