Protective effects of Lactuca sativa ethanolic extract on carbon tetrachloride induced oxidative damage in rats

Objective

To study the protective effects of the ethanolic extract of lettuce (Lactuca sativa L. var. longifolia) leaves against the toxicity caused by carbon tetrachloride (CCl₄) in reproductive system of rats.

Methods

Lettuce leaves were dried and extracted with ethanol (plant: solvent, 1:10, w/v). The extract was filtered and evaporated to yield dried lettuce extract. Animals were divided into seven groups and treated with CCl₄ and different concentrations of lettuce extract. At the end of the experimental period, the animals were sacrificed and blood was collected and centrifuged for serum separation. Body weights, testis size, histopathology of testis and liver, catalase (CAT) activity, superoxide dismutase (SOD) activity, peroxidase (POD) activity, reduced glutathione (GSH), glutathione peroxidase activity (GSH-Px), thiobarbituric acid reactive substances (TBARS), nitrite level, and serum hormones were determined.

Results

Oxidative stress induced by CCl₄ (2 mL/kg body weight) in rat decreases the increase in body weight and relative testis weight. It also markedly increases the level of TBARS and nitrites along with corresponding decrease in reduced glutathione and various antioxidant enzymes in testis (i.e., CAT, POD, SOD and GSH-Px). Serum level of testosterone, luteinizing hormone and follicle stimulating hormone was decreased while estradiol and prolactin were increased during CCl₄ treatment. Histopathology of CCl₄-treated rats indicated the partial degeneration of germ and leydig cells along with deformities in spermatogenesis. Supplementation of lettuce extract (100, 150, 200 mg/kg body weight orally) once a week for 10 weeks results in decrease of TBARS and nitrite, while increase in antioxidant enzymes; CAT, POD, SOD, GSH-Px and GSH contents. Serum level of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, histology, body weight and relative testis weight was also concomitantly restored to near normal level by lettuce extract supplementation to CCl₄-intoxicated rat.

Conclusions

The results clearly demonstrate that lettuce extract treatment augments the antioxidants defense mechanism against CCl₄-induced toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.     

Assessment of In vivo antioxidant properties of Dacryodes edulis and Ficus exasperata as anti-malaria plants

Objective

To evaluate the phytochemical profile and potential anti-oxidant properties of Dacryodes edulis and Ficus exasperata.

Methods

Six groups of Albino rats were intoxicated with tetrachloromethane (CCl₄) for 2 d, prior to 7 d administration of 50 mg/kg, 100 mg/kg, 200 mg/kg ethanol extracts of plants and three control remidies which is Tween 80 (placebo), CCl₄ (negative control) and vitamin E (positive control). Tissue homogenates were employed in assessing the thiobarbituric acid reactive substances expressed as malondialdehyde (MDA) levels, reduced glutathione (GSH) and catalase (CAT) activities.

Results

Phytochemical profiling of the plants showed the presence of reducing sugars, flavonoids, saponins and tannins, except alkaloids and terpenoids in F. exasperata and cardiac glycosides in D. edulis. Generally, significantly different values (P<0.05) were recorded for blood than for liver homogenates. Elevated MDA levels were observed for the CCl₄ treated group (negative control). However, lower MDA levels comparable to vitamin E (positive control) were recorded for all D. edulis and the 200 mg/kg F. exasperata pre-treatments. CAT levels were significantly (P<0.05) raised in the 100 mg/kg and 200 mg/kg pretreatments for blood and the 200 mg/kg pretreatments for liver, than for Vit E. CCl₄ reduced GSH levels were reversed significantly (P<0.05) in blood by D. edulis and by the 100 mg/kg and 200 mg/kg F. exasperata pretreatments in blood and liver tissues. The mean dose-dependent analysis shows increasing fall in MDA levels with dosage.

Conclusions

The plant extracts exhibited dose-dependent oxidative stress suppressive action. This may justify their use for the traditional preparation of anti-malarial remedies.     

Bone Marrow Cells Ameliorate Liver Fibrosis and Express Albumin after Transplantation in CCl4 -Induced Fibrotic Liver

Background/Aim:

We investigated the effect of bone marrow-derived stem cell (BMSC) transplantation on carbon tetrachloride (CCl₄)-induced liver fibrosis.

