Serum Hepatic Markers Research Articles

MicroRNA-221 inhibition in hepatocytes ameliorates liver fibrosis

Excessive extracellular matrix accumulation due to chronic liver injury leads to fibrosis, cirrhosis and may then eventually, progress to hepatocellular carcinoma. Small non-coding microRNAs (miRNAs) play important roles in the regulation of multiple liver functions and diseases. Among various miRNAs, miR-221 has recently been reported to be upregulated in liver fibrosis, and its expression correlates with severity of liver fibrosis in HCV patients. We show that downregulation of miR-221 in hepatocytes can ameliorate liver fibrosis by decreasing the activation of HSCs. We inhibited miR-221 expression by an adeno-associated virus encoding a tough decoy against miR-221 (AAV TuD). Reduced levels of serum transaminases and hepatic fibrotic markers were found in mice injected with AAV TuD. Therefore, our findings indicate that suppression of miR-221 in hepatocytes ameliorates liver fibrosis. Our study provides a novel therapeutic approach for the treatment of liver fibrosis via miRNA modulation.

Honey has a protective effect against chlorpyrifos-induced toxicity on lipid peroxidation, diagnostic markers and hepatic histoarchitecture

Abstract Introduction Currently, there is increasing interest in the identification of natural sources of antioxidants that have minimal side effects and can be used as preventive medicine. In this study, the protective role of honey against oxidative damage and hepatotoxicity induced by sub-chronic exposure to chlorpyrifos (CPF) was investigated. Methods Female Wistar rats ( n = 24) were randomly divided into the following four groups: (1) control, (2) honey-treated (3.0 g/kg), (3) CPF-treated (5.4 mg/kg) and (4) honey (3.0 g/kg) + CPF (5.4 mg/kg) treatments. All of the doses were administered daily via oral gavage for 4 weeks. Results Oral exposure to CPF caused hepato- and nephrotoxicity as indicated by the marked elevation in the serum hepatic marker enzymes (the transaminases and alkaline phosphatase activities), the total bilirubin, total cholesterol, triglycerides, urea, creatinine and hepatic lipid peroxidation levels, whereas the serum total protein level was significantly lower compared with the control. A significant decrease in the body weight gain and an increase in the absolute and relative liver weights were observed in the CPF-treated animals compared with the control. The biochemical alterations observed were accompanied by histopathological changes marked by the appearance of degenerative necrosis, congestion, inflammation and edema in the liver section. However, co-treatment with honey ameliorated the changes in the investigated biochemical parameters and the changes in the body and liver weights as revealed by the inhibition of lipid peroxidation and the improvement observed histopathologically. Conclusions The present study suggests that honey has a protective potential for the alleviation of hepatic and renal toxicities induced by CPF.

Abstract 11089: Hepatic Abnormalities are Present Before and Early After the Fontan Operation

Objectives: Progressive hepatic fibrosis is common after the Fontan operation, but little is known about its onset. We sought to determine if there is non-invasive evidence of hepatic injury prior to the Fontan operation, and if further injury is seen soon after the procedure. Methods: Patients undergoing the Fontan operation at our institution were prospectively enrolled and underwent hepatic ultrasound with Doppler and serum testing immediately before and 3 to 6 months after the operation. Results: Thirty patients were enrolled at a median age at time of the Fontan operation of 3.1 yrs (range: 2.2-8.1 yrs). An extracardiac Fontan operation was performed in 67% and nearly all (97%) underwent fenestration. Three patients (10%) had abnormal hepatic echotexture prior to the Fontan operation. At the post-Fontan study, mean liver length increased (9.9 vs. 10.9 cm, p<0.0001) and mean hepatic artery end diastolic velocity decreased (18.8 vs. 14.5 cm/sec, p=0.03). One patient showed new, abnormal hepatic echotexture after surgery. Among serum indices, mean aspartate aminotransferase (56.7 vs. 60.7 IU, p=0.04), mean alanine transaminase (ALT) (18.9 vs. 33.9 IU, p=0.0002), and mean gamma-glutamyl transferase (GGT) (18.7 vs. 46.1 IU, p=0.002) increased at the post-Fontan assessment compared to the pre-operative values. By linear regression, hospital length of stay and duration with chest tube after Fontan operation were both significantly associated with an increase in GGT (p< 0.001 for both) and ALT (p=0.008, p=0.04) 3 to 6 months after surgery. There were no associations found between change in ultrasound or serum markers of liver function and pre-Fontan hemodynamic variables as measured by echocardiogram, catheterization, and/or magnetic resonance imaging. Conclusions: Hepatic ultrasound abnormalities were seen prior to the Fontan operation in some patients. Early after the Fontan operation, liver length and serum hepatic markers were increased relative to pre-Fontan values. Post-operative morbidity was associated with an increase in these serum markers. In total, these findings suggest that liver insult may occur prior to the Fontan operation and further insult likely begins soon after the Fontan circulation is created.

Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats

The present study was to evaluate the protective role of hesperidin (HDN) against iron-induced hepatic and renal toxicity in rats. Administration of iron (30mg/kg body weight) intraperitoneally for 10 days, the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers and iron concentration in blood were significantly (p<0.05) increased. The toxic effect of iron was also indicated by significant (p<0.05) decrease in the levels of plasma, liver and kidney of enzymatic and non-enzymatic antioxidants. Administration of hesperidin at different doses (20, 40 and 80mg/kg body weight) significantly (p<0.05) reversed the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers, restored the levels of hepatic, renal enzymatic antioxidants and non-enzymatic antioxidants with decrease in iron concentration in blood. Hesperidin at a dose of 80mg/kg body weight exhibits significant protection on hepatic and renal when compared with other two doses (20 and 40mg/kg body weight). All these changes were corroborating by histological observations of liver and kidney. This study demonstrated the protective role of hesperidin in reducing toxic effects of iron in experimental rats.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats.

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.

Dimethoxycurcumin potentially protects arsenic induced oxidative hepatic injury, inflammation and apoptosis via Nrf2-Keap1 signaling in rats

Abstract NADPH oxidase mediated ROS generation plays a decisive role in the pathogenesis of arsenic (As) hepatotoxicity. Antioxidant phytochemicals, like dimethoxycurcumin (DiMC) has a tremendous scope in attenuating the ROS mediated hepatic injury. Hence, the present study has been designed to investigate the hepatoprotective action of DiMC by analysing the markers of hepatic oxidative stress, pro-inflammatory cytokines, apoptotic markers and antioxidant competence in As (5 mg/kg BW) induced hepatotoxic rats. Oral administration of DiMC (80 mg/kg BW) to As intoxicated rats showed a significant amelioration in the levels of serum hepatic markers, pro-inflammatory cytokines and the expression of NADPH oxidase subunits (Nox2, Nox4, and p47phox) in liver. The elevated levels of hepatic oxidative stress markers lipid peroxides, hydroperoxides, protein carbonyls and conjugated dienes and decreased levels of enzymatic and non-enzymatic antioxidants status were also reverted back to near normalcy by DiMC when compared with As treated rats. In addition, mRNA and protein expression analysis also confirms that DiMC pre-treatment significantly downregulates the NOX subunits and upregulates the Nrf2 and its related enzymes in the liver. Studies on the mechanism of apoptosis showed that As accelerated the markers of mitochondrial dependent apoptotic pathway (enhanced cytochrome c release in cytosol from mitochondria, altered the expression of Bax, Bcl-2, Bad, caspase-9, caspase-3). However, DiMC pre-treatment effectively restored the As-induced alterations in liver. Histological and immunohistochemical results were also evidenced that DiMC potentially protects the liver from As-induced oxidative stress, inflammation and apoptosis. These findings encourage the use of DiMC as a prospective salutary entity for As hepatotoxicty through the suppression of NADPH oxidase and Nrf2 activation.

Ameliorating effect of Phoenix dactylifera on lambda cyhalothrin induced biochemical, hematological and hepatopathological alterations in male wistar rats

