Biomedical subjects

R Anup

Publications and source records attributed to R Anup.

9 recordsLinked to original sources

PubMed2001

Nitric oxide prevents intestinal mitochondrial dysfunction induced by surgical stress.

BACKGROUND: The intestine is highly susceptible to free radical-induced damage and earlier work has shown that surgical stress induces generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with changes in mitochondrial structure and function. Nitric oxide is an important mediator of gastrointestinal function and this study looked at the effect of nitric oxide on surgical stress-induced intestinal mitochondrial alterations. METHODS: Controls and rats pretreated with the nitric oxide donor L-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine. Enterocytes were isolated, mitochondria prepared and the protection offered by L-arginine against damage due to surgical stress was determined. Protection to structural as well as functional aspects of mitochondria was examined. RESULTS: Mild handling of the intestine affected the enterocyte mitochondrial structure as assessed by lipid composition and electron microscopy. Mitochondria were also functionally impaired with altered calcium flux and decreased respiratory control ratio. Pretreatment with the nitric oxide synthase substrate L-arginine prevented these damaging effects of surgical stress. Protection with arginine was abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, indicating the role of nitric oxide. CONCLUSION: Surgical stress in the small intestine can affect enterocyte mitochondrial structure and function. These damaging effects can be prevented by nitric oxide, an important modulator of cellular function.

Animals↗

PubMed2001

Effect of surgical manipulation of the rat intestine on enterocyte populations.

BACKGROUND: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. One of the mainstays for the maintenance of the integrity of the barrier function is epithelial cell proliferation and migration. The present study looked at the effect of gut manipulation after laparotomy on different cell populations of the intestinal epithelium. METHODS: Surgical manipulation of the gut was performed by opening the abdominal wall and handling the intestine, as is done during laparotomy. Villus and crypt cells were isolated at different time periods after gut manipulation, and mitochondria were prepared from isolated enterocytes. The effects of surgical manipulation on enterocytes and isolated mitochondria were studied. RESULTS: Mechanical manipulation of the gut resulted in alterations in the intestinal epithelium, as shown by decreased cell viability and yield in the crypt cells. The alterations were associated with actin reorganization, as well as with altered cell proliferation and adenosine deaminase activity. At the mitochondrial level, altered mitochondrial function, such as decreased respiratory control ratio, increased 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide reduction, and induction of permeability transition in the crypt cells, was observed. These alterations were maximal 1 hour after surgical manipulation and partially recovered to normal by 24 hours. CONCLUSIONS: Mechanical manipulation of the gut that occurs during any abdominal operation induces alterations in the intestine, both at the cellular and the subcellular levels. The crypt cells bear the brunt of the damage, and the reversibility of the damage is possibly brought about by increased proliferation and movement of the cells.

Actins↗

PubMed2000

Surgical stress and the gastrointestinal tract.

Surgery on any part of the body results in a wide spectrum of alterations in normal body homeostasis. The gastrointestinal tract is extremely sensitive to surgical stress, even at remote locations. It is now evident that the G.I. tract also plays an important role in development of postoperative complications, such as the systemic immune response syndrome and multiple organ failure syndrome. The amount of information available on the cellular and subcellular changes occurring in the gastrointestinal tract after surgical stress is scant. These changes are important since they would act as initiators of tissue damage seen at a later stage, which in turn lead to postoperative complications. This review looks at the information available on the effect of surgical stress on the small intestine, the role of oxygen free radicals in this process, and the changes occurring at the cellular level.

Animals↗

PubMed2000

Surgical stress induces phospholipid degradation in the intestinal brush border membrane.

BACKGROUND: Surgical stress can lead to translocation of bacteria from the intestine into the systemic circulation. The intestinal brush border membrane (BBM) plays an important role in defense against such invasion by luminal bacteria and endotoxin. Our earlier work has shown the development of oxidative stress in the intestine after surgical stress and since the BBM is sensitive to free radical attack, this study examined the effect of surgical stress on the structure and function of intestinal BBM. METHODS: Intestinal BBM were isolated from control and after surgical stress and compared for structural and functional alterations. Surgical stress was also carried out following pretreatment with the xanthine oxidase inhibitor allopurinol or the nitric oxide donor l-arginine, to study the protection offered by these compounds. RESULTS: Surgical stress affected intestinal BBM structure as well as function. A decrease in alkaline phosphatase activity and alpha-tocopherol content, accompanied by an increase in lipid peroxidation, was seen. Surgical stress induced phospholipid degradation with generation of arachidonic acid. Functional impairment with a decrease in glucose transport ability was also seen. These changes are prevented by inhibition of xanthine oxidase by allopurinol pretreatment but not by NO. CONCLUSION: Surgical stress in the small intestine causes structural and functional alterations in the BBM through oxidative stress. This damage could affect gut barrier integrity and generation of arachidonic acid might mediate distal organ dysfunction.

Abdomen↗

PubMed2000

Role of xanthine oxidase in small bowel mucosal dysfunction after surgical stress.