Patients and Methods:

BMSCs of green fluorescent protein (GFP) mice were transplanted into 4-week CCl₄ -treated C57BL/6 mice directly to the liver, and the mice were treated for 4 more weeks with CCl₄ (total, 8 weeks). After sacrificing the animals, quantitative data of percentage fibrosis area and the number of cells expressing albumin was obtained. One-way analysis of variance was applied to calculate the significance of the data.

Results:

GFP expressing cells clearly indicated migrated BMSCs with strong expression of albumin after 28 days post-transplantation shown by anti-albumin antibody. Double fluorescent immunohistochemistry showed reduced expression of αSMA on GFP-positive cells. Four weeks after BMSC transplantation, mice had significantly reduced liver fibrosis as compared with that of mice treated with CCl₄ assessed by Sirius red staining.

Conclusion:

Mice with BMSC transplantation with continuous CCl₄ injection had reduced liver fibrosis and a significantly improved expression of albumin compared with mice treated with CCl₄ alone. These findings strengthen the concept of cellular therapy in liver fibrosis.     

Antioxidant and anti-inflammatory activity of Polygonatum sibiricum rhizome extracts

Objective

To investigate the antioxidant and anti-inflammatory activities of distilled water extract of fresh Polygonatum sibiricum (P. sibiricum) rhizome.

Methods

: The extracts were tested for antioxidant activity by using DPPH (1,1-diphenyl-2-picryl-hydrazyl), and hydroxyl (OH•) radicals scavenging activity. The level of intracellular reactive oxygen species (ROS) was determined in H₂O₂ treated chang liver cells. Anti-inflammatory activity was evaluated by the inhibition of nitric oxide (NO), inducible nitric oxide synthase (iNOS), as well as tumor necrosis factor-alpha (TNF-α) protein expression in a lipopolysaccharide stimulated Raw 264.7 murine macrophages cell line.

Results

: P. sibiricum water extracts scavenged DPPH, OH• radicals and decreased the level ROS. The extracts reduced NO reduction and inhibited the expression of iNOS and TNF-α proteins.

Conclusions

: The findings indicate that water extracts of P. sibiricum could be considered as natural antioxidants and anti-inflammatory agents for food and drug industries.     

Protective effect of Terminalia chebula against lysosomal enzyme alterations in isoproterenol-induced cardiac damage in rats

BACKGROUND:

Terminalia chebula is an ayurvedic drug recommended for the treatment of heart diseases. Earlier studies by the authors validated the beneficial cardioprotective effect of T chebula against isoproterenol-induced myocardial infarction.

OBJECTIVES:

To evaluate the therapeutic efficacy of T chebula in protecting against isoproterenol-induced lysosomal membrane damage.

METHODS:

Lysosomal enzyme activities from the serum, heart and lysosomal fractions were determined. The triphenyltetrazolium chloride assay was used to confirm the protective effect of T chebula on the myocardium.

RESULTS:

Isoproterenol administration produced significant cardiac damage (as seen by the triphenyltetrazolium chloride assay) and significantly altered lysosomal enzyme activities. Pretreatment with an ethanol extract of T chebula was found to retain near normal activities of lysosomal enzymes in rats given T chebula or T chebula plus isoproterenol compared with rats given isoproterenol alone.

CONCLUSIONS:

Pretreatment with T chebula extract stabilizes the lysosomal membrane and, thus, may have prevented myocardial damage.     

Evaluation of hepatoprotective effect of methanolic extract of Clitoria ternatea (Linn.) flower against acetaminophen-induced liver damage

Objective

To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea) flower extract against acetaminophen-induced liver toxicity.

Methods

The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis.

Results

The amount of total phenolics and flavonoids were estimated to be 105.40±2.47 mg/g gallic acid equivalent and 72.21±0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC₅₀ value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg) showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05). Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05). Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding.

Conclusion

The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.     

Low Serum Hepatitis B Surface Antigen Level Predicts Compensated Cirrhosis Caused by Chronic Hepatitis B in HBeAg Positive Patients in East China

Backgrounds:

Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection.

Objectives:

The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients.

Patients and Methods:

Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis.

Results:

Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log₁₀ IU/mL VS 4.17 Log₁₀ IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log₁₀ IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2.

Conclusions:

In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.     

Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 (LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China.

Objectives:

The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population.

Patients and Methods:

LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods.

