Curcumin attenuated paracetamol overdose induced hepatitis.

AIM: To investigate whether curcumin could attenuate hepatitis in mice with paracetamol overdose. METHODS: Male mice were divided into four groups. Group 1 (control, n = 8); was fed with distilled water; Group 2 [N-acetyl-P-aminophenol (APAP), n = 8]; was fed with a single dose of 400 mg/kg APAP dissolved in distilled water; Group 3 [APAP + curcumin (CUR) 200, n = 8], was fed with a single dose of 400 mg/kg APAP and 200 mg/kg CUR; Group 4 (APAP + CUR 600, n = 8), was fed with a single dose of 400 mg/kg APAP and 600 mg/kg CUR. Twenty-four hours later, the liver was removed to examine hepatic glutathione (GSH), hepatic malondialdehyde (MDA), and histopathologically. Then whole blood was withdrawn from heart to determine transaminase (serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase) and inflammatory cytokines [interleukin (IL)-12 and IL-18] levels by enzyme linked immunosorbent assay. RESULTS: Serum transaminase, hepatic MDA, and inflammatory cytokines increased significantly in the APAP compared with the control group. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups significantly decreased these parameters compared with the APAP group. The level of GSH decreased significantly in the APAP compared with the control group. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups significantly increased these parameters compared with the APAP group. The histological appearance of the liver in the control group showed normal. In the APAP-treated group, the liver showed extensive hemorrhagic hepatic necrosis at all zones. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups, caused the liver histopathology to improve. In the APAP + CUR 200 group, the liver showed focal necrosis and but the normal architecture was well preserved in APAP + CUR 600 group. CONCLUSION: APAP overdose can cause liver injury. Results indicate that curcumin prevents APAP-induced hepatitis through the improvement of liver histopathology by decreased oxidative stress, reduced liver inflammation, and restoration of GSH.

Curcumin suppresses gastric NF-kappaB activation and macromolecular leakage in Helicobacter pylori-infected rats.

AIM: To investigate whether curcumin could attenuate nuclear factor (NF)-kappaB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori (H. pylori)-infected rats. METHODS: Twenty-five male Sprague-Dawley rats were equally divided into five groups: control rats (Control), control rats supplemented with 600 mg/kg curcumin, H. pylori-infected rats (Hp), H. pylori-infected rats supplemented with 200 mg/kg curcumin (Hp + curI), and H. pylori-infected rats supplemented with 600 mg/kg curcumin (Hp + curII). In H. pylori-infected groups, rats were inoculated with H. pylori suspension twice a day at an interval of 4 h for 3 d. Two weeks later, 200 or 600 mg/kg curcumin was given once daily to curcumin-supplemented groups for 7 d. On the day of the experiment, macromolecular leakage in gastric mucosa was examined by intravital fluorescence microscopy. The stomach tissue was removed to examine NF-kappaB p65 expression in gastric epithelial cells by immunohistochemistry. RESULTS: The expression of NF-kappaB p65 in gastric epithelial cells and the macromolecular leakage from gastric mucosal microcirculation significantly increased in the Hp group compared with the Control group. The percentages of NF-kappaB p65 immunoreactive cells in Control and Hp groups were 10.72% +/- 2.10% vs 16.02% +/- 2.98%, P = 0.004, respectively. The percentages of macromolecular leakage in Control and Hp groups were 10.69% +/- 1.43% vs 15.41% +/- 2.83%, P = 0.001, respectively. Curcumin supplementation in Hp + curI and Hp + curII groups significantly decreased NF-kappaB p65 immunoreactive cells and macromolecular leakage compared with results in the Hp group. The percentages of NF-kappaB p65 immunoreactive cells in Hp + curI and Hp + curII groups were 11.79% +/- 2.13% (P = 0.017) and 11.42% +/- 1.68% (P = 0.010), respectively. The percentages of macromolecular leakage in Hp + curI and Hp + curII groups were 12.32% +/- 2.13% (P = 0.025) and 12.14% +/- 1.86% (P = 0.018), respectively. CONCLUSION: H. pylori-induced gastric inflammation in rats is associated with increased NF-kappaB activation and macromolecular leakage which can be reduced by curcumin supplementation.

Ten-day sequential therapy of Helicobacter pylori infection in Thailand.

