The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted.

In vitro effect of N-acetyl-L-cysteine on glutathione and sulfhydryl levels in X-linked adrenoleukodystrophy patients

Introduction: Recent evidence shows that oxidative stress seems to be related with the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), a neurodegenerative disorder. Methods: In the present study, the in vitro effect of N-acetyl-L-cysteine (NAC) on glutathione (GSH) and sulfhydryl levels in X-ALD patients was evaluated. Results: A significant reduction of GSH and sulfhydryl content was observed in X-ALD patients compared to the control group. Furthermore, 5 mM of NAC, in vitro, led to an increase in GSH content and sulfhydryl groups in these patients. Conclusion: These data probably indicate that an adjuvant therapy with the antioxidant NAC could improve the oxidative imbalance in X-ALD patients(AU)

Opioid peptides and gastrointestinal symptoms in autism spectrum disorders

Autism spectrum disorders (ASDs) are characterized by deficits in the individual’s ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.

Burnout syndrome among undergraduate nursing students at a public university / Síndrome de Burnout entre estudantes de graduação em enfermagem de uma universidade pública / Síndrome de Burnout entre estudiantes de pregrado en enfermería de una universidad pública

OBJECTIVE: to investigate the burnout syndrome and its relationship with demographic and academic variables among undergraduate nursing students at a public university in Southern Brazil. METHOD: a quantitative study with 168 students, by applying an adaptation of the Maslach Burnout Inventory - Student Survey, validated for this study. We used descriptive and variance analysis of the data analysis. RESULTS: we found that students do not have the burnout syndrome, manifesting high average scores in Emotional Exhaustion, low in Disbelief and high in Professional Effectiveness; that younger students who perform leisure activities have greater Professional Effectiveness, unlike students in early grades with no extracurricular activities; combining work and studies negatively influenced only the Professional Effectiveness factor, while the intention of giving up influenced negatively Disbelief and Professional Effectiveness factors. CONCLUSION: the situations that lead students to Emotional Exhaustion need to be recognized, considering the specificity of their study environments. .

OBJETIVO: investigar a síndrome de Burnout e sua relação com variáveis sociodemográficas e acadêmicas, entre estudantes de graduação em enfermagem de uma universidade pública do Sul do Brasil. MÉTODO: estudo quantitativo, realizado com 168 estudantes, mediante a aplicação de uma adaptação do Maslach Burnout Inventory - Student Survey, validada para este estudo. Utilizou-se a análise descritiva e de variância para análise dos dados. RESULTADOS: constatou-se que os estudantes não apresentam a síndrome de Burnout, manifestando médias altas em exaustão emocional, baixas em descrença e altas em eficácia profissional; que estudantes mais jovens e que realizam atividades de lazer apresentam maior eficácia profissional, diferentemente de estudantes das séries iniciais e que não realizam atividades extracurriculares; conciliar trabalho e estudos influenciou negativamente apenas o fator eficácia profissional, enquanto a intenção de desistir do curso influenciou negativamente os fatores descrença e eficácia profissional. CONCLUSÃO: faz-se necessário o reconhecimento das situações que levam os estudantes à exaustão emocional, considerando a especificidade de seus ambientes de formação. .

OBJETIVO: investigar la síndrome de burnout y su relación con variables sociodemográficas y académicas, entre estudiantes de pregrado en enfermería de una universidad pública del Sur de Brasil. MÉTODO: estudio cuantitativo, desarrollado con 168 estudiantes, mediante la aplicación de una adaptación del Maslach Burnout Inventory - Student Survey, validada para fines de ese estudio. Fueron utilizados los análisis descriptivo y de variancia para analizar los datos. RESULTADOS: se constató que los estudiantes no presentan la síndrome de burnout, manifestando altos promedios en Agotamiento Emocional, bajos en Descreencia y altos en Eficacia Profesional; que estudiantes más jóvenes y que practican actividades de ocio presentan mayor Eficacia Profesional, diferentemente de estudiantes de los años iniciales sin actividades extracurriculares; conciliar trabajo y estudios influyó negativamente apenas el factor Eficacia Profesional, mientras la intención de desistir del curso influyó negativamente los factores Descreencia y Eficacia Profesional. CONCLUSIÓN: es necesario reconocer las situaciones que llevan a los estudiantes al Agotamiento Emocional, considerando la especificidad de sus ambientes de formación. .

Indicators of oxidative stress in thyroid cancer.

