Effect of trans-resveratrol on glutamate clearance and visual behaviour in rats with glutamate induced retinal injury.

Glutamate-induced excitotoxic injury is widely described as a prominent pathophysiological mechanism in several neurodegenerative diseases including glaucoma. Glaucoma, the leading cause of irreversible blindness, is characterized by loss of retinal ganglion cells (RGC). Currently, the treatment focuses on lowering intraocular pressure (IOP) and no neuroprotective therapies are available. Since excessive glutamate-mediated neurotransmission underlies glaucomatous RGC apoptosis, enhancing synaptic glutamate clearance by glutamate transporters in glial cells is expected to protect against excitotoxic injury. Trans-resveratrol is known for its neuroprotective effects; however, its effects on the expression of glutamate transporters and glutamate clearance in retina remain unclear. Hence, in the current study, we investigated the protective effects of trans-resveratrol against glutamate-induced retinal injury in rats. Rats were intravitreally injected with glutamate alone or glutamate with trans-resveratrol as pre- and post-treatment. Animals were subjected to Open Field Test (OFT) on day six and a two-chamber mirror test on day seven post-injection. Subsequently, rats were sacrificed and retinal expression of excitatory amino acid transporter (EAAT)1 and EAAT2 gene and protein was determined using PCR and ELISA, respectively. Retinal glutamate concentration was measured using ELISA and retinal morphology was studied on H&E-stained retinal sections. It was observed that pre-treatment with trans-resveratrol causes gene expression for EAAT1 and EAAT2 to increase by 2.51 and 1.93 folds compared to glutamate-treated group (p < 0.001 and p < 0.01, respectively); while the same in trans-resveratrol post-treatment group showed a 1.58- and 1.44 folds upregulation (p < 0.05).The retinal EAAT1 and EAAT2 protein expression was significantly greater in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.05) but not in post-treatment group. Retinal glutamate concentration was1.64 folds greater in glutamate-treated group than the vehicle-treated group (p < 0.01) but the same was 1.27-fold lower in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.01). Corresponding to these findings, we observed preservation of retinal morphology and visual behaviour in trans-resveratrol pre-treatment group compared to glutamate-treated group. We did not observe similar effects of trans-resveratrol when it was given as post-treatment after glutamate administration. In conclusion, current study showed that pre-treatment with trans-resveratrol protects against glutamate induced changes in retinal morphology and visual behaviour by increasing the expression of EAAT1 and EAAT2 and increasing glutamate clearance in rat retinas. The results of this study may be relevant to disease conditions involving excitotoxic neuronal injury.

Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease-A randomized controlled trial.

INTRODUCTION: There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD). MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages. RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events. CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.

Methanolic Extract of Piper sarmentosum Attenuates Obesity and Hyperlipidemia in Fructose-Induced Metabolic Syndrome Rats.

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG-Untreated group; CTRL-control; FDW-olive oil + 20% fructose; FDW-PS-PS (125 mg/kg) + 20% fructose; FDW-NGN-naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia.

Neuroprotective effects of brain-derived neurotrophic factor against amyloid beta 1-40-induced retinal and optic nerve damage.

Brain-derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aß)-associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aß1-40-induced retinal and optic nerve injury. In this study, exposure to Aß1-40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF-treated group compared with Aß1-40 group. H&E-stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aß1-40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF-treated animals. After Aß1-40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF-treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aß was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF-treated than in Aß1-40-treated rats. Both visual object recognition tests using an open-field arena and a Morris water maze showed that BDNF improved rats' ability to recognise visual cues (objects with different shapes) after Aß1-40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aß1-40-induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.

Data on the effects of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds on intraocular pressure of ocular normotensive rats.

This data is to document the intraocular pressure (IOP) lowering activity of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds in ocular normotensive rats. Effects of single drop application of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds on IOP in ocular normotensive rats are presented at 3 different concentrations (0.1%, 0.2% and 0.4%). Time course of changes in IOP is presented over 6 h period post-instillation. The IOP lowering activities of test compounds were determined by assessing maximum decrease in IOP from baseline and corresponding control, duration of IOP lowering and area under curve (AUC) of time versus response curve. Data shown here may serve as benchmarks for other researchers studying IOP-lowering effect of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds and would be useful in determining therapeutic potential of these test compounds as IOP lowering agents.