OBJECTIVES: Antimicrobial resistance has decreased eradication rates of Helicobacter pylori worldwide. The objective of this study was to determine whether a sequential therapy regimen is effective in eradicating H. pylori in adults with nonulcer dyspepsia or peptic ulcer disease in Thailand. METHODS: A total of 115 patients with dyspepsia or peptic ulcer were enrolled in the study. (14)C-urea breath test, upper endoscopy, rapid urease test, bacterial culture, and antibiotic resistance assessment were conducted during the course of the treatment. In all, 115 patients underwent a 10-day sequential regimen, which consisted of lansoprazole (30 mg) plus amoxicillin (1 g) twice a day for 5 days, then lansoprazole (30 mg) with metronidazole (500 mg) twice a day, and clarithromycin (1,000 mg) once a day for another 5 consecutive days. Successful eradication was evaluated by negative urea breath test at least 4 weeks after stopping treatment. RESULTS: Successful eradication was achieved in 106 of 115 patients (95%). All patients completed the treatment, without any dropouts. Mild adverse effects included headache and palpitations. The prevalence rate of clarithromycin-resistant H. pylori was found to be 6.1%. CONCLUSIONS: The 10-day sequential treatment for H. pylori is well tolerated and provides a high eradication rate. This regimen can overcome the emergence of antibiotic resistance and may have a role as a first-line treatment for H. pylori infection in Thailand.

Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats.

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-kappaB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-kappaB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARgamma protein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-kappaB activation.

Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats.

This research was aimed to investigate anti-inflammatory effects of Aloe vera on leukocyte-endothelium in the gastric microcirculation of Helicobacter pylori (H. pylori)-infected rats. Thirty-six male Sprague-Dawley rats were divided into 3 groups: control, H. pylori-infected, and A. vera-treated group (200 mg/kg b.w., twice daily). H. pylori-inoculation was induced in the rats by the administration of H. pylori solution. Intravital fluorescence videomicroscopy was used to examine leukocyte adhesion in postcapillary venules on the posterior surface of stomach area on different periods after administration of A. vera. Serum tumor necrosis factor-alpha (TNF-alpha) level was measured in blood collected at the end of experiment by using ELISA technique. The results showed that in H. pylori-infected group on day 8, the leukocyte adhesion was 13.40+/-1.00 cells/100 microm vessel length and the TNF-alpha was 76.76+/-23.18 pg/ml, which increased significantly (p < 0.05), compared with the control group (leukocyte adhesion(control) = 2.54+/-0.6 cells/100 microm vessel length and TNF-alpha(control) = 9.92+/-2.62 pg/ml). Treatment with A. vera reduced the leukocyte adhesion (5.5+/-0.5 cells/100 microm vessel length), and TNF-alpha (26.31+/-6.38 pg/ml) significantly (p < 0.05). In conclusion, H. pylori enhanced leukocyte-endothelium interaction in the posterior stomach area markedly. This enhancement in leukocyte-endothelium interaction could be improved by the treatment of A. vera, associated with reduction in TNF-alpha level.

Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats.

AIM: To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS: Male Spraque-Dawley rats (n=48) were divided into four groups. Group1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-alpha and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS: On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05) increased in the ulcer groups when compared to the control group. The level of TNF-alpha was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-alpha had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-alpha were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-alpha level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION: Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-alpha level and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-alpha level, elevate IL-10 level and promote gastric ulcer healing.

Caffeine clearance in patients with hepatocellular carcinoma after transcatheter oily chemoembolization treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common neoplasm worldwide, particularly in Asia, with a grave prognosis. Transcatheter Oily Chemoembolization (TOCE) is now universally accepted as the method of choice for the treatment of inoperable HCC. The purpose ofthis study was to evaluate caffeine clearance, a quantitative liver function assessment, in HCC patients before and after treatment with TOCE. METHOD: Both conventional liver function test (LFT) and caffeine clearance were evaluated in twelve patients. Each patient took a 3.5 mg/kg single oral dose of caffeine solution before TOCE, 1 day and 5 weeks after treatment. Blood samples were subsequently collected at 0.5, 1.5, 3, 5, 10 and 24 hours after each dose of caffeine administration and assayed for serum caffeine level by the HPLC technique. Clearance (Cl) was calculated using the equation of Cl = Kel x Vd (Kel = elimination rate constant, Vd = volume of distribution) and half-life was determined using pharmacokinetic analysis. RESULTS: The mean caffeine clearance 1 day after TOCE (0.51 +/- 0.096) and 5 weeks after TOCE treatment (0.43 +/- 0.07) was significantly reduced compared with the mean caffeine clearance before treatment (0.79 . 0.2 ml/min x kg) with the p = 0.06 and p = 0.03, respectively. No significant changes (p > 0.05) in most conventional LFT were observed 5 weeks after treatment. CONCLUSIONS: In the present study, the authors found that caffeine clearance was reduced after TOCE in patients with HCC inspite of no changes in conventional LFT. Thus, the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in HCC patients post TOCE treatment.