BACKGROUND: The small intestine is highly susceptible to surgical stress even at remote locations. An earlier study using a rat model indicated that oxidative stress plays an important role in this process. The enzyme xanthine oxidase is an important source of free radicals in the small intestine. The role of this enzyme in intestinal damage after surgical stress was examined. METHODS: Rats pretreated with xanthine oxidase inhibitors were subjected to surgical stress by opening the abdomen and handling the intestine, as done during laparotomy. Enterocytes at various stages of differentiation were isolated and the protection offered by xanthine oxidase inhibitors against damage due to surgical stress was determined and compared with normal controls. Protection against ultrastructural changes to the mucosa, as well as mitochondrial function was examined. RESULTS: Surgical stress affected both the villus as well as crypt cells, causing increased superoxide generation, accompanied by increased activity of xanthine oxidase. Xanthine oxidase inhibitors ameliorated the increased superoxide generation, and protected against mitochondrial damage and ultrastructural changes in the intestine. CONCLUSION: Surgical stress affects both the villus and crypt cell populations in the small intestine. The enzyme xanthine oxidase maybe an important mediator of surgical stress in the intestine.

Animals↗

PubMed1999

Apoptotic process in the monkey small intestinal epithelium: I. Association with glutathione level and its efflux.

The apoptotic process in the normal gastrointestinal mucosa is of interest due to its possible role in physiological cell renewal. The aim of this study was to identify the apoptotic process in the monkey small intestine and the association of glutathione level and its efflux in this process. Monkey small intestinal epithelial cells were separated in to different fractions consisting of villus, middle and crypt cells. Apoptosis was identified by DNA ladder pattern and Hoechst staining. The level of glutathione, its efflux and the enzymes involved in its metabolism were quantitated in these fractions. Apoptotic cells were identified predominantly in the villus tip cell fractions by both DNA ladder pattern and Hoechst dye staining. Glutathione level was 7 fold higher in the crypt cells as compared to villus tip cells the middle cells showing a gradual decrease. A similar pattern was seen in mitochondrial content of glutathione. As the cells mature from crypt to villus, there is increased efflux of GSH, which may be responsible for the decreased level of GSH in apoptotic villus cells. In the monkey small intestine, apoptotic cells are seen in the villus tip fractions and the glutathione level and its efflux may play a role in this process.

Animals↗

PubMed1999

Apoptosis in the monkey small intestinal epithelium: structural and functional alterations in the mitochondria.

Our earlier studies have shown apoptosis in the villus tip cells of the monkey small intestinal epithelium. Because mitochondria have been implicated in the apoptotic process, this study looked at the function and lipid composition of mitochondria isolated from apoptotic villus tip cells and compared it with middle and crypt cells. Decreased MTT reduction and respiratory control ratio, increased swelling and altered mitochondrial enzyme activities were seen in the villus tip cell mitochondria when compared to other cells. The lipid composition of the villus tip mitochondria were different from the other mitochondria. A decrease in phosphatidylethanolamine and phosphatidyl-inositol and an increase in phosphatidic acid was seen in these mitochondria. Fatty acid composition analysis showed more unsaturated fatty acids in the free fatty acid and phospholipid fraction in villus tip cell mitochondria as compared to other cells. These studies suggest that in the monkey small intestinal epithelium, apoptotic process is associated with functional and structural alterations in the mitochondria.

Adenosine Triphosphatases↗

PubMed1999

Surgical stress and the small intestine: role of oxygen free radicals.

BACKGROUND: Any surgical procedure can be associated with altered intestinal function. The mechanism involved in these changes at the cellular level during surgical stress has not been worked out. This study looked at the biochemical and functional alterations, along with ultrastructural changes, in the intestine during surgical stress in a simple rat model. METHODS: Surgical stress was induced by opening the abdominal wall and handling the intestine as during laparotomy. The effect of oxidative stress on the enterocyte and altered intestinal permeability as well as the ultrastructural changes to the mucosa were studied. RESULTS: Surgical stress results in oxidative stress on enterocytes, as evidenced by increased xanthine oxidase and decreased catalase activity along with altered thiol redox status. This was associated with increased intestinal permeability and widened intercellular spaces. These changes were prominent at 60 minutes after laparotomy and returned to normal by 24 hours. CONCLUSIONS: Mild intestinal handling is capable of inducing oxidative stress in enterocytes; this could be one of the mechanisms by which intestinal mucosal alterations occur during surgical stress.

Animals↗

PubMed1999

Enterocyte mitochondrial dysfunction due to oxidative stress.

The endogenous production of H2O2 in isolated rat intestinal mitochondria and oxidant induced damage to mitochondria were examined. There was an appreciable amount of H2O2 production in presence of succinate, glutamate and pyruvate, while the presence of rotenone with succinate further increased production. Superoxide generated by the X-XO system induced membrane permeability transition (MPT), calcium influx, lipid peroxidation and changes in membrane fluidity in mitochondria. A decreased mitochondrial ATPase activity and uncoupling of respiration was also observed. Spermine inhibited swelling induced by X-XO and also blocked the calcium influx and reversed the membrane fluidity changes.

Animals↗