Results:

No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL).

Conclusions:

Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.     

Serum biochemical changes in rabbits on a regular diet with and without flax lignan complex following a high-cholesterol diet

BACKGROUND:

Flax lignan complex (FLC) isolated from flaxseed suppresses development of hypercholesterolemic atherosclerosis. It does not produce regression of atherosclerosis, but prevents its regular diet-induced acceleration following a high-cholesterol diet. It is not known if replacement of a high-cholesterol diet with a regular diet has deleterious effects on body organs.

OBJECTIVES:

To determine if short-term use of a high-cholesterol diet, and a regular diet with or without FLC following the high-cholesterol diet, have any adverse effects on serum electrolytes, glucose and enzymes related to the liver, kidneys, skeletal muscle and intestines.

METHODS:

Blood samples were collected from the rabbits before and at various intervals during the high-cholesterol diet, and while on the regular diet with or without FLC, following the high-cholesterol diet. Measurements of serum total cholesterol, glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), albumin, creatinine, electrolytes (sodium [Na], potassium [K], chloride [Cl]) and carbon dioxide (CO₂) were taken.

RESULTS:

The high-cholesterol diet produced hypercholesterolemia, which was associated with reductions in serum glucose and no significant changes in serum Na, K, Cl, CO₂, ALT, ALP, AST, GGT, albumin or creatinine. Regular diet with or without FLC, following the high-cholesterol diet, reduced serum total cholesterol and glucose, increased serum Na, Cl and creatinine, but produced no significant alterations in serum K, CO₂, ALT, AST, GGT or albumin. FLC reduced serum ALP, but regular diet produced no significant change.

CONCLUSION:

Short-term use of a high-cholesterol diet, or a regular diet with or without FLC following the high-cholesterol diet, does not produce deleterious effects in the liver, kidneys, skeletal muscle, intestine or bone, as shown by changes in serum electrolytes, glucose and enzymes.     

Effects of Pentoxifylline on Non-Alcoholic Steatohepatitis: A Randomized,Double-Blind,Placebo-Controlled Trial in Iran

Background:

Non-alcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease. Several studies suggest that pentoxifylline (PTX) can improve the disease outcome.

Objectives:

We aimed to compare the effect of pentoxifylline with placebo on liver aminotransferases and cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) in patients with NASH.

Patients and Methods:

Thirty patients with NASH were included in the study, based on ultrasonography and 1.5-fold mean change from baseline serum levels of liver aminotransferases. Patients with NASH were randomized to receive 1200 mg PTX (the intervention group) or placebo (the placebo group) for 6 months. The serum levels of liver aminotransferases and cytokines were compared between the intervention and placebo groups, at various time points.

Results:

The serum levels of liver aminotransferases were significantly reduced at 3 months and at 6 months, compared with baseline, in both groups. The serum levels of IL-6 were significantly decreased, in both groups, only at 6 months, compared with baseline. Compared to the placebo group, the serum level of TNF-α was significantly decreased in the intervention group, at 6 months. The serum level of IL-8 was increased, in both groups, after 6 months, without reaching clinical significance. There was no significant difference in serum levels of liver aminotransferases and cytokines, between intervention and placebo groups.

Conclusions:

Decreases in the serum levels of liver aminotransferases and cytokines, in both groups, are related to low-calorie diets and exercise, rather than PTX.     

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury

Background:

Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells.

Methods:

The effect of bucillamine was studied in a rat model of liver ischaemia–reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM).

Results:

The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 ± 16.86 vs. 181.11 ± 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001).

Conclusion:

Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.     

Protective Effect of Salep on Liver

Background:

Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary.

Objectives:

The aim of this study was to assess salep effect on liver.

Materials and Methods:

In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups.

Results:

Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep.

Conclusions:

Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases.     

Antidiabetic activity of aqueous leaf extract of Atriplex halimus L. (Chenopodiaceae) in streptozotocin-induced diabetic rats

Objective

To investigate the antidiabetic effect of A. halimus leaf in streptozotocin-induced diabetic rats.

Methods

The aqueous extract of the plant leaf was tested for its efficacy in streptozotocin-induced diabetic rats. The extract was evaluated for its acute and short term general toxicity in male mice and for its antihyperglycemic activity using glucose tolerance test in rats. The aqueous extract was subjected to phytochemical screening and determination of total phenolic contents.

