Manjeshwar Shrinath Baliga

The evaluation of the radioprotective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to γ-radiation

The effect of 0, 5, 6.25, 10, 12.5, 20, 25, 40, 50 and 80 mg/kg b. wt. of aqueous extract of triphala (an Ayurvedic herbal medicine) administrered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma-radiation. Treatment of mice with different doses of triphala consecutively for five days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. The highest protection against GI (gastrointestinal) death was observed for 12.5 mg/kg triphala, where a highest number of survivors were reported up to 10 days post-irradiation. While 10 mg/kg triphala i.p. provided the best protection as evidenced by the highest number of survivors after 30 days post-irradiation in this group when compared with the other doses of triphala. Toxicity study showed that triphala was non-toxic up to a dose of 240 mg/kg, where no drug-induced mortality was observed. The LD50 dose i.p. of triphala was found to be 280 mg/kg b. wt. Our study demonstrates the ability of triphala as a good radioprotective agent and the optimum protective dose of triphala was 1/28 of its LD50 dose.

Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation

Abstract Jagetia, G. C., Baliga, M. S., Venkatesh, P. and Ulloor, J. N. Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation. Radiat. Res. 160, 584–592 (2003). The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6–12 Gy of γ radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 150 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in the lipid peroxidation and depletion of GSH on day 31 postirradiation; both effects were lessened by pretreatment with ZOE. ZOE also had a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and Candida albicans.

Syzygium cumini (Jamun) reduces the radiation-induced DNA damage in the cultured human peripheral blood lymphocytes: a preliminary study.

The effects of various concentrations (0.0, 1.56, 3.125, 6.25, 12.5, 25, 50 and 100 microg/ml) of the leaf extract of Syzygium cumini Linn. or Eugenia cumini (SC; black plum, Jamun, family Myrtaceae) was studied on the alteration in the radiation-induced micronuclei formation in the cultured human peripheral blood lymphocytes. Treatment of lymphocytes to various concentrations of SC resulted in a dose dependent increase in the micronuclei-induction, especially after 25-100 microg/ml extract. The exposure of human lymphocytes to various concentrations of SC extract before 3 Gy gamma-irradiation resulted in a significant decline in the micronuclei-induction at all the drug doses when compared with the non-drug treated irradiated cultures. A nadir in MNBNC frequency was observed for 12.5 microg/ml drug concentration, where the MNBNC frequency was approximately fourfold lower than that of the non-drug treated irradiated cultures. Therefore, this dose may be considered as an optimum dose for radiation protection. Our study demonstrates that the leaf extract of S. cumini, a plant traditionally used to treat diabetic disorders protects against the radiation-induced DNA damage.

Evaluation of the radioprotective effect of bael leaf (Aegle marmelos) extract in mice

Purpose: To investigate the radioprotective activity of a leaf extract of bael leaf (Aegle marmelos) (AME) in mice exposed to different doses of γ‐radiation. Materials and methods: The acute toxicity of AME was evaluated in Swiss albino male mice administered various intraperitoneal single doses of AME. For radioprotection studies, mice were administered different doses, 0, 5, 10, 15, 20 or 40 mg kg−1, of AME or sterile physiological saline intraperitoneally once daily consecutively for 5 days before exposure to 10 Gy 60Co γ‐radiation or five doses of 15 mg kg−1 AME before exposure to 6, 7, 8, 9, 10 or 11 Gy. The animals were monitored for symptoms of radiation sickness and mortality up to 30 days post‐irradiation. Glutathione and lipid peroxidation were estimated in the surviving animals of both groups on day 31 post‐irradiation. Results: AME was non‐toxic up to a single dose of 1750 mg kg−1. The optimum radioprotective dose was five consecutive doses of 15 mg kg−1 AME, where the highest survival to 10 Gy radiation was observed. The irradiation caused a dose‐dependent decline in survival, while treatment of mice with AME enhanced survival. The dose reduction factor was 1.15. Irradiation caused a dose‐dependent decline in the level of glutathione accompanied by an elevation in lipid peroxidation. AME pretreatment arrested glutathione decline and lipid peroxidation significantly. Conclusion: AME treatment reduced the symptoms of radiation‐induced sickness and increased survival. The radioprotective action might be due to free‐radical scavenging and arrest of lipid peroxidation accompanied by an elevation in glutathione.

