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Preventive Medicine 02/2012; 54 Suppl:S12-6. · 3.22 Impact Factor
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Jhoti Somanah, Okezie I Aruoma,
Teeluck K Gunness,
Sudhir Kowelssur,
Venkatesh Dambala,
Fatima Murad,
Kreshna Googoolye,
Diana Daus,
Joseph Indelicato,
Emmanuel Bourdon,
Theeshan Bahorun
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ABSTRACT: Clinical evidence and cellular models have shown an inverse relationship between the intakes of plant and fruit based diets and oxidative stress, suggesting the suitability of natural antioxidants in the management of diabetes mellitus and its complications.
A randomized controlled clinical trial was conducted at the Cardiac Centre, SSRN Hospital, Pamplemousses, (Mauritius) to determine the effect of a short term supplementation of a fermented papaya preparation (FPP®) on biomarkers of diabetes and antioxidant status in a multi-ethnical neo-diabetic population from November 2010 to March 2011.
Supplementation of 6g FPP®/day for a period of 14 weeks could improve the general health status of several organs targeted by oxidative stress during diabetes. When comparing experimental to control groups with independent samples t-test, C-reactive protein levels significantly decreased (P=0.018), LDL/HDL ratio was considerably changed (P=0.042), and uric acid levels were significantly improved (P=0.001). ANOVA results also validated the same findings with significant differences in C-reactive protein, LDL/HDL ratio, uric acid and in serum ferritin levels.
FPP® may present a novel, economically feasible nutraceutical supplement for the management of diabetes and for those at risk for cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress.
Preventive Medicine 02/2012; 54 Suppl:S90-7. · 3.22 Impact Factor
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ABSTRACT: A prospective randomized controlled clinical trial determined the effect of Mauritian black tea consumption on fasting blood plasma levels of glucose, lipid profiles and antioxidant status in a normal population.
The study group (71%) consumed 3 x 200 ml of black tea infusate/day for 12 weeks without additives followed by a 3 week wash-out. The control group (29%) consumed equivalent volume of hot water for same intervention period.
The tea used had high levels of gallic acid derivatives (50 ± 0.4 mg/L), flavan-3-ols (42 ± 2 mg/L), flavonols (32 ± 1 mg/L) and theaflavins (90 ± 1 mg/L). Daily 9 g supplementation of black tea infusate induced, in a normal population, a highly significant decrease of fasting serum glucose (18.4%; p<0.001) and triglyceride levels (35.8%; p<0.01), a significant decrease in LDL/HDL plasma cholesterol ratio (16.6%; p<0.05) and a non significant increase in HDL plasma cholesterol levels (20.3%), while a highly significant rise in plasma antioxidant propensity (FRAP: 418%; p<0.001) was noted .
Black tea consumed within a normal diet contributes to a decrease of independent cardiovascular risk factors and improves the overall antioxidant status in humans.
Preventive Medicine 12/2011; 54 Suppl:S98-102. · 3.22 Impact Factor
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ABSTRACT: Fermented papaya preparation (FPP) (a product of yeast fermentation of Carica papaya Linn) is a food supplement. Studies in chronic and degenerative disease conditions (such as thalassemia, cirrhosis, diabetes and aging) and performance sports show that FPP favorably modulates immunological, hematological, inflammatory, vascular and oxidative stress damage parameters. Neuroprotective potential evaluated in an Alzheimer's disease cell model showed that the toxicity of the β-amyloid can be significantly modulated by FPP. Oxidative stress trigger apoptotic pathways such as the c-jun N-terminal kinase (JNK) and p38-mitogen activated protein kinase (MAPK) are preferentially activated by pro-inflammatory cytokines and oxidative stress resulting in cell differentiation and apoptosis. FPP modulated the H₂O₂-induced ERK, Akt and p38 activation with the reduction of p38 phosphorylation induced by H₂O₂. FPP reduces the extent of the H₂O₂-induced DNA damage, an outcome corroborated by similar effects obtained in the benzo[a]pyrene treated cells. No genotoxic effect was observed in experiments with FPP exposed to HepG2 cells nor was FPP toxic to the PC12 cells. Oxidative stress-induced cell damage and inflammation are implicated in a variety of cancers, diabetes, arthritis, cardiovascular dysfunctions, neurodegenerative disorders (such as stroke, Alzheimer's disease, and Parkinson's disease), exercise physiology (including performance sports) and aging. These conditions could potentially benefit from functional nutraceutical/food supplements (as illustrated here with fermented papaya preparation) exhibiting anti-inflammatory, antioxidant, immunostimulatory (at the level of the mucus membrane) and induction of antioxidant enzymes.