Ferric reducing antioxidant power (FRAP), myeloperoxidase (MPO) activity and the levels of protein thiols and carbonyls were estimated in the blood samples of thyroid cancer patients (n = 20) before and after thyroidectomy, as well as in healthy controls (n = 10) to study the extent of damage caused by tumor tissue proliferation-induced oxidative stress and to ascertain that oxidative stress levels drop, when there was no proliferation. A significant decrease (p<0.001) in the levels of serum protein thiols and FRAP as well as a significant increase (p<0.001) in the levels of protein carbonyls and MPO activity in the blood of thyroid cancer patients before surgery was observed as compared to healthy controls. All the parameters studied also showed a significant difference (p<0.001) in their respective levels in thyroid cancer patients, pre- and post-thyroidectomy. These findings present the role of oxidative stress as a pathological implication of thyroid cancer.

Assessment of free radical-mediated damage in head and neck squamous cell carcinoma patients and after treatment with radiotherapy.

Reactive oxygen species (ROS) produced as a part of cellular metabolism can interact with biological macromolecules such as DNA, proteins and lipids and interfere with their normal functions, leading to the loss of cellular viability. ROS have been implicated in many pathophysiological conditions including cancer. In the present study, the damage caused by ROS and the effect of radiation in head and neck squamous cell carcinoma (HNSCC) patients were assessed in the erythrocytes by analyzing the superoxide dismutase (SOD) and catalase (CAT) activities, and levels of total thiols (T-SH) and malondialdehyde (MDA, a marker for lipid peroxidation). Blood samples were collected before the start of treatment and after the completion of radiotherapy. Both SOD and CAT activities were decreased in untreated patients, but elevated in patients after treatment. The T-SH levels were also depleted in untreated HNSCC patients, but elevated non-significantly after radiation therapy (p>0.05). The levels of MDA showed a significant increase in both untreated patients and after radiation therapy when compared with normal subjects (p<0.05). Thus, the present study indicated that the free radical-mediated damage was aggravated in untreated HNSCC patients, but the levels of antioxidants returned to baseline or nearly so after the treatment with radiation therapy.

Therapeutic role of L-arginine on free radical scavenging system in ischemic heart diseases.

Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina.

Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment: [review]

Human serum albumin (HSA) is the most abundant protein in the intravascular compartment. It possesses a single thiol, Cys34, which constitutes ~80 percent of the total thiols in plasma. This thiol is able to scavenge plasma oxidants. A central intermediate in this potential antioxidant activity of human serum albumin is sulfenic acid (HSA-SOH). Work from our laboratories has demonstrated the formation of a relatively stable sulfenic acid in albumin through complementary spectrophotometric and mass spectrometric approaches. Recently, we have been able to obtain quantitative data that allowed us to measure the rate constants of sulfenic acid reactions with molecules of analytical and biological interest. Kinetic considerations led us to conclude that the most likely fate for sulfenic acid formed in the plasma environment is the reaction with low molecular weight thiols to form mixed disulfides, a reversible modification that is actually observed in ~25 percent of circulating albumin. Another possible fate for sulfenic acid is further oxidation to sulfinic and sulfonic acids. These irreversible modifications are also detected in the circulation. Oxidized forms of albumin are increased in different pathophysiological conditions and sulfenic acid lies in a mechanistic junction, relating oxidizing species to final thiol oxidation products.

Arsenic induces oxidative stress, sphingolipidosis, depletes proteins and some antioxidants in various regions of rat brain.

OBJECTIVES: To seek an interrelationship, if any, between oxidant stress and neurochemical changes in various rat brain regions after arsenic exposure. MATERIALS AND METHODS: This study was carried out at the Department of Biochemistry, Al Arab Medical University, Benghazi, Libya. Seventy five male Spraque-Dawley rats were divided into three groups: CONTROL GROUP: Rats were administered 2 ml of normal saline solution/kg body weight (b.wt.) daily for 20 days by intraperitoneal (i.p.) route. ARSENIC-TREATED GROUP: Rats received elemental arsenic (as sodium arsenate) 2.0 mg/kg b.wt. daily for 20 days by i.p. route. RECOVERY GROUP: Rats received 2.0 mg/kg b.wt. elemental arsenic daily for 20 days by i.p. route and were allowed to recover for 20 days. Rats were sacrificed and brains were dissected into cerebral cortex, corpus striatum, cerebellum and brain stem. Tissue homogenized in respective mediums. And were analyzed for lipid classes, oxidative stress, concentration of proteins, glutathione and ascorbic acid by utilizing standard colorimetric procedures. RESULTS: Arsenic exposure increased the oxidant stress because lipid peroxidation was enhanced. And decreased the contents of lipid classes, proteins, glutathione and the ascorbic acid in various rat brain regions. However, thins-layer chromatography exhibited regional variations in phospholipids classes. CONCLUSION: These results suggested that arsenic-initiated oxidant stress by increasing lipid peroxidation. The losses of lipid classes, ascorbic acid and glutathione may be attributed to peroxidative damage and binding of arsenic with sulfhydryl groups of enzymes. Recovery of animals showed reversibility in most of studied parameters, but gangliosides and cerebrosides over shooted. And speculated "Sphingolipidosis". It is then likely that repeated exposures of humans to arsenic may result in hampering of cell signalling, apoptosis and mutagenesis.