Triphala, Ayurvedic Formulation for Treating and Preventing Cancer: A Review

BACKGROUND Triphala (Sanskrit tri = three and phala = fruits), composed of the three medicinal fruits Phyllanthus emblica L. or Emblica officinalis Gaertn., Terminalia chebula Retz., and Terminalia belerica Retz. is an important herbal preparation in the traditional Indian system of medicine, Ayurveda. Triphala is an antioxidant-rich herbal formulation and possesses diverse beneficial properties. It is a widely prescribed Ayurvedic drug and is used as a colon cleanser, digestive, diuretic, and laxative. Cancer is a major cause of death, and globally studies are being conducted to prevent cancer or to develop effective nontoxic therapeutic agents. Experimental studies in the past decade have shown that Triphala is useful in the prevention of cancer and that it also possesses antineoplastic, radioprotective and chemoprotective effects. CONCLUSIONS This review for the first time summarizes these results, with emphasis on published observations. Furthermore, the possible mechanisms responsible for the beneficial effects and lacunas in the existing knowledge that need to be bridged are also discussed.

Influence of the leaf extract of Mentha arvensis Linn. (mint) on the survival of mice exposed to different doses of gamma radiation.

Background: The aim of the present study was to evaluate the radioprotective effect of Mentha arvensis (mint) on the survival of mice exposed to various doses of whole-body gamma radiation. Material and Methods: The radioprotective effect of various doses (0, 2.5, 5, 10, 20, 40 and 80 mg/kg body weight) of chloroform extract of mint (Mentha arvensis Linn.) was studied in mice exposed to 10 Gy gamma radiation. Results: The 10 mg/kg of mint extract was found to afford best protection as evidenced by the highest number of survivors in this group at 30 days post-irradiation, and further experiments were carried out using this dose of mint extract. The mice treated with 10 mg/kg body weight mint extract or oil were exposed to 6, 7, 8, 9 and 10 Gy of gamma radiation and observed for the induction of radiation-sickness and mortality up to 30 days post-irradiation. The mint extract pretreatment was found to reduce the severity of symptoms of radiation sickness and mortality at all exposure doses and a significant increase in the animal survival was observed when compared with the oil + irradiation group. All of the animals that were treated with 10 mg/kg mint extract and then exposed to 7 Gy irradiation were protected against the radiation-induced mortality when compared with the concurrent oil + irradiation group, in which 20% animals died by 30 days post-irradiation. The mint extract treatment protected the mice against the gastrointestinal death as well as bone marrow deaths. The DRF was found to be 1.2. The drug was non-toxic up to a dose of 1 000 mg/kg body weight, the highest drug that could be tested for acute toxicity. Conclusion: From our study it is clear that mint extract provides protection against the radiation-induced sickness and mortality and the optimum protective dose of 10 mg/kg is safe from the point of drug-induced toxicity.Hintergrund: Ziel der vorliegenden Studie war es, den radioprotektiven Effekt von Mentha arvensis (Minze) auf das Überleben von Mäusen nach unterschiedlichen Dosen einer Ganzkörperbestrahlung zu untersuchen. Material und Methoden: Der radioprotektive Effekt verschiedener Dosen (0, 2,5, 5, 10, 20, 40 und 80 mg/kg Körpergewicht) eines Chloroformextraktes der Minze (Mentha arvensis Linn.) wurde bei Mäusen nach Exposition mit 10 Gy Gammabestrahlung untersucht. Ergebnisse: Eine Konzentration von 10 mg/kg des Minzeextraktes zeigte die beste Radioprotektion, da in dieser Gruppe die höchste Anzahl von Überlebenden 30 Tage nach Bestrahlung gefunden wurde. Die weiteren Experimente wurden daher mit dieser Dosis des Minzeextraktes durchgeführt. Die Mäuse wurden mit einer Konzentration von 10 mg/kg Körpergewicht Minzeextrakt oder mit Öl behandelt und einer Gammabestrahlung mit einer Dosis mit 6, 7, 8, 9 und 10 Gy ausgesetzt und anschließend bezüglich der Induktion von radiogenem Erbrechen und Mortalität bis 30 Tage nach Bestrahlung beobachtet. Die Minzeextraktvorbehandlung konnte die Schwere des radiotherapieinduzierten Erbrechens und die Mortalität bei allen Bestrahlungsdosen reduzieren. Es wurde eine signifikante Verbesserung des Überlebens im Vergleich zu den allein mit Ö vorbehandelten Mäusen beobachtet. Alle Tiere, die mit 10 mg/kg Minzeextrakt vorbehandelt wurden und anschließend einer 7-Gy-Bestrahlung ausgesetzt wurden, überlebten, während in der Gruppe der mit Öl vorbehandelten Tieren 20% nach 30 Tagen gestorben waren. Die Minzeextraktbehandlung schützte die Mäuse gegen den Tod sowohl durch gastrointestinale als auch Knochenmarktoxizität. Die DRF betrug 1,2. Die Substanz war bis zu einer Dosis von 1 000 mg/kg Körpergewicht nicht toxisch. Schlussfolgerung: Nach den Studienergebnissen ist klar, dass Minzeextrakt eine Protektion gegen radiotherapieinduziertes Erbrechen und die Mortalität mit einer optimalen protektiven Dosis von 10 mg/kg Körpergewicht ermöglicht und in dieser Dosis auch ohne Toxizität eingesetzt werden kann.

