In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease

@# Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

Monoterpenes: Novel insights into their biological effects and roles on glucose uptake and lipid metabolism in 3T3-L1 adipocytes.

Various strategies have been adopted to combat complications caused by Type 2 diabetes mellitus and controlled diet is one of them. Monoterpenes, major constituents of essential oils, are synthesized and widely used as artificial food flavors. A series of twelve monoterpenes were assessed in the present study. Monoterpenes, exhibited low 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity even at high concentrations. Some monoterpenes inhibited α-amylase and α-glucosidase activity and stimulated glucose uptake and lipolysis. Monoterpenes such as (R)-(+)-limonene stimulated both glucose uptake (17.4%) and lipolysis (17.7%); the mRNA expression of glucose transporter 1 (GLUT1) was upregulated but glucose transporter 4 (GLUT4) was unaffected, and adipose triglyceride lipase (ATGL) was suppressed. Taken together, the selected monoterpenes may not confer strong protection against free radicals but nevertheless, their positive influence on lipid and glucose metabolism may have potential in the control of obesity and Type 2 diabetes mellitus.

AMP-activated protein kinase mediates insulin-like and lipo-mobilising effects of ß-glucan-rich polysaccharides isolated from Pleurotus sajor-caju (Fr.), Singer mushroom, in 3T3-L1 cells.

Mushrooms have been used to treat various diseases for thousands of years. In the present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis, lipolysis and oxidative stress in 3T3-L1 cells were investigated. The ß-glucan-rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells. This extract caused an increase in the expression of 5'-AMP-activated protein kinase subunit γ-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit γ-3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes, leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have contributed to the lipolytic and insulin-like activities observed in this study. These findings suggest that GE is a novel AMPK activator that may be valuable in the formulation of nutraceuticals and functional food for the prevention and treatment of diabetes mellitus.

Beta-Glucan-Rich Extract from Pleurotus sajor-caju (Fr.) Singer Prevents Obesity and Oxidative Stress in C57BL/6J Mice Fed on a High-Fat Diet.

Mushrooms have been used in folk medicine for thousands of years. In this study, the effect of ß -glucan-rich extract of P. sajor-caju (GE) on lipid lowering and antioxidant potential was assessed in C57BL/6J mice fed on a high-fat diet. Obesity was induced in C57BL/6J mice by feeding a high-fat diet. The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120, and HFD240 (for high-fat diet), where the mice were administrated with three dosages of GE (60, 120, and 240 mg GE/kg b.w). Metformin (2 mg/kg b.w) served as positive control. GE-treated groups showed significantly reduced body weight, serum lipid, and liver enzymes levels. GE also attenuated protein carbonyl and lipid hydroperoxide levels by increasing the enzymic antioxidants (SOD, CAT, and GPx) activities in the mice. GE-treated groups induced the expression of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) while downregulated the expression of peroxisome proliferator-activated receptor gamma (PPAR- γ ), sterol regulatory binding protein-1c (SREBP-1c), and lipoprotein lipase (LPL). Hence, GE prevented weight gain in the mice by inducing lipolysis and may be valuable in the formulation of adjuvant therapy for obesity.

Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients.

Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in beta-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.

Chemical composition and antioxidant properties of extracts of fresh fruiting bodies of Pleurotus sajor-caju (Fr.) Singer.

The chemical composition and in vitro antioxidant activity of aqueous butanol and ethyl acetate extracts of Pleurotus sajor-caju were investigated in this study. Twenty-two compounds comprising methyl esters, hydrocarbon fatty acids, ethyl esters, and sterols were identified in ethyl acetate extracts, while cinnamic acid, nicotinamide, benzeneacetamide, and 4-hydroxybenzaldyhde were identified in butanol extracts by gas chromatography-mass spectrometry and NMR analysis. The antioxidant activity was determined by a ß-carotene bleaching method, ferric reducing antioxidant power, trolox equivalent antioxidant capacity, and lipid peroxidation assays, while the total phenolic content in P. sajor-caju was assessed by Folin-Ciocalteau's method. The aqueous and butanol extracts exhibited the highest antioxidant activity, corresponding to the total phenolic content. The subfractions from the ethyl acetate extract (EP1, EP2, EP3, and EP4), however, showed moderate antioxidant activity. The regular consumption of P. sajor-caju as a part of our diet may render nutritional and nutraceuticals benefits for good health.

Urinary hyaluronidase activity in rats infected with Blastocystis hominis--evidence for invasion?