Abstract Lambda cyhalothrin (LTC) is a synthetic pyrethroid insecticide, widely used to control insect pests in agriculture, public health, and homes and gardens. In the present study, an attempt has been made to study the effect of lambda cyhalothrin on biochemical, hematological parameters and ameliorating effects of palm dates ( Phoenix dactylifera) in male wistar rat. Adult male Wistar rats were divided into four different groups. Group I served as control; group II received lambda cyhalothrin at a dose of 8 mg/kg (1/10 LD50) dissolved in water for 21 days orally; group III received P. dactylifera (200 mg/kg BW for 21 days) orally; group IV P. dactylifera alone treated. LTC-induced liver toxicity was measured by the increased activities of serum hepatic marker enzymes like aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, along with increased elevation of lipid peroxidation and reduction in the levels of enzymic and non-enzymic antioxidants levels. Lambda cyhalothrin exposure leads to adverse effects on hematological parameters including erythrocyte (RBCs) and leukocyte (WBCs) counts, hemoglobin concentration (Hb), hematocrit (Hct) and blood indices (MCV and MCH). However, treatment with P. dactylifera normalized the levels of hepatic markers, antioxidant and non-enzymic antioxidant, lipid peroxidation products and all the hematological parameters. These findings highlight the efficacy of P. dactylifera as protective effects against lambda cyhalothrin induced toxicity.

The use of microencapsulated hepatocytes transplantation reduces mortality and liver alterations in Schistosoma mansoni infected hamsters.

Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotropic liver transplantation. The goal of this work was to study the adequacy of intrasplenic hepatocyte transplantation (HCTx) in fresh and microencapsulated forms, in a hamster model of liver fibrosis by Schistosoma mansoni infected hamsters were divided into 6 groups; untreated for 11 weeks (GI) and for 15 weeks (GII), treated with praziquantel (PZQ) 7 weeks PI, and killed 4 weeks (GIII) and 8 weeks (GIV) post-treatment. Treated with PZQ 7 weeks PI, and then treated orally with immunosuppressive drug "cyclosporine (4 weeks post PZQ treatment), 24 hr. before interasplenic injection with fresh hepatocytes (V). Treated with PZQ 7 weeks PI, and then injected interasplenically (4 weeks post-treatment) with microencapsulated hepatocytes (GVI). GI & GIII were killed 11 weeks PI for assessment the anti-schistosomal efficacy of PZQ. The other four groups were killed 15 weeks PI for investigation of liver and spleen histology, serum liver enzymes and hepatic oxidative markers before and after HCTx. Freshly isolated hepatocytes with a mean viability 92.97 +/- 1.2% were used for microencapsulation and transplantation. Histological study showed the presence of transplanted hepatocytes in spleen of recipient. PZQ accelerated healing of hepatic granulomatous lesions as evidenced parasitologically by the increase in the percentage of dead eggs and histologically showing more granuloma circumscription with more ova degeneration and less inflammatory cells. The 25-day survival rates in GII, GIV, GV& GVI were 5/15 (33.3%), 8/15 (53.3%), 10/15 (66.7%) and 9/15 (60%) respectively. In addition, there were significantly better outcomes in serum biochemical indexes such as ALT, AST, gamma-GT, ALP, and hepatic SOD and MDA in the fresh and microencapsulated groups than in PZQ-treated group, without great differences between the microencapsulated and the fresh transplanted groups. Liver pathological staining supported these findings.

Valproic acid prevents the deregulation of lipid metabolism and renal renin–angiotensin system in l-NAME induced nitric oxide deficient hypertensive rats

The present study was aimed to investigate the antihyperlipidemic and renoprotective potential of valproic acid against N(ω)-nitro-L arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), kidney weight, levels of oxidative stress markers in tissues were increased. Dyslipidemia was also observed in hypertensive rats. Moreover, enzymatic and nonenzymatic antioxidant network also deregulated in tissues. Valproic acid (VPA) supplementation daily for four weeks brought back all the above parameters to near normal level and showed no toxicity which was established using serum hepatic marker enzyme activities and renal function markers. Moreover the up regulated expression of renin-angiotensin system (RAS) components were also attenuated by VPA treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that VPA has enough potential to attenuate hypertension, dyslipidemia and renal damage in nitric oxide deficiency induced hypertension.

Antihypercholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle, and Its Active Constituent, Eugenol, in Triton WR-1339-Induced Hypercholesterolemia in Experimental Rats.