Modulation of doxorubicin-induced genotoxicity by Aegle marmelos in mouse bone marrow: a micronucleus study.

The effect of various concentrations of Aegle marmelos (AME) on the doxorubicin (DOX)-induced genotoxic effects in mice bone marrow was studied. Treatment of mice with different concentrations of DOX resulted in a dose-dependent elevation in the frequency of micronucleated polychromatic (MPCE) as well as normochromatic (MNCE) erythrocytes in mouse bone marrow. The frequencies of MPCE and MNCE increased with scoring time, and the greatest elevation for MPCE was observed at 48 hours post-DOX treatment, whereas a maximum increase in MNCE was observed at 72 hours post-DOX treatment. This increase in MPCE and MNCE was accompanied by a decline in the polychromatic erythrocytes–normochromatic erythrocytes (PCE/NCE) ratio, which showed a DOX-dose-dependent decline. Treatment of mice with 200, 250, 300, 350, and 400 mg/kg body weight of AME, orally once daily for 5 consecutive days before DOX treatment, significantly reduced the frequency of DOX-induced micronuclei accompanied by a significant elevation in the PCE/NCE ratio at all scoring times. The greatest protection against DOX-induced genotoxicity was observed at 350 mg/kg AME. The protection against DOX-induced genotoxicity by AME may be due to inhibition of free radicals and increased antioxidant status.

Fruit Extract of Aegle marmelos Protects Mice Against Radiation-Induced Lethality