Effect of Magnesium Acetyltaurate and Taurine on Endothelin1-Induced Retinal Nitrosative Stress in Rats.

PURPOSE: Retinal ganglion cell apoptosis in glaucoma is associated with elevated levels of endothelin-1 (ET1), a potent vasoconstrictor. ET1-induced retinal ischemia leads to altered expression of nitric oxide synthase (NOS) isoforms leading to increased formation of nitric oxide (NO) and retinal nitrosative stress. Since magnesium (Mg) is known to improve endothelial functions and reduce oxidative stress and taurine (TAU) possesses potent antioxidant properties, we investigated the protective effects of magnesium acetyltaurate (MgAT) against ET1-induced nitrosative stress and retinal damage in rats. We also compared the effects of MgAT with that of TAU alone. METHODS: Sprague Dawley rats were intravitreally injected with ET1. MgAT and TAU were administered as pre-, co-, or posttreatment. Subsequently, the expression of NOS isoforms was detected in retina by immunohistochemistry, retinal nitrotyrosine level was estimated using ELISA, and retinal cell apoptosis was detected by TUNEL staining. RESULTS: Intravitreal ET1 caused a significant increase in the expressions of nNOS and iNOS while eNOS expression was significantly reduced compared to vehicle treated group. Administration of both MgAT and TAU restored the altered levels of NOS isoform expression, reduced retinal nitrosative stress and retinal cell apoptosis. The effect of MgAT, however, was greater than that of TAU alone. CONCLUSIONS: MgAT and TAU prevent ET1-induced retinal cell apoptosis by reducing retinal nitrosative stress in Sprague Dawley rats. Addition of TAU to Mg seems to enhance the efficacy of TAU compared to when given alone. Moreover, the pretreatment with MgAT/TAU showed higher efficacy compared to co- or posttreatment.

Time- and dose-related effects of amyloid beta1-40 on retina and optic nerve morphology in rats.

PURPOSE: Amyloid beta (Aß) is known to contribute to the pathophysiology of retinal neurodegenerative diseases such as glaucoma. Effects of intravitreal Aß(1-42) on retinal and optic nerve morphology in animal models have widely been studied but not those of Aß(1-40). Hence, we evaluated the time- and dose-related effects of intravitreal Aß(1-40) on retinal and optic nerve morphology. Since oxidative stress and brain derived neurotrophic factor (BDNF) are associated with Aß-induced neuronal damage, we also studied dose and time-related effects of Aß(1-40) on retinal oxidative stress and BDNF levels. MATERIALS AND METHODS: Five groups of rats were intravitreally administered with vehicle or Aß(1-40) in doses of 1.0, 2.5, 5 and 10 nmol. Animals were sacrificed and eyes were enucleated at weeks 1, 2 and 4 post-injection. The retinae were subjected to morphometric analysis and TUNEL staining. Optic nerve sections were stained with toluidine blue and were graded for neurodegenerative effects. The estimation of BDNF and markers of oxidative stress in retina were done using ELISA technique. RESULTS AND CONCLUSIONS: It was observed that intravitreal Aß(1-40) causes significant retinal and optic nerve damage up to day 14 post-injection and there was increasing damage with increase in dose. However, on day 30 post-injection both the retinal and optic nerve morphology showed a trend towards normalization. The observations made for retinal cell apoptosis, retinal glutathione, superoxide dismutase activity and BDNF were in accordance with those of morphological changes with deterioration till day 14 and recovery by day 30 post-injection. The findings of this study may provide a guide for selection of appropriate experimental conditions for future studies.

Intraocular pressure lowering effect and structure-activity relationship of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds in ocular normotensive rats: Insight on possible link with hypotensive activity.