Toxicology 11/2010; 278(1):6-16. · 3.68 Impact Factor
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ABSTRACT: The flavedo extracts of twenty-one varieties of citrus fruits (oranges, satsumah, clementine, mandarins, tangor, bergamot, lemon, tangelos, kumquat, calamondin and pamplemousses) grown in Mauritius were examined for their total phenolic, flavonoid and vitamin C contents and antioxidant activities. Total phenolics correlated strongly with the trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant capacity (FRAP) and hypochlorous acid (HOCl) scavenging activity assays (r > 0.85). Based on their antioxidant activities in these three assays nine citrus fruits namely, one orange, clementine, tangor and pamplemousse variety, two tangelo varieties and three mandarin varieties, were further characterized for their flavanone, flavonol and flavone levels by HPLC and their antioxidant activities were assessed by the copper-phenanthroline and iron chelation assays. The flavanone, hesperidin, was present at the highest concentrations in all flavedo extracts except for pamplemousses where it was not detected. Contents in hesperidin ranged from 83 ± 0.06 to 234 ± 1.73 mg/g FW. Poncirin, didymin, diosmin, isorhoifolin and narirutin were also present in all extracts whereas naringin was present only in one mandarin variety. The nine flavedo extracts exhibited good DNA protecting ability in the cuphen assay with IC₅₀ values ranging from 6.3 ± 0.46 to 23.0 ± 0.48 mg FW/mL. Essentially the flavedos were able to chelate metal ions however, tangor was most effective with an IC₅₀ value of 9.1 ± 0.08 mg FW/mL. The flavedo extracts of citrus fruits represent a significant source of phenolic antioxidants with potential prophylactic properties for the development of functional foods.
Toxicology 11/2010; 278(1):75-87. · 3.68 Impact Factor
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Okezie I Aruoma
Toxicology 09/2010; 278(1):2-5. · 3.68 Impact Factor
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Toxicology 09/2010; 278(2):161-4. · 3.68 Impact Factor
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ABSTRACT: Natural phytochemicals derived from dietary sources or medicinal plants have gained significant recognition in the potential management of several human clinical conditions. Much research has also been geared towards the evaluation of plant extracts as effective prophylactic agents since they can act on specific and/or multiple molecular and cellular targets. Plants have been an abundant source of highly effective phytochemicals which offer great potential in the fight against cancer by inhibiting the process of carcinogenesis through the upregulation of cytoprotective genes that encode for carcinogen detoxifying enzymes and antioxidant enzymes. The mechanistic insight into chemoprevention further includes induction of cell cycle arrest and apoptosis or inhibition of signal transduction pathways mainly the mitogen-activated protein kinases (MAPK), protein kinases C (PKC), phosphoinositide 3-kinase (PI3K), glycogen synthase kinase (GSK) which lead to abnormal cyclooxygenase-2 (COX-2), activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB) and c-myc expression. Effectiveness of chemopreventive agents reflects their ability to counteract certain upstream signals that leads to genotoxic damage, redox imbalances and other forms of cellular stress. Targeting malfunctioning molecules along the disrupted signal transduction pathway in cancer represent a rational strategy in chemoprevention. NF-κB and AP-1 provide mechanistic links between inflammation and cancer, and moreover regulate tumor angiogenesis and invasiveness, indicating that signaling pathways that mediate their activation provide attractive targets for new chemotherapeutic approaches. Thus cell signaling cascades and their interacting factors have become important targets of chemoprevention and phenolic phytochemicals and plant extracts seem to be promising in this endeavor.
Toxicology 10/2009; 278(2):229-41. · 3.68 Impact Factor
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ABSTRACT: Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX).
Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old).
Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes.
Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.
