Studies on the antiulcerogenic and antihepatotoxic potential of Chitosan and Glucosamine in experimental rats

The present study examined the antiulcer effect of glucosamine on mucosal antioxidant defense system in ibuprofen-induced peptic ulcer in male albino rats. The number of lesions in the gastric mucosa, volume of gastric juice, acid output, pepsin activity, lipid peroxides, reduced glutathione content, the activities of glutathione dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (catalase and superoxide dismutase), activities of membrane bound ATPases, protein content, glycoprotein components, minerals status, SDS-PAGE electrophoretic pattern of mucosal protein, amino acid composition and histopathology were determined. Prior oral administration of chitosan and glucosamine significantly prevented the ibuprofen-induced increases in the number of lesions in the gastric mucosa, volume of gastric juice and acidity. They also maintained the activity of pepsin at near normal level. Oral pretreatment of chitosan and glucosamine exerted a significant antioxidant effect by preventing ibuprofen-induced lipid peroxidation and by maintaining the level of reduced glutathione and the activities of mucosal antioxidant enzymes at near normalcy. Prior oral administration of glucosamine significantly prevented the ibuprofen-induced depletion of protein and glycoprotein components and maintained the activities of membrane bound ATPases as compared to untreated ulcer induced group of rats. Amino acid composition and mineral status were also brought to the near normal level in the chitosan and glucosamine pretreated groups. The antiulcerogenic activity of glucosamine might be ascribable to its ability to neutralize the hydrochloric acid secreted into the stomach and to its capability to strengthen the mucosal barrier by increasing mucosal glycoprotein synthesis and to its free radical scavenging property. Histopathological investigations and amino acid observations of the mucosal tissue were also supported the antiulcerogenic effect of chitosan and glucosamine. The antioxidant capacity of chitosan and glucosamine to inhibit ibuprofen-induced lipid peroxidation is also supportive to the antiulcer effect. Tuberculosis is a dangerous disease and its death toll is increasing year by year. Intake of isoniazid and rifampicin, the most common antitubercular drugs, lead to fatal hepatotoxic condition. I have studied the protective effect of chitosan and glucosamine supplementations against the hepatotoxicity induced by antitubercular drugs with respect to the changes in the levels of protein, SDS PAGE-electrophoretic pattern protein, levels of diagnostic marker enzymes, lipid components, lipid peroxidation, albumin, globulin, albumin/globulin ratio, glucose, creatinine and urea in the serum and diagnostic marker enzymes, hepatic thiols, lipid components, lipid peroxidation, reduced glutathione, the activities of glutathione dependent antioxidant enzymes and antiperoxidative enzymes, activities of membrane bound ATPases, protein content, glycoprotein components, minerals status, glycoprotein conjugates, electrophoretic pattern of protein, fatty acid composition and histopathology in the liver tissue of normal and experimental groups of rats. Co-administration of chitosan and glucosamine was found to prevent significantly the antitubercular drugs-induced changes in the levels of diagnostic marker enzymes and albumin/globulin ratio in experimental groups of rats. Isoniazid and rifampicin-induced lipid peroxidation was also found to be prevented by the administration of chitosan and glucosamine. The oral administration of antitubercular drugs caused a significant elevation in the levels of diagnostic marker enzymes and cholesterol, triglycerides, free fatty acids and lipid peroxidation in serum and liver of experimental rats. There was a slight decline in the level of phospholipids in liver tissue also observed. Chitosan and glucosamine exerted a significant antilipidemic effect against isoniazid and rifampicin-induced hepatitis by maintaining the levels cholesterol, triglycerides, free fatty acids and phospholipids in serum and liver at near normalcy. Further, chitosan administration maintained the levels of lipid peroxides, glucose, creatinine, albumin/globulin, urea, hepatic thiols and protein to normalcy in experimental groups compared to hepatotoxicity-induced group of rats. Levels of glycoconjugates were also maintained to near normal level by chitosan and glucosamine co-administration. From the results obtained, it can be concluded that co-chitosan and glucosamine are beneficial against antitubercualr drugsinduced hepatoxicity. SDS page electrophorectic pattern, fatty acid composition and histopathological observations also support this finding. LIST OF TABLES Table Title Table 2.1 Chitin content in various sources Table 4.1.1 Number of lesions, volume of gastric juice, and acid output and pepsin activity of the gastric mucosa of normal and experimental groups of rats Table 4.1.2 Activities of membrane bound ATPases of the gastric mucosa of normaland experimental groups of rats Table 4.1.3 Levels of reduced glutathione and lipid peroxides in the gastric mucosa of normal and experimental groups of rats Table 4.1.4 Activities of antioxidant enzymes in the gastric mucosa of normal and experimental groups of rats Table 4.1. 5 Mineral status of the stomach of normal and experimental groups of rats Table 4.1. 6 Levels of various amino acids in the stomach of normal and experimental groups of rats Table 4.2.1 Levels of diagnostic marker enzymes in the serum of normal and experimental groups of rats Table 4.2.2 Levels of urea, albumin, globulin, albumin/globulin ratio in the serum of normal and experimental groups of rats Table 4.2.3 Levels of creatinine and glucose in the serum of normal and experimental Table 4.2.4 Levels of glycoconjugates in the liver of normal and experimental groups of rats Table 4.2.5 Levels of lipid peroxides in the serum and liver of normal and experimental groups of rats Table-4.2.6 Levels of antioxidant enzymes in the liver of normal and experimental groups of rats Table 4.2. 7 Activities of membrane bound ATPases in the liver of normal and experimental groups of rats Table 4.2. 8 Levels of total thiols and free thiol in the liver of normal and experimental groups of rats Table 4.2. 9 Levels of lipid components in the serum or normal and experimental groups of rats Table 4.2.10 Levels of lipid components in the liver normal and experimental groups of rats Table 4.2.11 Fatty acid composition of the liver of normal and experimental groups of rats Table 4.2.12 Levels of calcium, magnesium and zinc in the liver of normal and experimental groups of rats LIST OF FIGURES Figure Title Fig.2.1. Structure of chitosan Fig.2.1. Structure of I3-D-Glucosamine Fig.2.3. Structure of stomach Fig.2.4. Helicobacter pylori Fig.2.5. Structure of ibuprofen Fig.2.6. Fig. 2.6. The Cyclooxygenase Pathway Fig.2. 7. Structure of isoniazid Fig.2. B. Metabolic pathway of Isoniazid Fig.2. 9. Structure of rifampicin Fig.4.1.1. Levels of mucosal protein in experimental and normal rats. Fig.4.1.2. Levels of hexose and hexosamine in the stomach tissue of control and treated animals. Fig.4.1.3. Sialic acid levels in the stomach of normal and experimental groups of rats. Fig.4.1.4. Levels of sodium and potassium in the stomach of normal and experimental groups of rats. Fig.4.2.1. Levels of AL T and AST in the liver of normal and experimental groups of rats. Fig.4.2.2. Levels of protein in the serum of normal and experimental groups of rats. Fig.4.2.3. Protein levels in the liver of normal and experimental rats. Fig.4.2.4. Levels of HDL-cholesterol and LDL-cholesterol in the serum of normal and experimental groups of rats. Fig.4.2.5. Levels of sodium and potassium in the liver of normal and experimental groups of rats.