Amelioration of Radiation-Induced Damages in Mice by Curcuminoids: The Role of Bioavailability.

PURPOSE: The present study investigated the role of free curcuminoids bioavailability on the relative radioprotective efficacy of natural unformulated curcuminoids. MATERIALS AND METHODS: A food-grade bioavailable formulation of curcuminoids as curcumagalactomannosides (CGM) and unformulated curcuminoids (UC) were employed for the study. Swiss albino mice were randomized into Normal control, Radiation control, Radiation + UC, and Radiation + CGM groups and irradiated with γ-radiation of 6, 8, 10 and 12 Gy. Survival rate, hematological and biochemical parameters, bone marrow cellularity, chromosomal aberrations and histopathology of intestine were followed as a measure of the relative efficacy.Results and Discussion: Oral administration with both UC and CGM at 100 mg/kg. b.wt. produced significant radioprotective effect over the untreated control group of animals. However, CGM treatment was found to provide better clastogenic and genotoxic potential as compared to UC. Further, the histopathology analysis of intestine confirmed the better protective effect of CGM over UC-treated animals. CONCLUSION: The present study demonstrated the positive role of the bioavailability of curcuminoids in the amelioration of radiation-induced damages in mice since CGM treatment exerted better survival rate and radioprotective effect as compared with UC, despite the relatively low concentrations of curcuminoids in CGM (39% w/w).

Comparative neuroprotective effects of native curcumin and its galactomannoside formulation in carbofuran-induced neurotoxicity model.

Toxicity of the pesticide carbofuran (CF) can be alleviated by curcumin, if not for its poor bioavailability. Hence, we investigated the effect of a bioavailable curcumin-galactomannan complex (CGM) on CF-induced neurotoxicity in rats in comparison to that of unformulated standard curcumin (CS). The CF (5 mg/kg b.wt/day) treatment for 90 days produced chronicity model which were treated with either CS or CGM (100 mg/kg b.wt and 250 mg/kg b.wt/day) for another 30 days. Improvement in CF-induced behaviour was evident in endurance, motor co-ordination and pain response on both CS (p < 0.01) and CGM (p < 0.001) supplementation. Amelioration of CF-induced toxicity parameters, oxidative stress, and mitochondrial dysfunction on CS (p < 0.01) and CGM (p < 0.001) supplementation was further confirmed by histopathology of brain and liver tissues. But, CGM was more effective in mitigating CF toxicity, with results comparable to that of normal. Hence, CGM might be superior in toxicity management against CF.

Beyond the flavor: A green formulation of Ferula asafoetida oleo-gum-resin with fenugreek dietary fibre and its gut health potential.

Albeit the fact that asafotida is a popular kitchen spice and Indian folklore medicine for gut disorders, its consumption at physiologically relevant dosage is greatly challenged by the unpleasant flavor characteristics. Herein we report a green approach to derive stable powder formulations of asafoetida gum with minimized taste and odor suitable for dietary applications and gut health-related disorders. Employing a water based ultrasound mediated gel-phase dispersion of asafoetida gum on fenugreek derived soluble galactomannan fibre matrix. Microencapsulated particles (1 ± 0.3 µm) of asafoetida was prepared as water dispersible free flowing powder (Asafin). Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), accelerated stability and in vitro dissolution studies confirmed the stability, sustained release and microencapsulated structure of Asafin. Further investigations revealed significant (p < 0.01) reduction in acetic acid-induced writings and inhibition of ethanol-induced ulcer (94.1%) in rats orally administered with Asafin at 250 mg kg-1 b.w. Asafin also exhibited anti-inflammatory effects (p < 0.01), in acute and chronic paw edema mice models. The safety of Asafin was further demonstrated by acute toxicity studies at 4 g kg-1 b.w. and by 28 days of sub-acute toxicity studies at 2.0 g kg-1 b.w.

Protective Effect of Curcumin Against Carbofuran-Induced Toxicity in Wistar Rats.