Hypercholesterolemia is a dominant risk factor for atherosclerosis and cardiovascular diseases. In the present study, the putative antihypercholesterolemic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were evaluated in experimental hypercholesterolemia induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg b.wt) in Wistar rats. Saline-treated hypercholesterolemic rats revealed significantly higher mean blood/serum levels of glucose, total cholesterol, triglycerides, low density and very low density lipoprotein cholesterol, and of serum hepatic marker enzymes; in addition, significantly lower mean serum levels of high density lipoprotein cholesterol and significantly lower mean activities of enzymatic antioxidants and nonenzymatic antioxidants were noted in hepatic tissue samples from saline-treated hypercholesterolemic rats, compared to controls. However, in hypercholesterolemic rats receiving the Piper betle extract (500 mg/kg b.wt) or eugenol (5 mg/kg b.wt) for seven days orally, all these parameters were significantly better than those in saline-treated hypercholesterolemic rats. The hypercholesterolemia-ameliorating effect was better defined in eugenol-treated than in Piper betle extract-treated rats, being as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt). These results suggest that eugenol, an active constituent of the Piper betle extract, possesses antihypercholesterolemic and other activities in experimental hypercholesterolemic Wistar rats.

Protective role of grape seed proanthocyanidins against cadmium induced hepatic dysfunction in rats

Grape seed proanthocyanidins (GSP) are polyphenolic compounds which exert a novel spectrum of biological, pharmacological and therapeutic properties against oxidative stress. Recent findings have shown that GSP exhibit numerous antioxidant and free radical scavenging properties. So, it was of special concern to investigate the protective efficacy of GSP against cadmium induced hepatic dysfunction in rats. Male Wistar rats were treated with cadmium (Cd) as cadmium chloride (CdCl2, 5 mg kg−1 bw, orally) and orally pre-administered with GSP (100 mg kg−1 bw) 90 minutes before Cd intoxication for 4 weeks to evaluate hepatic damage of Cd and antioxidant potential of GSP. Our results demonstrate a significant (p < 0.05) increase in the levels of serum hepatic markers and hepatic oxidative stress markers and a notable (p < 0.05) decrease in hepatic enzymatic and non-enzymatic antioxidant contents along with histopathological alterations on Cd exposure. The GSP pre-treatment regimen was beneficial in the recovery of altered serum and hepatic biochemical and histological variables by Cd. Our results clearly indicate that the free radical scavenging and antioxidant potential of GSP benefits the recovery of rats exposed to Cd. We thus recommend that diets rich in GSP help in attenuating Cd-induced oxidative hepatic dysfunction in rats.

Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by improving its bioavailability and pharmacokinetics

Mangiferin is a xanthonoid present in Mangifera indica. It has been reported for a variety of pharmacological activities, including hepatoprotection. However, the major disadvantage of mangiferin is its reduced biological activity due to poor absorption, low bioavailability and rapid elimination from the body after administration. The aim of this study was to prepare a phospholipid complex of mangiferin to overcome these limitations and to investigate the impact of the complex on hepatoprotective activity and bioavailability. The results showed that the complex has an enhanced hepatoprotective and in vivo antioxidant activity as compared to pure mangiferin at the same dose level (30 and 60 mg kg⁻¹). The complex restored the levels of serum hepatic marker enzymes and liver antioxidant enzymes with respect to carbon tetrachloride-treated animals. The complex also increased the bioavailability of mangiferin in rat serum by 9.75-fold compared to pure mangiferin at the same dose level and enhanced the elimination half-life (t(1/2 el)) from 1.71 ± 0.12 h⁻¹ to 3.52 ± 0.27 h⁻¹. The results suggested that the complexation of mangiferin with soya phospholipid enhanced the hepatoprotection and in vivo antioxidant activity, which may be due to the improved bioavailability and pharmacokinetics of mangiferin in rat serum.

Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan: A community‐based cohort study

Subjects positive for antibody to hepatitis B core antigen (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are considered to have occult hepatitis B virus (HBV) infection. The aim of this study was to determine the impact of occult HBV infection on aggravation of the clinical course in hepatitis C virus (HCV) carriers. A prospective cohort study was performed in 400 subjects who were positive for anti-HCV antibody and negative for HBsAg. Among these subjects, 263 were HCV core antigen positive or HCV RNA positive (HCV carriers). We examined whether the presence of HBcAb affected the clinical course in these HCV carriers from 1996-2005. The HBcAb positive rates were 53.6% and 52.6% in HCV carriers and HCV RNA negative subjects, respectively. There were no differences in the incidence of hepatocellular carcinoma (HCC) and cumulative mortality associated with liver-related death between HCV carriers who were positive and negative for HBcAb. In multivariate analysis, age (≥65 years) and alanine aminotransferase level (≥31 IU/L) emerged as independent risk factors for HCC development and liver-related death, but the HBcAb status was not a risk factor. In addition, increased serum hepatic fibrosis markers (measured from 2001-2004) were not associated with HBcAb status. In our cohort study, the presence of HBcAb had no impact on HCC development, liver-related death and hepatic fibrosis markers in HCV carriers. Thus, our results indicate that occult HBV infection has no impact on the clinical course in HCV carriers.