Cancer epidemiology. 09/2009; 33(3-4):293-9.
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ABSTRACT: Toxicology j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / t o x i c o l Keywords: Functional foods Uric acid C-reactive protein Black tea and statin therapy Tea polyphenols and biomarkers Cardioprotection and cardiovascular diseases Inflammation a b s t r a c t The effect of black tea on the level of uric acid (UA) and C-reactive proteins (CRP) in humans suscep-tible to ischemic heart diseases was assessed in a prospective randomized controlled study. The study group consumed 9 g of black tea (equivalent to three cups of tea) daily for 12 weeks without additives followed by a 3-week wash-out (with control group consuming equivalent volume of hot water). Black tea consumption induced a highly significant decrease in the high uric acid baseline groups >6 mg/dL by 8.5%; p < 0.05. For men and women in the base line group >7 mg/dL, the decrease was 9.4% and 7.1%, respectively. In the low baseline serum uric acid levels there was a non-significant increase of 3.7% and 15% in men and women, respectively. C-reactive protein in the high risk group >3 mg/L was significantly decreased by 53.4% and 41.1% in men and women, respectively. For the non-supplemented group in this range the changes were 3.7% decrease for men and 2.9% increase for women. Tea supplementation-associated decrease in plasma uric acid and C-reactive protein levels may benefit humans at high risk of cardiovascular events and may augment drug therapy.
No. of Pages Toxicology. 01/2009; xxx.
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ABSTRACT: The potential cytotoxic effect of aggregated Abeta(1-42) to neurons that express classical neurotransmitters, including acetylcholine, gamma-amino butyric acid, catecholamines and serotonin was assessed. The cholinergic system has been the central focus of the therapeutic drug strategies in amyloid-depositing pathologies such as Alzheimer's disease. Aggregated Abeta(1-42) has a multisystem cytotoxic effect causing non-specific reduction in immunoreactivity, dysfunction, or loss of retinal nerve cells. The extent of this was investigated using immunocytochemistry, TUNEL staining for apoptosis, and measurement of cell density as well as retinal surface area. There was a differential acute and/or chronic effect of Abeta on choline acetyltransferase, gamma-aminobutyric acid and 5-tryptamine hydroxylase systems, observed with the increasing time course of 6h to 5 months, and a bilateral/systemic effect. In contrast, the overall pattern of catecholaminergic system, as revealed by tyrosine hydroxylase immunoreactivity of the retina, appears to have remained relatively unaffected by Abeta (however this may reflect neuronal loss due to reduction in the retinal surface). This is the first in vivo evidence in a CNS model to show that not only all major neurotransmitter systems are differentially affected by Abeta aggregates but the effect may vary from one transmitter system to another under the same experimental conditions in situ and in a dose- and time-dependent manner.
Toxicology 12/2008; 256(1-2):92-100. · 3.68 Impact Factor
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ABSTRACT: The role of free radicals in the etiology and development of a wide range of clinical disorders has continued to fuel the suggestion that phenolic antioxidants can offer a realistic promise to reduce the incidence of a number of pathologies involving oxidative stress. In this study, the total phenol, flavonoid, and proanthocyanidin contents of the Mauritian medicinal plants Crinum mauritianum. Lodd. (Asteraceae), Gaertnera psychotroides. DC (Rubiaceae), Psidia terebinthina. A.J. Scott (Asteraceae), and Tylophora coriacea. Marais. (Monimiaceae) were assessed and contrasted with their antioxidant potential. The antioxidant propensity was evaluated by the ability of the extracts to scavenge hypochlorous acid and hydroxyl radical and the ABTS + radical including their abilities to inhibit microsomal lipid peroxidation. The endemic plants Badula multiflora. A. DC. (Myrsinaceae), Croton vaughanii. L. (Euphorbiaceae), Erythroxylum macrocarpum. Lam. (Erythroxylaceae), Ochna mauritiana. Lam. (Ochnaceae), Tambourissa cordifolia. Lorence. (Monimiaceae), and Turraea rigida. Vent. (Meliaceae) were similarly investigated. Badula multiflora. and Erythoxylum macrocarpum. showed highest antioxidant activity in the TEAC and FRAP assay. Badula multiflora., Ochna mauritiana., and Gaertnera psychotroides. were very potent scavengers of hypochlorous acid and inhibited microsomal lipid peroxidation induced by 2,2′-azobis.(2-amidinopropane) hydrochloride (AAPH), suggesting that the inhibition was intrinsically linked to peroxyl radical scavenging. The antioxidant activity of Gaertnera psychotroides., Tylophora coriacea., Psidia terebinthina., and Crinum mauritianum. may account for the therapeutic effects of these extracts, in particular, in conditions characterized by inflammation and oxidative mechanisms. While these polyphenolic-rich endemics are good sources of natural prophylactic antioxidants, there is an urgent need for sustainable conservation programs for their protection.