Pesticide carbofuran (Furadan) is known to be an inhibitor of nerve impulses by its inhibition of acetylcholinesterase. Oral administration of carbofuran also produced tissue damage as evidenced by the increased the activities of creatine kinase (CK), lactate dehydrogenase (LDH), and gamma glutamyl transferase (γ-GT) in tissues and serum. Against carbofuran, curcumin restored the activities of acetylcholinesterase, LDH, CK and γ- GT in animals. Curcumin also restored the reduced mitochondrial enzymes in rat liver caused by carbofuran. Liver carbohydrate metabolizing enzyme hexokinase was increased, and glucose 6-phosphate dehydrogenase, fructose 1,6 diphosphatase, and glucose 6-phosphatase decreased after carbofuran treatment. Treatment with curcumin improved these enzyme activities in the liver. Carbofuran exposure resulted in increased lipid peroxidation (LPO), hydroperoxides, and conjugated diene in liver. Administration of curcumin during carbofuran administration lowered LPO, conjugated diene, and hydroperoxides. Moreover, levels of superoxide dismutase, glutathione peroxidase, catalase, and glutathione, which were significantly decreased after carbofuran exposure, were increased by curcumin administration. Marked impairment in the motor function was seen following carbofuran administration. Curcumin treatment significantly improved the carbofuran-induced neurobehavioral difficulties. These results indicate the ameliorating activity of carbofuran toxicity by curcumin.

Amelioration of Doxorubicin-Induced Cardiac and Renal Toxicity by Oxycarotenoid Lutein and Its Mechanism of Action.

We set out to determine the effect of oxycarotenoid lutein on reducing cardiac and renal toxicity induced by doxorubicin (DXR). We started with oral administration in rats of lutein for 15 d before administering DXR (30 mg/kg body weight, intraperitoneally, in a single dose). Animals in all groups were sacrificed 24 h after DXR administration. Serum markers of cardiac injury lactate dehydrogenase, creatine phosphokinase, serum glutamate oxaloacetate transaminase, and serum glutamate pyruvate transaminase increased drastically after DXR but decreased after lutein treatment (p < 0.001). Elevated serum urea and creatinine in DXR-treated rats were reduced by lutein treatment (p < 0.001). Lutein increased superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels in cardiac and renal tissues of DXR-treated rats. Pretreatment of lutein reduced DXR-induced rise of oxidative stress markers including lipid peroxidation, tissue hydroperoxides, and conjugated dienes in cardiac and renal tissue. These findings were supported by electrocardiogram measurements and histopathological analyses. Results confirmed the protection of lutein against cardiac and renal toxicity induced by DXR in rats.

Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P < 0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as compared with the standard curcumin group, when monitored by SF-36, Perceived Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the quality of life was further correlated with the significant enhancement in endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P < 0.001). Further comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations.

Protection against Whole Body γ-Irradiation Induced Oxidative Stress and Clastogenic Damage in Mice by Ginger Essential Oil.

Radioprotective effects of ginger essential oil (GEO) on mortality, body weight alteration, hematological parameters, antioxidant status and chromosomal damage were studied in irradiated mice. Regression analysis of survival data in mice exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively, with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma-irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally) significantly ameliorated decreased hematological and immunological parameters. Radiation induced reduction in intestinal tissue antioxidant enzyme levels such as superoxide dismutase, catalase, glutathione peroxidase and glutathione was also reversed following administration of GEO. Tissue architecture of small intestine which was damaged following irradiation was improved upon administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO significantly decreased the formation of micronuclei, increased the P/N ratio, inhibited the formation of chromosomal aberrations and protected agaisnt cellular DNA damage in bone marrow cells as revealed by comet assay. These results are supportive of use of GEO as a potential radioprotective compound.

Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies.

Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol), as assessed by oral acute (5 g/kg b.wt. for 14 days) and subchronic (0.25, 0.5 and 1 g/kg b.wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of Clovinol did not result in any toxicologically significant changes in clinical/behavioural observations, ophthalmic examinations, body weights, organ weights, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals, indicating the no observed-adverse-effect level (NOAEL) as 1000 mg/kg b.wt./day; the highest dose tested. Terminal necropsy did not reveal any treatment-related histopathology changes. Clovinol did not show genotoxicity when tested on TA-98, TA-100 and TA-102 with or without metabolic activation; rather exhibited significant antimutagenic potential against the known mutagens, sodium azide, NPD and tobacco as well as against 2-acetamidoflourene, which needed metabolic activation for mutagenicity.

