Altered copper homeostasis and oxidative stress have been observed in patients with hepatocellular carcinoma. Non-ceruloplasmin copper, the free form, is a potent pro-oxidant than the protein bound copper. The aim of the present study was to evaluate which form of copper can be correlated with the oxidative stress in the circulation and in the malignant liver tissues of hepatocellular carcinoma patients. Hepatocellular carcinoma patients (grades II and III, n = 18) were enrolled in this study. Serum levels of total, free and bound copper, ceruloplasmin, iron, iron-binding capacity, lipid peroxidation products, and enzymatic and non-enzymatic antioxidants were quantified in serum and in malignant liver tissues and compared with those of normal samples (n = 20). A significant positive correlation between the serum non-ceruloplasmin copper and lipid peroxidation products and negative correlation with antioxidants were observed in hepatocellular carcinoma patients. In liver tissue, glutathione peroxidase, superoxide dismutase, and catalase activity were significantly decreased with concomitant elevation in oxidative stress markers. Our experiment revealed that the elevation in non-ceruloplasmin copper has high relevance with the oxidative stress than the bound copper.
Chronic pancreatitis is a serious condition associated with severe abdominal pain, and a significant percentage of patients progresses to irreversible calcification in pancreas. The present study evaluates the degree to which the levels of trace elements, copper, iron, selenium, zinc and haemoglobin-Fe(3+), in blood, serum and pancreas have any role to play in the calcification process associated with fibrosis in pancreas. Twenty-seven calcific (CCP) and 23 non-calcific chronic pancreatitis (CP) patients and equal number of age- and sex-matched normal volunteers (50) were enrolled in the study. Surgically removed pancreatic tissue and blood samples were analysed for copper, iron, selenium, zinc, protein, collagen and lipid peroxidation products in terms of malondialdehyde, protein carbonyls, glutathione, methemoglobin, methemoglobin reductase and ceruloplasmin activity levels. We could find that the pancreatic tissue levels of copper, iron, protein and collagen contents were significantly elevated in CCP patients when compared to CP patients. Serum levels of copper, free ionic copper and iron were also elevated in CCP patients. The serum and the pancreatic tissue level of zinc and selenium showed a significant decrease in CCP patients. The level of methemoglobin was elevated more significantly with the concomitant decline in the activity of methemoglobin reductase. There was a positive correlation between the pancreatic level of copper and iron with the collagen and protein levels. The results of the present study revealed that the levels of copper and iron, the pro-oxidants and zinc and selenium may influence calcification process in CCP patients. Hypoxia-related tissue injury due to the formation of oxidised haemoglobin may also contribute to the pathogenesis of calcification in pancreas.
The major objective of the study was to evaluate the gastroprotective property of andrographolide, a chief component of the leaves of Andrographis paniculata in terms of the ulcer preventive effect in rats. An acute toxicity test was conducted with different concentrations of andrographolide to determine the LD50 value. The dose responsive study was conducted in rats pretreated with andrographolide (1, 3 and 5 mg/kg) for a period of 30 days, prior to ulcer induction by administering ethanol, aspirin or by pyloric ligation. The ulcer protective efficacy was tested by determining the ulcer score, pH, pepsin, titrable acidity, gastric mucin, lipid peroxides, reduced glutathione, and enzymatic antioxidants superoxide dismutase, catalase and glutathione peroxidase in gastric tissue. The activities of H+-K+ ATPase and myeloperoxidase were also determined in gastric tissue. The LD50 value was found to be 48 mg/kg b. wt and the effective dose was found to be 3 mg/kg. We have observed a significant reduction in the ulcer score in rats pretreated with 3 mg of andrographolide/kg body weight. A favourable increase in the pH and decrease in titrable acidity were observed in the gastric fluid of rats pretreated with the test drug. The gastric tissue H+-K+ ATPase and myeloperoxidase activities were elevated in ulcer-induced animals. The elevation in the enzyme activity was significantly minimized in the andrographolide received animals. The antioxidants and mucin levels were significantly maintained in the gastric tissue of drug-pretreated animals. Andrographolide did not produce any toxic effects in normal rats. This study reveals that the ulcer preventive efficacy of andrographolide may probably due to its antioxidant, cytoprotective and antiacid secretory effects.
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