The radioprotective effect of a hydroalcoholic extracted material from the fruit of Aegle marmelos (AME) was studied in mice exposed to different doses of γ radiation. The optimum dose for radioprotection was determined by administering 0, 5, 10, 20, 40, or 80 mg/kg body weight of AME intraperitoneally (ip) once daily, consecutively for 5 days before exposure to 10 Gy of γ radiation. A total of 20 mg/kg of AME for 5 consecutive days before irradiation was found to afford maximum protection as evidenced by the highest number of survivors after 30 days postirradiation. Animals from all groups were monitored for 30 days postirradiation for development of symptoms of radiation sickness and mortality. Treatment of mice with AME before exposure to different doses of γ radiation reduced the severity of symptoms of radiation sickness and mortality with all exposure doses. This was accompanied by an increase in number of survivors in the AME + irradiation group when compared with the concurrent sterile physiological saline (SPS) + irradiation group. AME pretreatment protected mice against the gastrointestinal as well as bone marrow deaths, as evidenced by the greater number of survivors on day 10 or 30, respectively. LD50/30 was found to be 8.2 Gy for the SPS + irradiation group, while it was 8.8 Gy for AME + irradiation. The dose-reduction factor (DRF) was found to be 1.1 for AME + irradiation group. The acute toxicity study of AME showed that it was nontoxic up to a dose of 6 g/kg body weight, the highest drug dose that could be administered. Irradiation of animals resulted in a dose-dependent elevation in lipid peroxidation in liver, kidney, stomach, and intestine of mice. Conversely, GSH concentration declined in a dose-dependent manner. Treatment of animals with AME before irradiation caused a significant decrease in the lipid peroxidation accompanied by a significant elevation in the GSH concentration in liver, kidney, stomach, and intestine of mice determined at 31 days postirradiation.

Zingiber officinale (Ginger) as an Anti-Emetic in Cancer Chemotherapy: A Review

Despite significant advances and development of novel anti-emetics, nausea and vomiting (emesis) is a major side-effect of cancer chemotherapy. At times, severe nausea and vomiting may also lead to reduction in adherence to the treatment regimen, and this will concomitantly affect the patients survival. The rhizome of Zingiber officinale, commonly known as ginger, is globally an important spice. It has been used for centuries in the Indian, Chinese, Arabic, Tibetan, Unani, and Siddha systems of traditional medicine to treat nausea and vomiting induced by different stimuli. Preclinical studies with experimental animals (dogs and rats) have shown that the various extracts of ginger and the ginger juice possess anti-emetic effects against chemotherapy-induced nausea and vomiting. Gingerol, the active principle, is also shown to possess anti-emetic effects in minks. However, with regard to humans, while most studies have been supportive of the preclinical observations, a few have been contradictory. The exact mechanism responsible for the anti-emetic effects of ginger is unknown; however, the ginger phytochemicals, especially 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, may function as a 5-hydroxytryptamine (5-HT3) antagonist, NK1 antagonist, antihistaminic, and possess prokinetic effects. The present review for the first time attempts to address the anti-emetic observations and the variability in response of the anti-emetic effects of ginger in cancer chemotherapy. An attempt is also made to address the lacunae in the published studies and emphasize aspects that need further investigations for ginger to be of use in clinics as an anti-emetic agent in the future.

Effect of Sapthaparna (Alstonia scholaris Linn) in modulating the benzo(a)pyrene-induced forestomach carcinogenesis in mice

The chemopreventive effect of various doses of hydroalcoholic extract of Alstonia scholaris (ASE) was studied on the benzo(a)pyrene (BaP) induced forestomach carcinoma in female mice. The treatment of mice with different doses, i.e. 1, 2 and 4 mg/ml ASE in drinking water before, during and after the treatment with carcinogen, exhibited chemopreventive activity. The highest activity was observed for 4 mg/ml ASE, where the tumor incidence (93.33%) was reduced by 6.67%. Similarly, the tumor multiplicity reduced (61.29%) significantly (P<0.02) at 4 mg/ml in the pre-post-ASE treated group. However, the pre or post-treatment of mice with 4 mg/ml ASE did not show chemopreventive activity. These findings are corroborated by micronucleus assay, where treatment of mice with ASE before, during and after carcinogen treatment reduced the frequency of micronuclei (MN) in the splenocytes in a dose dependent manner. The MN frequency reached a nadir at 4 mg/ml ASE, the highest drug dose which showed maximum chemopreventive action. The ASE treatment not only reduced the frequency of splenocytes bearing one MN but also cells bearing multiple MN indicating the efficacy of ASE in inhibiting mutagenic changes induced by BaP. The pre or post-treatment of mice with 4 mg/ml ASE also significantly reduced the frequency of BaP-induced MN in the splenocytes of treated animals.