Amino acids in sandal (Santalum album L) with special reference to cis-4-hydroxy-l-proline and sym. homospermidine.

Sandal (Santalum album L) contains several interesting amino acids and amines which are not seen in other plants. This includes cis-4-hydroxy-l-proline in free form in leaves, flowers and seeds while trans-4-hydroxy-l-proline in bound form. Traces of 3, 4 dehydroproline is also detected in sandal leaves. Biosynthesis of cis-4-hydroxy proline indicates that hydroxylation taken place at proline present in peptidyl form especially bound to glutamic acid and aspartic acid. Pyrrolizidine-2-carboxylic acid an interesting isatin positive heterocyclic compound is also present in sandal leaves. Sandal also contains sym. homospermidine which is not present in any other plants till today. Biosynthesis of sym. homospermidine goes by a unique pathway of putrescine oxidation, Schiff base formation, condensation and reduction. Moreover sandal leaves contain γ-glutamyl derivative of the lachrymatory precursor of onion, γ-glutamyl-S-propenyl cysteine superoxide. This review summarizes the studies on the amino acids in sandal.

Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action.

CONTEXT: meso-Zeaxanthin (MZ) is a xanthophyll carotenoid with profound antioxidant activity. OBJECTIVE: Oxidative stress plays a decisive role in numerous degenerative diseases including cancer. The present study evaluates anti-inflammatory effect of MZ. MATERIALS AND METHODS: Balb/c mice were treated with different doses of MZ (50 and 250 mg/kg b.wt, orally) 5 d before subcutaneous injection of carrageenan (1%), dextran (1%), and formalin (2%). Paw edema formation in MZ-treated and -untreated animals was measured using vernier calipers. Anti-inflammatory activity of MZ against lipopolysaccharide (LPS)-induced inflammatory model was studied by culturing macrophages in the presence and absence of LPS (5 µg/ml) and different concentrations of MZ (5, 10, and 25 µg/ml). After 24 h, the effect of MZ on pro-inflammatory cytokine levels in macrophages was analyzed by ELISA and its effect on various inflammatory genes was studied by RT-PCR. RESULTS: MZ administration at different doses significantly (p < 0.001) inhibited paw edema induced by carrageenan, dextran, and formalin in mice. MZ also exhibited profound anti-inflammatory effect against LPS-induced inflammation in macrophages. Increased production of nitric oxide, C-reactive proteins, and various pro-inflammatory cytokines (TNF-α, interleukin-1ß, and interleukin-6) in LPS-stimulated macrophages was significantly reduced by MZ treatment. Moreover, LPS-stimulated up-regulated mRNA expression of various inflammatory mediator genes like COX-2, TNF-α, and iNOS was down-regulated by MZ administration. DISCUSSION AND CONCLUSION: MZ has potent anti-inflammatory effect which can be due to its down-regulated expression of various inflammatory mediator genes. Since cancer is considered as an inflammatory disease, the present study points towards the importance of MZ in chemo-preventive strategy.

Safety and anti-ulcerogenic activity of a novel polyphenol-rich extract of clove buds (Syzygium aromaticum L).

