Effect Of Oxidative Stress On Gastrointestinal Structure And Function In Animal

Gastrointestinal tract is main digestive, absorbtive and metabolic organ in animal. It is difficult to be conscious of gastrointestinal disfunction induced by moderate stress, Oxidative stress of gastrointestinal mucosa is involved in inflammatory bowel disease, and appropriate antioxidant may modulate intestinal redox status. The aim of our experiment was to study the effect and regulation mechanism of free radical and antioxidant on gastrointestinal growth, structure, function, hormone exudation and expression of gene.1. Oxidative injury of free radical on the rat IECs, and protection by GSH in vitroThe objective of the this study was to investigate the direct oxidative injury of the different dose xanthine and xanthine oxidase (X/XO) on rat intestinal epithelial cells (IECs), and protection by glutathione(GSH)in vitro. IECs were maintained in culture medium for 72 h. Subsequently, culture cells were divided into 7 groups, and cultured in the presence and absence of xanthine (10μmol/L), xanthine oxidase (10, 40, 70 U/L) or GSH (1.5μmol/ml) for 24h. The oxidative injury of reactive oxygen species on IECs were evaluated by studying production of malondialdehyde (MDA), DNA fragmentation, total antioxidant capacity (TRAP), proliferation, activity of superoxide dismutase (SOD) and catalase (CAT), the level of Ca2+ and apoptosis of IECs. The results show the proliferation of IECs was significantly inhibited, but the activity of SOD and the value of total antioxidant capacity (TRAP) was slightly increased at low activity of XO (10U/L). However, the oxidative stress significantly inhibited cell proliferation, decreased TRAP, increased lipid peroxidation, concentration of Ca2+ and DNA fragment at XO (40,70 U/L). Both of DNA fragment and apoptosis of IECs increased gradually with the increase of XO concentration (P<0.05). Presence of GSH remarkably enhanced TRAP value (P<0.05), but failed to affect the activity of SOD corresponding X/XO (10 U/L) alone-treated. The reduction in lipid peroxidation and DNA damage and the increase in cell proliferation were also observed in IECs. These results strongly suggest that IECs exposed to X/XO could induce its oxidative stress and injury, GSH could provide significant protection against oxidative injury of IECs by scavenging ROS in vitro. Moderate oxidative stress might selectively stimulated the synthesis of antioxidant enzyme, but significantly decreased cell proliferation.2. Regulation of of CS on IND-induced gastric oxidative injury and energy metabolism in ratsTo study the gastroprotective effect of cysteamine (CS) on indomethacin-induced gastric ulcers in rats. A total of 45 male, SD rats weighing 180–220 g, have been used for the experiments. The Forty-five were randomly divided into three groups of 15 each:Control (A), stress (B) oral Indomethacin (IND, 45mg/kg weight); antioxidation (C), oral IND (45mg/kg weight) after oral CS (100mg/kg weight) for 1h. The concent of endogenous prostaglandin E2 (PGE2), the changes of ulcer index, the activities of H+,K+-ATPase and XO, the antioxidative index, the expressions of iNOS mRNA, somatostatin (SS) and the size of adenylic acid pool(ATP, ADP, AMP) in gastric mucosa tissue or mitochondria at postinjury 6, 12, 24h. The results showed that gastric lesions were significantly reduced by CS as compared with the group B. IND significantly damaged gastric mucosa excretive function and integrality, decreased the levels of SOD, glutathione (GSH) and the size of adenylic acid (AMP, ADP, ATP) in gastric mucosal mitochondria. However, CAT and lipid peroxidation (LPO) were increased corresponding the control (P< 0.05). The administration of CS reversed the trend, inducing a significant increase of SOD, GSH and total adenylic acid, a reduction of LPO and SS in gastric mucosa, and inhibitied the expressions of iNOS mRNA compared to the group B. Based on above results, it was concluded that the oxidative stress damged gastric normal structure and function, furthermore induced gastric energy metabolism disfunction. Gastroprotective effect of cysteamine can be attributed to its reducing effect on the oxidative damage.3. Regulation of oral iron on the intestinal structure and function in piglets with DSS -induced colitisTo estimate the effect of oral iron on the intestinal function and oxidative redox status in piglets with dextran sulphate sodium (DSS)-induced colitis, fifty 21-day-old weaned piglets with an average initial weight of 4.80±0.76kg were randomly divided into five groups of ten each. The piglets received regular diet and water, or four diets with 0, 0.03, 0.2 or 1% FeSO4·2H2O and water with 4% DSS, respectively, for 10 days. Growth performance, digestibility, intestinal microflora, permeability, absorptive capacity, lipid peroxidation, free radical, antioxidation index and intestinal structure of piglet were determined. We observed oral iron induced oxidative stress in colonic mucosa, and a markedly higher lactulose/mannitol (Lac/Man) excretion ratio and lower serum concentration of D-xylose in Fe 0.2 and 1% supplementated piglets than piglets on DSS alone, but not in Fe 0.03% supplemented piglets. Supplementation of oral iron resulted in intestinal villus injury in piglets, and dose-response manner. The activities of SOD, CAT and glutathione peroxidase (GPx) significantly increased in the DSS group compared with the control group (P< 0.05). Iron supplementation significantly decreased the activities of GPx and CAT, as was vitamin E content, but not SOD. Furthermore, excess iron significantly increased the production of MDA and hydroperoxides (HP), in a dose-response related manner. In conclusion, excess iron supplementation caused injury on intestinal mucosa in piglets with colitis, these might be involved in the antioxidant defence system weaken in condition which the oxidative stress was stronger and sustained. Thus, lower iron supplementation in diarrhetic and iron-deficient piglets might be beneficial.4. Effect of high-caloric feeding on peptic growth, function and redox of pigletA total of 30 weaned piglets of an average initial body weight of 5.53±0.53kg, weaned at 21±2 day of age, were allocated to three dietary treatments of ten each in a randomized complete block design. 1) control group: regular diet; 2) 5% grease; 3) 10% grease. The piglets were fed the respective diets for 21 days. To study the mechanism and effect of the high caloric feeding-induced chronic stress on the growth performance, digestibility, the weight of peptic and intestinal mucosa; the content of MDA, total cholesterol (TC), total glycerol(TG) and cortisol in serum, activities of SOD and digestive enzyme, the expression of GHr and IGF-1 were determined. The results showed that 5% grease significantly increased the performance of piglets when compared with the piglets on control diet (P<0.05), but not in 10% gaease group (P>0. 05). Different dose of grease didn't increase significantly the intestinal weight and the activity of lipase, but not in protease and the weight of other peptic; on the contrary, administration of 10% grease decreased the weight of intestinal mucosa. The level of TC and TG increased with the development of additive grease. The digestibility of CP and EE were increased in the 5% grease group when compared with the 10% grease group, so was the expression of GHR mRNA. However, 10% grease significantly increased the level of cortisol and MDA in serum, reduced activity of SOD and expression of GHR mRNA. Addition of grease had no effect on the expression of IGF-1 mRNA in intestinal mucosa. In conclusion, the high-caloric feeding could cause chronic stress in piglets, induce considerable gastrointestinal side effects, in a time-response related manner.