The fact whether Blastocystis hominis can invade has always been in question. Apart from a few sporadic studies such as that done on gnotobiotic guinea pigs which showed surface invasion and mucosal inflammation of the host's intestine caused by B. hominis infection, no real documentation of invasion has been proven. Studies have shown that hyaluronidase is secreted during the penetration into the host's skin and gut by nematode parasites. Hyaluronidase activity in protozoa namely Entamoeba histolytica has also been described previously. This study attempts to determine hyaluronidase in urine samples of B. hominis-infected rats. The presence of hyaluronidase in urine provides an indirect evidence of invasion by B. hominis into colonic epithelium causing the degradation of extracellular matrix proteins namely hyaluronic acid (HA). HA is depolymerized by hyaluronidase which may be used by organisms to invade one another. In this study, the levels of urinary hyaluronidase of Sprague-Dawley rats infected with B. hominis were monitored for 30 days. Hyaluronidase levels in the infected rats were significantly higher on days 28 and 30 compared to the day before inoculation (P < 0.01 and P < 0.05, respectively). During this stage, parasitic burden in infected stools was also at a high level. Proinflammatory cytokines, interleukin-6 and interleukin-8, were also significantly higher (P < 0.05) in the serum of infected rats. The study demonstrates that since no other pathogen was present and that amoeboid forms of the parasites have been shown to exist previously, the elevated levels of hyaluronidase in this preliminary finding suggests that the organism is capable of having invasion or penetration activity in the hosts' intestine.

High levels of oxidative stress in rats infected with Blastocystis hominis.

OBJECTIVE: Numerous studies have revealed the presence of oxidative stress in parasitic infections. However, such studies were lacking in the Malaysian population. Previously, we have provided evidence that oxidative stress is elevated in Malaysians infected with intestinal parasites. Stool examinations revealed that about 47.5% of them were infected with the polymorphic protozoa, Blastocystis hominis. However, they were found to have mixed infection with other intestinal parasites. METHODOLOGY: Therefore, in order to investigate the role of B. hominis alone in affecting oxidative stress status, here we compared the levels of oxidative stress biomarkers in urine and blood samples between uninfected and B. hominis-infected rats. RESULTS: Infected rats exhibited elevated levels of oxidative indices namely advanced oxidative protein products (AOPP), hydrogen peroxide (H2O2) and lipid hydroperoxide (LHP) indicating that their overall oxidative damage level was higher. Ferric reducing antioxidant power (FRAP) was elevated at the initial stage of infection but decreased significantly during the last week of study duration suggesting that the antioxidant status of the host may be overwhelmed by oxidative damage. CONCLUSION: To date, this is the first comprehensive in vivo study to provide evidence for Blastocystis infection to correlate with significant oxidative burst leading to oxidative stress.

Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.

Lentinula edodes (Berk) Pegler, commonly known as Shiitake mushroom has been used as medicinal food in Asian countries, especially in China and Japan and is believed to possess strong immunomodulatory property. In the present study, the methanolic extract of the fruit bodies of L. edodes was investigated for cytoprotective effect against H2O2-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) by measuring the activities of xanthine oxidase (XO) and glutathione peroxidase (GPx) . H2O2 at a concentration of 5 microM caused 50% inhibition of PBMCs viability. The extract improved the PBMC viability and exerted a dose-dependent protection against H2O2-induced cytotoxicity. At 100 microg/ml of extract concentration, the cell viability increased by 60% compared with the PBMCs incubated with H2O2 alone. The extract also inhibited XO activity in PBMC, while showing moderate stimulatory effect on GPx. However, in the presence of H2O2 alone, both the enzyme activities were increased significantly. The GPx activity increased, possibly in response to the increased availability of H2O2 in the cell. When the cells were pretreated with the extract and washed (to remove the extract) prior to the addition of H2O2, the GPx and XO activities as well as the cell viability were comparable to those when incubated with the extract alone. Thus, it is suggested that one of the possible mechanisms via which L. edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC is by inhibiting the superoxide-producing XO and increasing GPx activity which could rapidly inactivate H2O2.

Antioxidant capacity of fresh and processed fruit bodies and mycelium of Auricularia auricula-judae (Fr.) Quél.

Auricularia auricula-judae is currently grown in Malaysia. In the present study, the methanolic extracts from fruit bodies (fresh, oven-dried, and freeze-dried) and mycelium of A. auricula-judae were evaluated for their antioxidant capacities based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and ferric reducing antioxidant power (FRAP) assay. The total phenolic content in the extracts were also measured. The extract of freeze-dried fruit bodies of A. auricula-judae had potent DPPH free radical scavenging activity with a 50% effective concentration of 2.87 mg/mL, whereas the FRAP value of A. auricula-judae mycelium was 5.22 micromol of FeSO(4).7H(2)O equivalents/g of mycelium sample. Further, a positive correlation (R(2) = 0.7668) between FRAP level of A. auricula-judae extracts and the total phenolic contents was observed. Thus the method of processing of fresh fruit bodies had an effect on the antioxidant potential of A. auricula-judae.