Despite the various reports on the pharmacology of Clove bud [Syzygium aromaticum]-derived essential oil and its major component eugenol, systematic information on the bioactivity of clove polyphenols is very limited. Clove buds being one of the richest sources of dietary polyphenols with many traditional medicinal uses, the present contribution attempted to derive their standardized polyphenol-rich extracts as a water soluble free flowing powder (Clovinol) suitable for functional food applications, without the issues of its characteristic pungency and aroma. The extract was characterized by electrospray ionization-time of flight mass spectrometry (ESI-TOF-MS), and investigated for in vivo antioxidant, anti-inflammatory and anti-ulcerogenic activities. Clovinol showed significant antioxidant and anti-inflammatory effects as measured by cellular antioxidant levels, and the ability to inhibit carrageenan-induced paw swelling in mice. Further investigations revealed its significant anti-ulcerogenic activity (>97% inhibition of ethanol-induced stomach ulcers in Wistar rats when orally administered at 100 mg per kg b.w.) and up regulation of in vivo antioxidants such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Clovinol also reduced the extent of lipid peroxidation among ulcer induced rats, indicating its usefulness in ameliorating oxidative stress and improving gastrointestinal health, especially upon chronic alcohol consumption. The extract was also shown to be safe and suitable for further investigations and development upon acute toxicity studies at 5 g per kg body weight and 28 days of repeated dose toxicity studies at 2.5 g per kg b.w.

Enhanced bioavailability and safety of curcumagalactomannosides as a dietary ingredient.

In spite of the various bioavailable formulations of curcumin for pharma and dietary supplement applications, food grade formulations suitable as a dietary ingredient, and capable of providing significant levels of plasma curcumin, are limited. The present contribution describes the safety and oral bioavailability of a novel water soluble formulation of curcumin, curcumagalactomannosides (CGM), when used as a dietary ingredient in selected food items. CGM was prepared using a food grade hydrocolloid (galactomannans) derived from the kitchen spice fenugreek (Trigonella foenum graccum), without using any synthetic excipients. The safety of the formulation was assessed through acute and subchronic toxicity studies on Wistar rats and genotoxicity studies. The efficacy of CGM as a bioavailable dietary ingredient was assessed by successfully preparing various food items and by measuring the post-blood plasma curcumin levels at various time intervals after the consumption of food items. High performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) and electrospray ionization tandem mass spectrometer (ESI-MS/MS) was employed for the quantification of plasma curcuminoids. It was observed that CGM is safe and suitable for further development and clinical studies, with a no observable adverse effect level (NOAEL) up to 2.0 g kg⁻¹ per day b.wt. CGM was found to offer seven to ten times higher bioavailability of curcumin in humans, when incorporated into various food/beverage items at 100 mg CGM per serving size, as compared to the standard unformulated curcumin.

Gastroprotective activity of essential oils from turmeric and ginger.

BACKGROUND: Turmeric (Curcuma longa) and ginger (Zingiber officianale) are widely used in Asian countries as traditional medicine and food ingredients. In the present study, we have evaluated the gastroprotective activity of turmeric essential oil (TEO) and ginger essential oil (GEO) in rats. METHODS: Turmeric and ginger were evaluated for their antiulcer activity against ethanol-induced ulcers in male Wistar rats at different doses: 100, 500 and 1000 mg/kg body weight. Ethanol was used to induce gastric ulcer in Wistar rats. Parameters such as ulcer index, histopathology and levels of antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and glutathione (GSH) levels were measured to assess the degree of protection produced by the essential oils. RESULTS: TEO and GEO inhibited ulcer by 84.7% and 85.1%, respectively, as seen from the ulcer index. Reduced antioxidant enzymes such as GPx, SOD, catalase and GSH produced by alcohol administration were significantly (p<0.001) increased by simultaneous administration of TEO and GEO. Histopathological examination showed that ethanol-induced lesions such as necrosis, erosion and hemorrhage of the stomach wall were significantly reduced after oral administration of essential oils. CONCLUSIONS: RESULTS suggest that TEO and GEO could reduce the gastric ulcer in rat stomach as seen from the ulcer index and histopathology of the stomach. Moreover, oxidative stress produced by ethanol was found to be significantly reduced by TEO and GEO.

Chemopreventive activity of turmeric essential oil and possible mechanisms of action.