In an effort to find new ocular hypotensive drug candidates, a total of 27 condensed benzimidazoles based compounds were screened. This study was done in normotensive rats and rebound tonometry was used to estimate IOP. All compounds were topically applied as a single drop, unilaterally, at 3 different concentrations (0.1%, 0.2% and 0.4%). The contralateral eye was instilled with vehicle and served as control. The IOP reduction was measured up to 6h. It was observed that with a single topical instillation, compounds RU 551, RU 555, RU839 (pyrimido[1,2-a]benzimidazole derivatives), and RU 615 (imidazo[1,2-a]benzimidazole derivative) showed significant IOP lowering activities in ocular normotensive rats. All other compounds showed none, weak and inconsistent IOP lowering effect. The relationship between ability of IOP lowering and hypotensive activities was studied. According to the pharmacophore analysis, the class of pyrimido[1,2-a]benzimidazole is more promising than the class of imidazo[1,2-a]benzimidazole as a source of compounds with high IOP lowering activity. Pharmacophore analysis also showed that the critical features of high IOP lowering activity are methoxyphenyl and [phenyl]alkyl fragments, and non-conjugated six-membered heterocyclic ring.

Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats.

Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels.

Intraocular distribution of topically applied hydrophilic and lipophilic substances in rat eyes.

PURPOSE: Topical administration is the preferred route of drug delivery for ophthalmic ailments. However, poor permeation through ocular surface and significant systemic absorption, makes the topical drug delivery challenging. Furthermore, distribution of topically delivered drugs varies with their physicochemical properties and the type of formulation used. Hence, this study was done to understand the pattern of ocular drug distribution of topically applied hydrophilic and lipophilic substances in two different formulations. METHODS: 5-Carboxyfluorescein and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate were used as representative candidates for hydrophilic and lipophilic substances, respectively. They were formulated in solution and liposomes. Single drop of either formulation containing hydrophilic or lipophilic substance was instilled topically, unilaterally to rat eyes. Subsequently, rats were sacrificed at 10, 30 and 120 min post-instillation. Eyes were cryosectioned and examined under confocal microscope to determine the fluorescence intensity in ocular tissues. RESULTS: Corneal permeation of hydrophilic and lipophilic substances in both formulations peaked at 30 min post-instillation. Liposomal-lipophilic dye and non-liposomal-hydrophilic dye showed better corneal distribution. Fluorescence was absent in contralateral eyes of non-liposomal-hydrophilic dye-treated animals but was present in contralateral eyes of liposomal-hydrophilic dye-treated animals. Fluorescence in contralateral eyes of liposomal-lipophilic dye-treated animals was significantly higher compared to non-liposomal-lipophilic dye-treated animals. CONCLUSIONS: Topically applied liposomal formulation of lipophilic substance provides higher corneal concentration of drug with lesser systemic absorption compared to its solution. For hydrophilic substance, topical use of solution provides greater corneal concentration compared to liposomes which is more likely to be absorbed systemically.

Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in normotensive rats.

Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have similarity with those of prostaglandin analogs. The present study investigated the involvement of matrix metalloproteinases (MMPs) and cytokine activity modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor. Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering effect of ACEI. Topical treatment with single drop of enalaprilat resulted in significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h post-instillation. Treatment with losartan resulted in a peak IOP reduction of 13.3%, which was significantly lower than enalaprilat, indicating involvement of mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin II type 1 receptor stimulation and modulation of MMP and cytokines activities.

Knowledge, practices and attitudes towards adverse drug reaction reporting by private practitioners from klang valley in malaysia.

BACKGROUND: The study aimed to determine current status of knowledge, practices, and attitudes towards adverse drug reaction (ADR) reporting among private practitioners in Klang region of Malaysia. METHODS: A total of 238 private practitioners in Klang valley were distributed a questionnaire consisting of seven questions, two knowledge-related, two practice-related and three attitude-related. Each favourable and unfavourable response was given a score of 1 and 0 respectively. Total score of 70% or more for each domain was considered "satisfactory" whereas less than 70% as "unsatisfactory". RESULTS: One hundred forty-five participants completed questionnaire. Knowledge assessment showed 83.4% responses stating that ADR reporting helps to identify safe drugs and 91.7% responded that it measures ADR incidence. Regarding practices, 76.6% respondents were willing to report only if confident that reaction is an ADR. Regarding attitudes, 81.9%, 66.9% and 23.5% participants showed complacency, ignorance, and indifference respectively. Unsatisfactory knowledge, practices, and attitudes were observed in 57.2%, 56.6%, and 73.1% respondents respectively. Satisfactory knowledge was significantly higher in respondent with higher qualification with odds ratio of 2.96 with 95% confidence interval of 1.48-5.93. CONCLUSION: The study showed unsatisfactory level of knowledge, practices, and attitudes towards ADR reporting among high proportion of private practitioners in Klang valley, Malaysia.

