Biliary glutathione promotes the mucosal metabolism of luminal peroxidized lipids by rat small intestine in vivo.

Aw, Tak Yee

doi:10.1172/jci117439

Cited by 58 publications

(48 citation statements)

References 31 publications

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“…Normal concentrations of intracellular GSH are maintained by de novo synthesis, regeneration from GSSG or through import via the Na + -dependent transport system. GSH transport into the cell is demonstrated in several cell types, including enterocytes (Aw, 1994;Mårtensson et al, 1990). The ability of enterocytes to import luminal GSH is important for the intestinal thiol balance, especially in pro-oxidative conditions, since the human diet is extremely various concerning the GSH and LOOH content.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant status of the celiac mucosa: implications for disease pathogenesis

Stojiljković¹,

Kasapović²,

Pejić³

et al. 2012

Celiac Disease - From Pathophysiology to Advanced Therapies

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Section: Discussionmentioning

confidence: 99%

Antioxidant status of the celiac mucosa: implications for disease pathogenesis

Stojiljković¹,

Kasapović²,

Pejić³

et al. 2012

Celiac Disease - From Pathophysiology to Advanced Therapies

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“…Recent strategies to improve intestinal structure and function during malnutrition have included supplementing specific nutrients, e.g., glutamine, increasing the supply of antioxidants to protect against oxidative injury, and adding factors to stimulate cell growth (32)(33)(34). Because oxidative stress may play a role in gastrointestinal injury, and malnutrition reduces the antioxidant defense in the gut and disrupts the intestinal architecture, we investigated the involvement of mucosal integrity, mucin production and secretion, and antioxidant defense in the intestinal dysfunction due to chronic diarrhea leading to proteinenergy malnutrition, as well as the possible reparative effect of feeding diets supplemented with different sources of PUFA on intestinal repair.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Polyunsaturated Fatty Acids to Intestinal Repair in Protein-Energy Malnutrition

et al. 2007

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The aim of this study was to assess the effect of polyunsaturated fatty acids supplied in the diet on intestinal mucosa repair in a rat model of protein-energy malnutrition. Rats were fed either a standard semipurified diet or the same diet containing lactose as the only source of carbohydrate to cause protein-energy malnutrition. Diarrhea was induced within 24 h and was maintained for 2 weeks, after which both groups of rats were fed for 1 week either the standard diet or the standard diet supplemented with different sources of fatty acids, such as olive oil (OO), fish oil (FO), and purified phospholipids from pig brain (BPL). The lactose-enriched diet caused loss of enterocyte microvilli, lymphocyte infiltration, supranuclear cytoplasmic vesiculation, decreased number of goblet cells, low-density enlarged mitochondria, and less cristae. The FO diet improved the pathology score according to the histological and ultrastructural analysis, with an increased number of goblet cells, ratio of microvilli length to crypt depth, and percentage of intraepithelial lymphocytes compared to those found in rats with protein-energy malnutrition. We previously reported that chronic diarrhea depletes the antioxidant defense in rat intestine; we now show that both, the FO and the BPL diets, increase GSH levels in colon and that some antioxidant enzyme activities vary according to the source of fatty acids, with higher catalase and superoxide dismutase by the FO diet in jejunum, increased catalase by the BPL diet in jejunum, and elevated glutathione peroxidase by the OO diet in colon. The fatty acid profile of intestinal mucosa reflects the source of fat in the diet, with the lowest ratio of n-6/n-3 for rats fed the FO diet. These results suggest that dietary polyunsaturated fatty acids, particularly those in the n-3 series, may play an important role in intestinal repair in chronic diarrhea due to protein-energy malnutrition.

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“…failure to secrete GSH in bile might be predicted to cause intestine mucosal GSH to fall, as has been described with bile duct ligation. 9 In addition, considering that bile GSH is hydrolyzed in the intestine and amino acid constituents are absorbed, failure to secrete GSH may have systemic conseAbbreviations: EHBR, Eisai hyperbilirubinemic rat; GY, Groningen Yellow; TR 0 , transport-deficient; GSH, reduced glutathione; RcGshT, rat canalicular reduced glutathione quences (e.g., lowering of kidney GSH levels). In this study, transporter; GCS, g-glutamylcysteine synthetase; mBCl, monochlorobimane; cDNA, comwe examined these alternative mechanisms for increased cell plementary DNA; SDS, sodium dodecyl sulfate; GCS-HS, heavy subunit of GCS; ATP, GSH and the organ specificity of these changes.…”