Elevated levels of urinary hydrogen peroxide, advanced oxidative protein product (AOPP) and malondialdehyde in humans infected with intestinal parasites.

Oxidative stress has been implicated as an important pathogenic factor in the pathophysiology of various life-threatening diseases such as cancer, cardiovascular diseases and diabetes. It occurs when the production of free radicals (generated during aerobic metabolism, inflammation, and infections) overcome the antioxidant defences in the body. Although previous studies have implied that oxidative stress is present in serum of patients with parasitic infection there have been no studies confirming oxidative stress levels in the Malaysian population infected with intestinal parasites. Three biochemical assays namely hydrogen peroxide (H2O2), lipid peroxidation (LP) and advanced oxidative protein product (AOPP) assays were carried out to measure oxidative stress levels in the urine of human subjects whose stools were infected with parasites such as Blastocystis hominis, Ascaris, Trichuris, hookworm and microsporidia. The levels of H2O2, AOPP and LP were significantly higher (P<0.001, P<0.05 and P<0.05 respectively) in the parasite-infected subjects (n=75) compared to the controls (n=95). In conclusion, the study provides evidence that oxidative stress is elevated in humans infected by intestinal parasites. This study may influence future researchers to consider free radical-related pathways to be a target in the interventions of new drugs against parasitic infection and related diseases.

Comparative assessment of urinary oxidative indices in breast and colorectal cancer patients.

PURPOSE: This study aimed to use non-invasive methods to assess and compare the levels of oxidative indices and non-enzymatic antioxidants in breast and colorectal cancer (CRC) patients. Various studies have reported on lipid peroxidation, hydrogen peroxide (H(2)O(2)) and ferric-reducing antioxidant power (FRAP) levels in the serum of cancer patients but this is the first report that highlights the significance of urinary-advanced oxidative protein product (AOPP) in cancer patients. METHODS: The levels of advanced oxidative protein product (AOPP), hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA) which is a marker for lipid peroxidation and ferric-reducing antioxidant power (FRAP) were measured in urine samples of breast (n = 101) and colorectal cancer (n = 49) patients attending the Oncology Clinic, University Malaya Medical Centre, Kuala Lumpur and were compared with 95 age-matched healthy individuals. RESULTS: AOPP, H(2)O(2) and MDA levels in the urine were significantly higher in the CRC patients compared to the control subjects and breast cancer patients. In breast cancer patients, only AOPP level was elevated. FRAP level did not differ between breast and colorectal cancer patients but the levels were significantly lower compared to control subjects. CONCLUSION: Urinary oxidative indices such as AOPP, H(2)O(2), and MDA as well as FRAP could serve as useful non-invasive oxidative stress markers in colorectal cancer but only AOPP serves as a useful urinary oxidative biomarker in breast cancer.

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats.

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients.

The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.

Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patients.

AIMS: Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant-antioxidant levels in these patients. METHODS: Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods. RESULTS: Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA(1c), fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant-antioxidant parameters as a function of HbA(1c) in each ethnic group revealed a strong association of HbA(1c) with oxidative indices. CONCLUSIONS: The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA(1c) remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration.

Antioxidant enzyme activities of human peripheral blood mononuclear cells exposed to trace elements.

The trace elements copper, zinc, and selenium are important immune modulators and essential cofactors of the antioxidant enzymes. In the present study, the proliferative effect of human peripheral mononuclear cells (PBMCs) that have been exposed to copper, zinc, and selenium and the corresponding activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, were determined. Zinc and copper stimulated the PBMC proliferation in a dose-dependent manner within the dose range 25-200 micromol/L. SOD and GPx activities in PBMCs exposed to zinc were inhibited, whereas catalase activity was unaffected. All the three antioxidant enzymes in the cells exposed to copper were inhibited. Selenium exerted more potent inhibition of the cell proliferation while causing stimulation of the antioxidant enzymes at the lowest dose (25 micromol/L) than at the highest dose (200 micromol/L) tested. A significant negative correlation was observed between proliferation and antioxidant enzyme (SOD and GPx) activities in trace-element-exposed PBMC. The present findings substantiate the importance of trace elements as immune modulators and the involvement of enzymatic antioxidant system in the immune cell regulation.

Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus.

BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population. METHOD: The assays were carried out according to known established protocols. RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels. CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.