Effects of magnesium taurate on the onset and progression of galactose-induced experimental cataract: in vivo and in vitro evaluation.

Cataract, a leading cause of blindness, is characterized by lenticular opacities resulting from denaturation of lens proteins due to activation of calcium-dependent enzyme, calpain. Magnesium (Mg(2+)) plays an important role not only in maintaining a low lenticular calcium (Ca(2+)) and sodium concentration but also in preserving the lens redox status. Taurine has also been shown to reduce lenticular oxidative stress. Present study evaluated the anticataract effects of magnesium taurate in vivo and in vitro. Among the five groups of 9 Sprague Dawley rats each, two groups received 30% galactose diet with topical (GDMT) or oral treatment (GDMO) with magnesium taurate. Two groups received 30% galactose diet with topical (GDT) or oral vehicle (GDO). Remaining 1 group received normal diet (ND). Weekly slit lamp examination was done during 21 days experimental period and then all rats were sacrificed; Ca/Mg ratio and antioxidant parameters including reduced glutathione (GSH), catalase and superoxide dismutase (SOD) activities were measured in the isolated lenses using ELISA. In the in vitro study, 2 groups of 10 normal rat lenses were incubated in Dulbecco's Modified Eagle's Medium (DMEM) with galactose while 1 similar group was incubated in DMEM without galactose. In one of the groups, galactose containing medium was supplemented with magnesium taurate. After 48 h of incubation, lenses were photographed and Ca(2+)/Mg(2+) ratio and antioxidant parameters were measured as for in vivo study. The in vivo study, at the end of experimental period, demonstrated delay in the development of cataract with a mean opacity index of 0.53 ± 0.04 and 0.51 ± 0.03 in GDMO (p < 0.05 versus GDO) and GDMT (p < 0.01 versus GDT) respectively. Histopathological grading showed a lower mean value in treated groups, however, the differences from corresponding controls were not significant. Lenticular Ca(2+)/Mg(2+) ratio with a mean value of 1.20 ± 0.26 and 1.05 ± 0.26 in GDMO and GDMT was significantly lower than corresponding controls (p < 0.05) and in GDMT no significant difference was observed from ND. Lenticular GSH and catalase activities were significantly lower and SOD activity was significantly higher in all galactose fed groups. However, in GDMT, GSH and catalase were significantly higher than corresponding control with mean values of 0.96 ± 0.30 µmol/gm lens weight and 56.98 ± 9.86 µmol/g lens protein respectively (p < 0.05 for GSH and p < 0.01 for catalase). SOD activity with mean values of 13.05 ± 6.35 and 13.27 ± 7.61 units/mg lens protein in GDMO and GDMT respectively was significantly lower compared to corresponding controls (p < 0.05) signifying lesser upregulation of SOD due to lesser oxidative stress in treated groups. In the in vitro study, lenses incubated in magnesium taurate containing medium showed less opacity and a lower mean Ca(2+)/Mg(2+) ratio of 1.64 ± 0.03, which was not significantly different from lenses incubated in DMEM without galactose. Lens GSH and catalase activities were restored to normal in lenses incubated in magnesium taurate containing medium. Both in vivo and in vitro studies demonstrated that treatment with magnesium taurate delays the onset and progression of cataract in galactose fed rats by restoring the lens Ca(2+)/Mg(2+) ratio and lens redox status.

Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress.

BACKGROUND: This study examined the effects of Palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO + XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). METHODS: Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO + XD activities. RESULTS: The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and α-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and α-TF treatments reduced these parameters significantly compared to the stressed control. CONCLUSIONS: Supplementations with either PVE or α-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.