10/2008; 45(1):9-17.
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ABSTRACT: Osteoporosis is a disease of aging associated with bone loss that often occurs without symptoms until microarchitectural deterioration becomes so significant that bone fracture occurs. The effective microorganism-X (EM-X) is an antioxidant beverage derived from ferment of unpolished rice, sea weeds and papaya with effective microorganisms of lactic acid bacteria, yeast and photosynthetic bacteria (containing minerals, alpha-tocopherol, lycopene, ubiquinone, saponin and flavonoids). The levels of serum estradiol (E(2)) and the bone density of the middle and epiphysis of femurs were assessed in order to determine the effect of EM-X on osteoporosis in ovariectomized rat (an animal model of postmenopausal osteoporosis). EM-X (1 ml/rat/day) was initially administrated by gavage to rats which were then allowed to consume 10% (v/v) EM-X in water freely for 3 months. There was no statistical significance of E(2) level between sham operation group and control group, indicating that sham operation did not affect E(2) level. However, the E(2) levels in the ovariectomized rats tended to increase after treatment of EM-X for 3 months. The bone density of the middle and epiphysis of femur in both sham operation and ovariectomy group decreased with time. Rats receiving EM-X for 3 months after sham operation or ovariectomy had increased bone density of the middle of femur that was statistically significant (P < 0.01 and P < 0.05). The bone density of the epiphysis of femur in both sham operation and ovariectomy group were significantly increased, an outcome highly suggestive of the beneficial effects of EM-X on bone density of the middle and the epiphysis of femur in the rats with or without ovariectomy.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2008; 63(2):114-9. · 2.24 Impact Factor
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ABSTRACT: There is continued interest in the assessment of the bioefficacy of the active principles in extracts from a variety of traditional medicine and food plants in order to determine their impact on the management of a variety of clinical conditions and maintenance of health. The polyphenolic composition and antioxidant potential of Mauritian endemic plants of the Rubiaceae, Ebenaceae, Celastraceae, Erythroxylaceae and Sterculaceae family were determined. The phenolics level of the plant extracts varied from 1 to 75 mg/g FW, the maximum level measured in Diospyros neraudii (Ebenaceae). Coffea macrocarpa showed the highest flavonoids content with 18+/-0.7 mg/g FW. The antioxidant capacity based on the TEAC and FRAP values were strongly related to total phenolics and proanthocyanidins content, while a weaker correlation was observed with (-) gallic acid. Erythroxylum sideroxyloides showed the highest protective effect in the lipid peroxidation systems with IC(50) of 0.0435+/-0.001 mg FW/ml in the Fe(3+)/ascorbate system and 0.05+/-0.002 mg FW/ml in the AAPH system. Cassine orientalis, E. sideroxyloides, Diospyros mellanida and Chassalia coriancea var. johnstonii were weakly prooxidant only at higher concentration greater of 10 g FW/L indicating potential safety. Mauritian endemic plants, particularly the genus Diospyros, are good sources of phenolic antioxidants and potential candidates for the development of prophylactic agents.
Toxicology in Vitro 03/2008; 22(1):45-56. · 2.78 Impact Factor
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ABSTRACT: Antioxidants from plants were known to reduce the oxidative stress by scavenging free radicals, chelating metal ions and reducing inflammation. As increased oxidative stress was implicated in the nigrostriatal dopaminergic neuronal loss in Parkinson's disease (PD), we have assessed whether the plant extracts protects the nigrostriatal dopaminergic neurons in the animal model of PD.