This study aimed to evaluate the antimutagenic and anticarcinogenic activity of turmeric essential oil as well as to establish biochemical mechanisms of action. Antimutagenicity testing was accomplished using strains and known mutagens with and without microsomal activation. Anticarcinogenic activity was assessed by topical application of 7, 12 - dimethylbenz[a]anthracene (DMBA) as initiator and 1% croton oil as promoter for the induction of skin papillomas in mice. Inhibition of p450 enzymes by TEO was studied using various resorufins and aminopyrene as substrate. Turmeric essential oil (TEO) showed significant antimutagenic activity (p<0.001) against direct acting mutagens such as sodium azide (NaN3), 4-nitro-O-phenylenediamine (NPD) and N-methyl- N-nitro N'nitrosoguanine (MNNG). TEO was found to have significant antimutagenic effect (>90%) against mutagen needing metabolic activation such as 2-acetamidoflourene (2-AAF). The study also revealed that TEO significantly inhibited (p<0.001) the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by TEO application. Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1, CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens. Results indicated that TEO is antimutagenic and anticarcinogenic and inhibition of enzymes (p450) involved in the activation of carcinogen is one of its mechanisms of action.

Antimutagenic potential and modulation of carcinogen-metabolizing enzymes by ginger essential oil.

Essential oil extracted from ginger (GEO) was evaluated for its mutagenicity to Salmonella typhimurium TA 98, TA 100, TA 102, and TA 1535 strains with and without microsomal activation. GEO was found to be non-mutagenic up to a concentration of 3 mg/plate. It was also assessed for antimutagenic potential against direct acting mutagens such as sodium azide, 4-nitro-o-phenylenediamine, N-methyl-N'-nitro-N-nitrosoguanidine, tobacco extract, and 2-acetamidoflourene, which needs microsomal activation. GEO significantly inhibited (p < 0.001) the mutagenicity induced by these agents in a concentration-dependent manner. The effect of GEO to modulate the action of phase I carcinogen-metabolizing enzymes was investigated by studying its effect on various isoforms of microsomal cytochrome P450 enzymes. Significant inhibition of CYP1A1, CYP1A2, and CYP2B1/2, aniline hydroxylase (an indicator of CYP2E1 activity), and aminopyrine-N-demethylase (indicator of CYP1A, 2A, 2B, 2D, and 3A activity) was shown by GEO both in vitro and in vivo. GEO gave an IC50 value of 30, 57.5, and 40 µg for CYP1A1, CYP1A2, and CYP2B1/2, respectively, 55 µg for aniline hydroxylase, and 37.5 µg for aminopyrene-N-demethylase. GEO also significantly increased the levels of phase II carcinogen-metabolizing enzymes uridine 5'-diphospho-glucuronyl transferase and glutathione-S-transferase in vivo indicating the use of GEO as an antimutagen and as a potential chemopreventive agent.

Antioxidant, anti-inflammatory and antinociceptive activities of essential oil from ginger.

Chemical compositions of ginger oil as well as its antioxidant, anti-inflammatory and antinociceptive potential were evaluated in the present study. The main constituents as detected by GC/MS analysis was alpha-zingiberene which constituted 31% of the total area, ar-curcumene (15.4%) and a -sesquiphellandrene (14.02%). Ginger oil scavenged superoxide, DPPH, hydroxyl radicals and inhibited tissue lipid peroxidation in vitro. Intraperitoneal administration of ginger oil was found to inhibit phorbol-12-myristate-13-acetate induced superoxide radicals elicited by macrophages. Oral administration of ginger oil for one month, significantly increased superoxide dismutase, glutathione and glutathione reductase enzymes level (P < 0.001) in blood of mice and glutathione-S-transferase, glutathione peroxidase and superoxide dismutase enzymes in liver. Ginger oil produced significant reduction in acute inflammation produced by carrageenan and dextran and formalin induced chronic inflammation (P < 0.001). It also exhibited significant reduction in acetic acid induced writhing movements (P < 0.001). The present report revealed that ginger oil possesses antioxidant activity as well as significant anti-inflammatory and antinociceptive property.

Anticarcinogenic activity of meso-zeaxanthin in rodents and its possible mechanism of action.