Chronic sulforaphane oral treatment accentuates blood glucose impairment and may affect GLUT3 expression in the cerebral cortex and hypothalamus of rats fed with a highly palatable diet

Obesity and insulin resistance are the key factors underlying the etiology of major health problems such as hypertension, diabetes and stroke. These important health issues lead researchers to investigate new approaches to prevent and treat obesity and insulin resistance. Good candidates are the phytochemical compounds that have been extensively studied in the field. Therefore, the aim of this study was to test whether sulforaphane (SFN, 1 mg kg⁻¹, 4 months treatment), a potent inducer of antioxidant enzymes present in cruciferous vegetables, had some beneficial effects on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats. Glucose tolerance, serum and hepatic lipid levels, lipid profile, ALT, AST, urea and creatinine, GLUT1 and GLUT3 levels in the cerebral cortex, hippocampus and hypothalamus were analyzed. Glucose tolerance was lower in the HP diet groups, especially in the HP group treated with SFN. Except for the liver triacylglycerols, no differences were found in serum lipids, hepatic and kidney markers of the HP diet groups. Although expression of GLUT1 was similar between groups for all three brain structures analyzed, expression of GLUT3 in the cortex and hypothalamus had a tendency to decrease in the HP diet group treated with SFN. In conclusion, SFN at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression in the cerebral cortex and hypothalamus.

Protective Effect of Black Tea Infusion on Aflatoxin-Induced Hepatotoxicity in Mice

Aflatoxins are a group of mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus and are potent inducers of hepatotoxicity. The present study was carried out to investigate the effect of black tea infusion on aflatoxin-induced hepatotoxicity in male mice. A 2% black tea infusion in drinking water was prepared and orally administered along with aflatoxin (750 and 1500μg/kg body weight) for 30 days. Morphological investigation, body weight and organ weight calculations and histopathological analysis were carried out. Serum hepatic marker enzymes namely alanine aminotransferase and aspartate aminotransferase were estimated. The results clearly indicated that aflatoxin treatment for 30 days caused significant dose-dependent reduction in body weight and increase in liver weight. The activities of ALT and AST were found to be elevated while protein content was found to be decreased in aflatoxin-treated mice as compared to vehicle control. Histopathological analysis showed hepatocellular necrosis and cytoplasmic vacuolization along with fatty infiltration in toxin-treated animals. Results revealed significant (p<0.05) restoration of aflatoxin-induced damages in body weight, organ weight, serum chemistry and histopathological features in aflatoxin plus black tea infusion administered mice in a dose dependant manner. It is concluded from the present study that supplementation of black tea infusion can be beneficial in positively modulating aflatoxin-induced alterations in liver.

Beneficial effect of Trichopus zeylanicus extract on mercuric chloride-induced hepatotoxicity in rats

The present study aimed to determine the effect of Trichopus zeylanicus leaf extract (TZ Et) on mercuric chloride (HgCl2)-induced liver toxicity in rats. Wistar albino male rats were divided into four groups. Group I was administered physiological saline as a vehicle control. Group II was administered HgCl2 (0.4 mg/kg body weight/day) intraperitoneally for 20 days. Groups III and IV were administered TZ Et orally (100 mg/kg body weight/day) for 20 days with or without intraperitoneal administration of HgCl2. Serum hepatic marker enzymes, enzymic and non-enzymic antioxidants, liver functional markers, lipid peroxidation, and liver histology were evaluated. The toxic effect of HgCl2 was indicated by the significantly (p<0.05) increased serum marker enzymes, liver functional markers, and lipid peroxidation. The activities of enzymic and non-enzymic antioxidants were significantly (p<0.05) decreased. TZ Et significantly (p<0.05) prevented these pathological alterations as observed by histology. The present study concludes that TZ Et has the ability to alleviate the hepatotoxic effects caused by HgCl2 in rats.