Male adult Sprague-Dawley rats were treated orally between 10 am-11 am each day with the extracts from tangerine peel, grape seeds, cocoa and red clover for four days. One hour after the final dosing, the left medial forebrain bundle was lesioned by infusing the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA; 12 microg) under anaesthesia. Seven days post-lesion, the number of dopaminergic cells in the substantia nigra pars compacta and the levels of dopamine and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striata were quantified and compared with the vehicle-treated groups.
Compared to the unlesioned side, 6-OHDA lesions significantly reduced the number of dopaminergic cells and the levels of dopamine and its metabolites DOPAC and HVA in the vehicle-treated animals. Pretreatment of animals with extracts of tangerine peel (rich in polymethoxylated flavones; 35 mg/kg/day), cocoa-2 (rich in procyanidins; 100 mg/kg/day) and red clover (rich in isoflavones; 200 mg/kg/day) significantly attenuated the 6-OHDA-induced dopaminergic loss. However, no significant protection was seen in animals supplemented with red and white grape seeds (rich in catechins; 100 mg/kg/day), and cocoa-1 (rich in catechins; 100 mg/kg/day).
Pre-treatment of plant extracts rich in polymethoxylated flavones, procyanidins and isoflavones but not catechins protected the nigrostriatal dopaminergic neurons in the rat model of PD.
Journal of the American College of Nutrition 09/2007; 26(4):341-9. · 2.29 Impact Factor
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ABSTRACT: Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.
Biomedecine [?] Pharmacotherapy 09/2007; 61(7):427-34. · 2.00 Impact Factor
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ABSTRACT: Oligonol is a novel catechin-rich biotechnology product. The role of oligonol in modulating intracellular signaling mechanisms was investigated with the view of demonstrating its potential chemopreventive effect and the ability to inhibit cell proliferation using the estrogen-responsive MCF-7 and the estrogen-unresponsive MDA-MB-231 human breast cancer cell lines. Cell survival assay indicated that Oligonol was cytotoxic to both cells. Oligonol triggered apoptosis as revealed by the morphological features typical of nucleus staining and the accumulation of sub-G1 peak. Treatment with 25 microg/ml Oligonol resulted in an activation of caspase-7 and up-regulation of Bad on MCF-7 cells, while the Oligonol (20 microg/ml) induced up-regulation of Bcl-2 protein in a time-response manner on MDA-MB-231 cells. ERK1/2 in both cells were inactivated after Oligonol treatment in a time-dependent manner, and also inactivated upstream MEK1/2. Oligonol triggers apoptosis in MCF-7 and MDA-MB-231 cells through the modulation of pro-apoptotic Bcl-2 family proteins and MEK/ERK signaling pathway.
European Journal of Cancer Prevention 09/2007; 16(4):342-7. · 2.13 Impact Factor
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ABSTRACT: Cisplatin (cis-diaminedichloroplatinum (II) or CDDP) (a widely used platinum-containing anticancer drug) is nephrotoxic and has a low percentage of tolerance in patients during chemotherapy. The active hexose correlated compound (AHCC) is an extract of Basidiomycotina marketed as a supplement for cancer patients due to its nutrients and fibre content and its ability to strengthen and optimize the capacity of the immune system. The possibility that AHCC could reduce the side effects of cisplatin was assessed in the tumor-bearing BALB/cA mice on the basis of the ability to ameliorate the cisplatin-induced body weight loss, anorexia, nephrotoxicity and hematopoietic toxicity. Although cisplatin (8 mg/kg body weight) reduced the size and weight of the solid tumors, supplementation with AHCC significantly enhanced cisplatin-induced antitumor effect in both the size (p<0.05) and weight (p<0.05). Food intake in the cisplatin-treated mice were decreased following commencement of treatment and this remained low compared with the cisplatin-untreated group (control) throughout the experiment period. Supplementation with AHCC increased the food intake in the cisplatin-treated mice. The blood urea nitrogen and serum creatinine concentrations, and the ratio of blood urea nitrogen to serum creatinine were significantly increased in the cisplatin alone treated group compared to the control group. Their increased levels were mitigated by supplementation with AHCC (100 mg/kg body weight) in the cisplatin-treated group. AHCC was also able to modulate the suppression of bone marrow due to cisplatin and the improvement was statistically significant. The histopathological examination of the kidney revealed the presence of cisplatin-induced damage and this was modulated by AHCC treatment. The potential for AHCC to ameliorate the cisplatin-evoked toxicity as well as the chemotherapeutic effect could have beneficial economic implications for patients undergoing chemotherapy with cisplatin.