Anticarcinogenic activity of meso-zeaxanthin (MZ), a xanthophyll carotenoid with profound antioxidant activity, was evaluated against 3-methylcholanthrene (3-MC)-induced sarcoma in mice. Oral administration of MZ at different doses significantly increased tumor latency period. In 3-MC control group, animals started developing sarcoma on 6th week. However animals treated with 3-MC and MZ (50 and 250 mg/kg b.wt) started developing sarcoma only on 15th and 18th week, respectively. Survival of tumor-bearing mice was significantly increased by MZ treatment. Animals in 3-MC control group started dying due to tumor burden from 8th week. All animals treated with MZ (50 and 250 mg/kg b.wt) along with 3-MC were found to be alive even after 16 and 20 wk, respectively. Oral administration of MZ inhibited different CYP450 isoenzymes like CYP1A1 (PROD), CYP1A2 (MROD), and CYP2B1/2 (EROD), which are involved in carcinogen metabolism in a dose-dependent manner. Moreover, levels of phase II enzymes like UDP-glucuronyl transferase and glutathione-S-transferase, which are involved in detoxification of carcinogens, were significantly increased by MZ treatment. Results indicated that mode of action of MZ may be through inhibition of carcinogen activation coupled with enhancement of detoxification process. MZ may also inhibit promotion phases of carcinogenesis by its antioxidant activity.

Carotenoid lutein protects the kidney against cisplatin-induced acute renal failure.

Cisplatin is one of the most potent anticancer drugs available for the treatment of a variety of tumors. One of the side effects of this drug is nephrotoxicity. Current research evidence indicates that the renal toxicity is mainly due to the reactive oxygen molecules generated by cisplatin. In the present study, we evaluated the nephroprotective activity of lutein, a non-toxic carotenoid with strong antioxidant activity, to reduce cisplatin-induced renal damage in mice. Serum urea and creatinine levels in the cisplatin-induced mice were significantly elevated compared to those of the control group, and nephrotoxicity was reduced by the lutein treatments (P<0.01). In the cisplatin-treated control group as well as in the vehicle control group, antioxidant enzymes in the kidney, such as superoxide dismutase, as well as catalase activity and level of reduced glutathione were reduced, and the level of malondialdehyde was elevated. Antioxidant enzymes were significantly increased by lutein treatment, and the level of malondialdehyde declined significantly in lutien-treated mice. White blood cell count and bone marrow cellularity, which were significantly reduced in the cisplatin-treated group, were also significantly elevated in all lutein-treated groups (P<0.001). The results of the study show that lutein effectively protected the kidneys of mice treated with cisplatin; these results are also supported by the histopathologies of the kidney tissues of treated mice.

Amelioration of radiation-induced damages in mice by carotenoid meso-zeaxanthin.

PURPOSE: The present study was undertaken to evaluate the radioprotective effect of meso-zeaxanthin, a xanthophyll carotenoid with profound antioxidant activity. MATERIALS AND METHODS: Swiss albino mice were treated with different doses of meso-zeaxanthin (50 and 250 mg/kg body weight, orally) five days before irradiation and sacrificed at different time points. The protective effects of meso-zeaxanthin on mortality, haematological parameters, bone marrow cellularity and gastrointestinal system of irradiated mice were studied. The anti-genotoxic action of meso-zeaxanthin was studied by measuring micronuclei formation, chromosomal aberrations and DNA damage (comet assay). RESULTS: Meso-zeaxanthin administration significantly increased the lifespan of irradiated mice and reduced myelosuppression as evident from increases in white blood cell counts, bone marrow cellularity and the number of maturing monocytes when compared to the myelosuppression in radiation control animals. Meso-zeaxanthin significantly elevated the radiation-induced reduction in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione in both liver and intestinal mucosa. The carotenoid-treated animals showed a profound reduction in genotoxic activity which was apparent in decreases in micronuclei formation and chromosomal aberrations. Irradiation also induced damage to cellular DNA as was obvious from increases in comet parameters like tail DNA%, tail moment, tail length and Olive tail moment in the radiation control group. These parameters were decreased by meso-zeaxanthin treatment. CONCLUSION: Results indicated a radioprotective potential of meso-zeaxanthin.

Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.