Results

The statistical data indicated the significant increase in the body weight and decrease in the blood glucose and hepatic levels. The total protein level was significantly increased when treated with the extract.

Conclusions

These results suggest that the aqueous leaf extract of A. halimus has beneficial effects in reducing the elevated blood glucose level and hepatic levels in streptozotocin-induced diabetic rats.     

Hypocholesterolemia in Patients with an Amebic Liver Abscess

Background/Aims

Many parasites induce changes in the lipid profiles of the host. Cholesterol increases the virulence of Entamoeba histolytica in animal models and in vitro culture. This study aimed to determine, in patients with an amebic liver abscess, the correlation between cholesterol and other features, such as the size and number of abscesses, standard hematological and serum chemistry profiles, liver tests, and duration of hospital stay.

Methods

A total of 108 patients with an amebic liver abscess and 140 clinically healthy volunteers were investigated. Cholesterol and triglycerides were measured in the sera. The data from medical observations and laboratory tests were obtained from the clinical records.

Results

A total of 93% of patients with an amebic liver abscess showed hypocholesterolemia not related to any of the studied parameters. Liver function tests correlated with the size of the abscess. The most severe cases of amebic liver disease or death were found in patients whose cholesterol levels continued to decrease despite receiving antiamebic treatment and hospital care.

Conclusions

Our results show that the hypocholesterolemia observed in patients with an amebic liver abscess is not related to any of the clinical and laboratory features analyzed. This is the first study relating hypocholesterolemia to severity of hepatic amebiasis.     

Serum Levels of Annexin A2 as a Candidate Biomarker for Hepatic Fibrosis in Patients With Chronic Hepatitis B

Background:

Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes.

Objectives:

To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis.

Patients and Methods:

This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA.

Results:

In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001).

Conclusions:

AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB.     

Hypoglycemic activity of Hemidesmus indicus R. Br. on streptozotocin-induced diabetic rats

OBJECTIVE:

To evaluate the antidiabetic activity of an aqueous extract of the roots of Hemidesmus indicus on blood glucose, serum electrolytes, serum marker enzymes, liver microsomal P-450 enzymes, and lipid peroxidation in the liver and kidney of streptozotocin-induced diabetic rats.

MATERIALS AND METHODS:

Effect of H. indicus extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rat models. The effect of the extract on serum electrolytes, serum levels of key glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems and lipid peroxidation in the liver and kidney of diabetic rats. One way analysis of variance and Duncan''s multiple range test was used for statistical analysis.

RESULTS:

Oral administration of H. indicus aqueous extract to fed, fasted and glucose-loaded diabetic rats decreased blood glucose level significantly at 5 h and restored serum electrolytes, glycolytic enzymes and hepatic cytochrome P-450-dependent enzyme systems by preventing the formation of liver and kidney lipid peroxides at the end of 12 weeks of the study period.

CONCLUSION:

From the studies, it can be concluded that the aqueous extract of the roots of H. indicus at a dosage of 500 mg/kg/day exhibits significant antidiabetic activity. It restores the concentrations of electrolytes, glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems to near normal level and also corrects the related metabolic alterations in experimentally induced diabetic rats. H. indicus administration also decreased liver and kidney lipid peroxidation products. On the basis of our findings, H. indicus could be used as an antidiabetic and antioxidant agent for the prevention and treatment of diabetes mellitus.     

Dietary iron intake and serum ferritin concentration in 213 patients homozygous for the HFEC282Y hemochromatosis mutation

BACKGROUND:

HFE^C282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals.

OBJECTIVE:

To determine whether dietary iron content influences iron stores in HFE^C282Y homozygotes as assessed by serum ferritin concentration.

DESIGN:

Serum ferritin concentration was measured and a dietary iron questionnaire was completed as part of the evaluation of 213 HFE^C282Y homozygotes who were identified through screening of >100,000 primary care patients at five HEmochromatosis and IRon Overload Screening (HEIRS) Study Field Centers in the United States and Canada.

RESULTS:

No significant relationships between serum ferritin concentration and dietary heme iron content, dietary nonheme iron content or reports of supplemental iron use were found.

CONCLUSION:

These results do not support recommending dietary heme or nonheme iron restrictions for HFEC^282Y homozygotes diagnosed through screening in North America.