Differential Effect of gamma-radiation-induced Heme Oxygenase-1 Activity in Female and Male C57BL/6 Mice

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body gamma-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax gamma-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to gamma-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of gamma-irradiation on anti-oxidant system in female and male mice.

Antiinflammatory and antiulcer activities of phytic acid in rats.

Maximum antiinflammatory activity of phytic acid (PA) was seen at an oral dose of 150 mg/kg in the carrageenan induced rat paw edema model. Although PA showed ability to prevent denaturation of proteins, it showed less antiinflammatory activity than ibuprofen. Ability of PA to bring down thermal denaturation of proteins might be a contributing factor in the mechanism of action against inflammation. PA, at all the doses tested, showed significant protection from ulcers induced by ibuprofen, ethanol and cold stress, with a maximum activity at 150 mg/kg. There was a significant increase in gastric tissue malondialdehyde levels in ethanol treated rats but these levels decreased following PA pretreatment. Moreover, pretreatment with PA significantly inhibited various effects of ethanol on gastric mucosa, such as, reduction in the concentration of nonprotein sulfhydryl groups, necrosis, erosions, congestion and hemorrhage. These results suggested that gastro-protective effect of PA could be mediated by its antioxidant activity and cytoprotection of gastric mucosa.

Sulfhydryl modification affects coronary artery tension by changing activity of delayed rectifier K+ current

It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.

Ischemic preconditioning reduces peripheral oxidative damage associated with brain ischemia in rats

Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be important for their clinical outcome. In the present investigation we studied tert-butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10-min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min), followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death in rats and gerbils submitted to a lethal (10 min) ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min) and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH) groups significantly contribute to the antioxidant capacity of plasma. There was a significant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along with brain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the preconditioning phenomenon

Human lens epithelial layer in cortical cataract.

Normal and cataractous human eye lenses were studied by morphology and protein analysis. A marked decrease in protein sulfhydryl (PSH) and nonprotein sulfhydryl (NSPH) was observed in nuclear and cortical cataractous epithelia. Moreover, decrease in PSH contents and an increase in insoluble proteins were found to be correlated only in cortical cataractous epithelium which is also accompanied by various morphological abnormalities. In nuclear cataractous epithelium, however, there was very little insolubilisation of proteins. The epithelial morphology in nuclear cataracts was almost similar to normal lens epithelium. Hence, it is assumed that the protein insolubilisation and various morphological abnormalities are characteristics of cortical cataractous epithelium. This leads us to believe that opacification in cortical cataract might initiate in the epithelial layer.

Effect of enterotoxin on glutathione status in the intestinal mucosa.

The effect of luminal exposure of enterotoxins on the intestinal mucosal glutathione (GSH) was studied in rat. Cholera toxin induced fluid secretion and decreased mucosal GSH by 35% without altering oxidized glutathione (GSSG) level. Toxin induced fluid secretion was tested after mucosal GSH depletion by compounds such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) and thiol supplementation with N-Acetyl cysteine (NAC). Fluid secretion was not altered by prior thiol depletion or supplementation. Exposure of intestinal lumen to bacterial endotoxin resulted in 25% decrease in mucosal GSH with two fold increase in GSSG. Luminal exposure of Shiga toxin did not alter the mucosal thiol. The level of other low molecular weight thiols, cysteine and cystine was not altered by luminal exposure of any of these toxins. These results show that although cholera toxin decreased the mucosal GSH level, prior modulation of thiol status of the mucosa may not have any effect on toxin-induced fluid secretion.

Natural honey exerts its protective effects against ethanol-induced gastric lesions in rats by preventing depletion of glandular nonprotein sulfhydryls.