Toxicology and Applied Pharmacology 07/2007; 222(2):152-8. · 4.45 Impact Factor
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ABSTRACT: Oligonol((R)) is an optimised phenolic product containing catechin-type monomers and lower oligomers of proanthocyanidin that emanate from a technology process which converts polyphenol polymers into oligomers. In a single dose toxicity study administration of Oligonol (2000mg/kg bw) by gavage for 4 weeks was found to be safe with no side effects (such as abnormal behavior and alopecia). Body weight gain and food consumption were within normal range. Oligonol had no observed toxicity at the dose (1/25 of LD(50)) administered for 6 months. This suggests that Oligonol is safe at repeated human intakes of Oligonol in doses lower than 200mg/day. The highest dose used in this study is equal to 12g daily for an adult man with 60kg body weight. The LD(50) was calculated to be 5.0g/kg body weight (95% confidence limit: 3.5-6.4g/kg). Studies conducted on 30 healthy volunteers consuming Oligonol at doses of 100mg/day and 200mg/day for 92 days showed good bioavailability. The biochemical parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. The potential of Oligonol to induce gene mutation (a reverse mutation test) was tested using Salmonella typhimurium TA98, TA100, TA104, TA1535, TA153 and Escherichia coli WP2uvrA. Oligonol was not mutagenic to the tester strains. The lack of toxicity supports the potential use of Oligonol as a food or dietary supplement and for use as an additive in pharmaceutical and cosmetological applications.
Food and Chemical Toxicology 04/2007; 45(3):378-87. · 3.00 Impact Factor
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Volker Mersch-Sundermann,
Theeshan Bahorun,
Thorsten Stahl,
Vidushi S Neergheen,
Muhammad A Soobrattee,
Robert Wohlfarth,
Rosa Sobel,
Hubertus E Brunn,
Tim Schmeiser,
Evelyn Lamy, Okezie I Aruoma
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ABSTRACT: Naturally occurring compounds have protective effects towards mutagens and carcinogens. The leaf extract of Monimiastrum globosum (Bois de Clous), a Mauritian endemic plant from the Myrtaceae family, was studied for its potency to induce DNA damage in human HepG2 hepatoma cells using DNA migration as a biological endpoint in the alkaline single cell gel electrophoresis (SCGE) assay. This was contrasted with the ability to modulate the benzo[a]pyrene (BaP)-dependent DNA damage in human hepatoma cells. M. globosum caused genotoxicity in HepG2 cells at concentrations exceeding 3mg fresh weight (FW) per ml cell culture in the absence of cytotoxicity. Pre-treatment of the cells with 12.2 microg FW/ml to 1.56 mg FW/ml led to a pronounced antigenotoxic effect towards BaP-induced DNA damage. DNA migration (OTM) was reduced by 66%, 81.5% and 74% for 49, 98 and 195 microg FW/ml, respectively. A U-shaped dose-response curve was derived for M. globosum indicating genotoxic effects in high doses and antigenotoxic effects in low doses. M. globosum extract had total phenolics (15 mg/g FW) with flavonoids (aglycones and conjugates: 8 mg/g FW) and proanthocyanidins (3mg/g FW) as major phenolic subclasses. The hydrolysis of conjugated flavonoids yielded the aglycones quercetin (606 microg/g FW) and kaempferol (117.8 microg/g FW) while HPLC-MS/MS analysis of the total extract revealed free flavonoids such as quercetin (19.2 microg/g FW) and myricetin (2.5 microg/g FW). The antioxidant activity of the extract of M. globosum, assessed by the FRAP and TEAC assays yielded values of 275+/-3.82 micromol/g FW and 346+/-4.2 micromol/g FW, respectively.
Toxicology in Vitro 01/2007; 20(8):1427-34. · 2.78 Impact Factor