Section: Eisai Hyperbilirubinemic Rats (Ehbr) Are Mutant Eisai Hyperbmentioning

confidence: 99%

“…9 Bile duct liga-EHBR exhibited a similar marked increase in liver GSH tion leads to a 50% fall in intestinal GSH. 9 To our surprise, levels as GY/TR 0 mutants.…”

mentioning

confidence: 94%

“…9 Bile duct liga-EHBR exhibited a similar marked increase in liver GSH tion leads to a 50% fall in intestinal GSH. 9 To our surprise, levels as GY/TR 0 mutants. 1 We found an increase in GCS intestinal GSH was increased in EHBR, and this effect was activity and cysteine concentration in EHBR livers, two of the widespread, including kidney, which presumably reflects a most important parameters in determining GSH synthesis generalized up-regulation of GSH synthesis.…”

mentioning

confidence: 94%

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Alterations in Glutathione Homeostasis in Mutant Eisai Hyperbilirubinemic Rats

Cai

Kuhlenkamp

et al. 1996

Hepatology

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Eisai hyperbilirubinemic rats (EHBR) are mutant Eisai hyperbilirubinemic rats (EHBR) are mutantSprague-Dawley rats (similar to the Groningen Yellow (GY)/ Sprague-Dawley rats that exhibit impaired biliary ortransport-deficient (TR 0 ) mutant Wistar rats) characterized ganic anion and reduced glutathione (GSH) secretion. In by an inherited defect in organic anion secretion into bile. [1][2][3][4] addition, liver GSH levels are twice that of age-matched Both mutants resemble the human Dubin-Johnson syndrome controls. The mechanisms for the defect in biliary GSH and exhibit impaired biliary secretion of organic anions, such secretion and the increase in cell GSH are not fully unas conjugated bilirubin, sulfobromophthalein-reduced glutaderstood. We previously showed that canalicular memthione (GSH) conjugate, and sulfated and glucuronidated bile brane-enriched vesicles isolated from EHBR livers exacids. [1][2][3][4] In addition, biliary GSH excretion is also severely hibited normal GSH transport. In the present study, we impaired in both mutants when examined in vivo or in perexamined the steady-state rat canalicular reduced glutafused livers. [1][2][3] The mechanism for the impairment in biliary thione transporter (RcGshT) messenger RNA (mRNA)GSH secretion has been a subject of controversy. While Oude and protein levels, as well as the mechanisms for the Elferink et al. suggested the defect is a direct effect of the increase in cell GSH. Both Northern and Western blot mutation, 1 we demonstrated normal GSH transport in canaanalyses of EHBR livers showed nearly identical licular membrane-enriched vesicles isolated from EHBR livRcGshT mRNA and polypeptide levels, respectively, as ers, 2 which supports an indirect or secondary effect of the compared with controls. Treatment with phenobarbital, mutation. Because our laboratory recently cloned the rat canwhich increased steady-state RcGshT mRNA by five-to alicular reduced glutathione transporter (RcGshT), 5 possible sixfold, RcGshT polypeptide, and biliary GSH secretion altered expression of RcGshT secondary to the mutation in by onefold in controls, had a smaller effect on steady-EHBR can now be examined. state RcGshT-mRNA level in EHBR (by 1.5-fold) and did Normally, hepatic GSH level is maintained by a balance not increase RcGshT polypeptide or biliary GSH secrebetween synthesis and efflux, 6 about half of which is biliary tion. In examining possible mechanisms for increased in mature rats. 7 GSH synthesis rates are governed by the liver GSH, both cysteine level and g-glutamylcysteine availability of cysteine and the activity of the rate-limiting synthetase (GCS) activity were significantly higher than enzyme, g-glutamylcysteine synthetase (GCS), which, in controls, while the activity of GSH synthetase was unturn, is regulated physiologically by feedback-competitive inchanged. Northern and Western blot analyses also hibition by GSH (K i Å 2.3 mmol/L). 6,8 In GY/TR 0 mutants, showed increased steady-state GCS heavy subunit (GCSliver GSH levels are twice that of age-mat...

show abstract

Biliary glutathione promotes the mucosal metabolism of luminal peroxidized lipids by rat small intestine in vivo.

Cited by 58 publications

References 31 publications

Antioxidant status of the celiac mucosa: implications for disease pathogenesis

Antioxidant status of the celiac mucosa: implications for disease pathogenesis

Contribution of Polyunsaturated Fatty Acids to Intestinal Repair in Protein-Energy Malnutrition

Alterations in Glutathione Homeostasis in Mutant Eisai Hyperbilirubinemic Rats

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