Meta-analysis: silymarin and its combination therapy for the treatment of chronic hepatitis B

Silymarin is used by many patients with chronic hepatitis B, but its efficacy remains unknown. The aim of this investigation was to conduct a meta-analysis to determine the efficacy and safety of silymarin and its combination therapy for the treatment of chronic hepatitis B. We searched Chinese and English reports from January 1966 to December 2011, using 12 databases. Two reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated silymarin and its combination therapy for the treatment of chronic hepatitis B. Twelve trials satisfied the eligibility criteria for this meta-analysis. Silymarin was equivalent to antiviral drug or protection liver drugs in serum transaminases, viral load and hepatic fibrosis markers. But silymarin combined with antiviral drug or antiviral drug and protection liver drugs significantly reduced the level of serum transaminases, hepatic fibrosis markers and serum TGF-β1, TNF-α, IL-6 versus antiviral drug or protection liver drugs. Silymarin combined with protection liver drugs significantly reduced the level of serum transaminases, TBIL, hepatic fibrosis markers and was equivalent to protection liver drugs in the normalisation rates of serum transaminases, TBIL, but protection liver drugs significantly increased the improvement rates of hepatic fibrosis markers. Silymarin combined with antiviral drug or antiviral drug and protection liver drugs may have potential therapeutic value. Treatment with silymarin appears to be safe and well tolerated. The data are too limited to exclude a substantial benefit or harm of silymarin and its combination therapy on serum transaminases, and also to support recommending this herbal compound for the treatment of chronic hepatitis B.

S120 Update on the UK CF Gene Therapy Consortium Multidose, Non-Viral, Gene Therapy Trial

The UK CF GTC has been working for several years to determine the clinical benefit of CFTR gene therapy. Our premise was that for such a therapy to achieve clinical...

Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats

Hypercholesterolemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. In the present study, an attempt was made to evaluate the putative antihypercholesterolemic and antioxidative effects of an ethanolic extract of the oyster mushroom (Pleurotus ostreatus) and chrysin, one of its major components, in hypercholesterolemic rats. Hypercholesterolemia was induced in rats by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight (b.wt.)), which resulted in persistently elevated blood/serum levels of glucose, lipid profile parameters (total cholesterol, triglycerides, low-density lipoprotein-, and very low-density lipoprotein-cholesterol), and of hepatic marker enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase). In addition, lowered mean activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and lowered mean levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) were observed. Oral administration of the mushroom extract (500 mg/kg b.wt.) and chrysin (200 mg/kg b.wt.) to hypercholesterolemic rats for 7 days resulted in a significant decrease in mean blood/serum levels of glucose, lipid profile parameters, and hepatic marker enzymes and a concomitant increase in enzymatic and nonenzymatic antioxidant parameters. The hypercholesterolemia-ameliorating effect was more pronounced in chrysin-treated rats than in extract-treated rats, being almost as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt.). These results suggest that chrysin, a major component of the oyster mushroom extract, may protect against the hypercholesterolemia and elevated serum hepatic marker enzyme levels induced in rats injected with Triton WR-1339.

Ursodeoxycholic acid stimulates the formation of the bile canalicular network

Ursodeoxycholic acid (UDCA) is a hepatoprotective bile acid used in the treatment of chronic liver diseases. Although several pharmacological effects, including choleresis and inhibition of apoptosis, have been proposed, the impact of UDCA on hepatic structure is not well understood. Here, the influence of UDCA on bile canalicular (BC) morphology was evaluated in vitro in immortalized rat hepatocytes (McA-RH 7777 cells) and primary rat hepatocytes. Cells cultured for 3 days in the presence of UDCA, the BC lumen was enlarged and the bile canaliculi were surrounded by multiple cells (≥5) with a continuous canal-like structure, reminiscent of the in vivo BC network. The effects were dependent on p38MAPK and conventional PKC in McA-RH cells, and partially dependent on p38MAPK, MAPK/ERK kinase, and conventional PKC in primary rat hepatocytes. These findings were then studied in vivo in a rat model of dimethylnitrosamine-induced hepatic injury, in which the BC network is significantly disrupted. In accordance with the in vitro observations, administration of UDCA (40 mg/kg/day) to the injured rats for 18 days improved the BC network compared with the vehicle control. Serum hepatic markers were not altered by UDCA treatment, suggesting that the morphological effects were due to the direct actions of UDCA on network formation. Our data provide new evidence of the pharmacological potential of UDCA in accelerating or regenerating BC network formation in vitro, in hepatic cell culture models, and in vivo in a rat model of hepatic injury, and provide a basis for understanding its hepatoprotective effects.