The role of nonprotein sulfhydryls (NP-SH) in the protective effects of honey against absolute ethanol-induced gastric lesions was studied in rats. Sucralfate and ranitidine were used as known standard gastroprotective agents. Honey orally and drugs orally or subcutaneously were administered to 24 h fasted rats 30 or 90 min before oral administration of ethanol. Mucosal damage and the glandular NP-SH levels were measured 1 h after ethanol. Both honey and sucralfate dose-dependently afforded protection against gastric damage and reversed the changes in glandular NP-SH levels induced by ethanol. Ranitidine was ineffective in this model. Pretreatment with indomethacin (IND) did not alter the protective effects of honey or the NP-SH levels, but significantly reduced the protective effects of sucralfate. On the other hand, pretreatment with N-ethylmaleimide (NEM) significantly reduced the protective effects of both honey and sucralfate and lowered the NP-SH levels. Combined IND and NEM treatment caused a significant reduction of the protective effects of honey and the NP-SH levels, but the values were not significantly different from those obtained with NEM alone. In contrast, combined IND plus NEM treatment completely abolished the protective effects of sucralfate and significantly lowered the NP-SH levels. Although these results suggest the involvement of prostaglandins (PGs) -- sensitive process in the protective effects of sucralfate, but honey and sucralfate (partially) share a common mechanisms of action in mediating the gastroprotective effects through NP-SH sensitive processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ca2+ transport and oxidative damage of mitochondria

1. Mitochondria from a wide range of sources have the ability to accumulate Ca2+ down their electrochemical gradient mediated by a uniport mechanism. 2. Ca2+ efflux occurs via two separate pathways: a Na+/Ca2+ exchanger that predominates in mitochondria from excitable tissues and a Na(+)-independent pathway that predominates in mitochondria from non-excitable tissues. 3. The kinetic characteristics of these calcium influx-efflux pathways appear to be incompatible with any role for mitochondria as cytosolic Ca2+ buffers, under resting normal physiological conditions. Instead, the biological role of this Ca(2+)-transporting system seems to be the regulation of matrix Ca2+ in a range that permits the regulation of three intramitochondrial Ca(2+)-dependent dehydrogenases which catalyze rate-limiting reactions of the Krebs cycle. 4. Under conditions in which a high cytosolic Ca2+ concentration is sustained, the matrix Ca2+ concentration may attain levels that lead to impairment of mitochondrial functions such as inhibition of oxidative phosphorylation and increase in inner membrane permeability. 5. Accumulation of Ca2+ by mitochondria under conditions of oxidative stress induces an increase in inner membrane permeability by a mechanism that appears to be mediated by protein polymerization due to thiol cross-linking

Influence of alpha-tocopherol on doxorubicin-induced lipid peroxidation, swelling and thiol depletion in rat heart mitochondria.

Effect of alpha-tocopherol on doxorubicin-induced swelling in rat heart mitochondria was studied in vitro. Mitochondria was isolated from control and alpha-tocopherol treated rats. Various concentrations of doxorubicin were added to mitochondrial suspension. Swelling, lipid peroxidation and thiol depletion were measured. Concentration and time dependent increase in swelling was noted with increase in lipid peroxidation and thiol depletion in mitochondria isolated from control rats. In alpha-tocopherol treatment, thiol depletion is significantly prevented with reduced lipid peroxidation and swelling.

Effect of methylglyoxal on protein thiol and amino groups in isolated rat enterocytes and colonocytes and activity of various brush border enzymes.

The effect of methylglyoxal on protein -SH and -NH2 groups in cytosolic and membranous fractions of epithelial cells lining the gastrointestinal tract of rat was investigated, using isolated villus and crypt cells (enterocytes) and colonocytes. It was found that 11-12% cytosolic protein -SH and 14-17% membrane protein -SH groups were lost when villus and crypt cells were treated with 2 mM methylglyoxal. In colonocytes, the corresponding loss in protein -SH groups was 46 and 30% under the same treatment. Similarly, 27-37% protein -NH2 group in the cytosolic fraction and 18-19% protein -NH2 group in membranous fractions of the enterocytes were lost by 2 mM methylglyoxal treatment. In colonocytes, the loss of protein -NH2 group was 30 and 15% in cytosolic and membranous fractions, respectively, under the same treatment. Effect of methylglyoxal on activity of various brush border enzymes such as alkaline phosphatase, gamma-glutamyl transpeptidase, leucine aminopeptidase, Mg2(+)-ATPase, sucrase and lactase was also studied. Alkaline phosphatase and gamma-glutamyl transpeptidase activities were inhibited to the extent of 30 and 15% respectively. There was no significant change in the activities of other enzymes after treating the brush border vesicles with 2 mM methylglyoxal. These findings show that methylglyoxal can cause loss of protein thiol and amino groups and enzyme activity in mucosal cells of rat gastrointestinal tract and the effect is more pronounced in colonocytes, which are in constant contact with bacterial metabolites.