Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

Radiomodulatory and free-radical scavenging activity of the fractionated aquo-alcoholic extract of the adaptogenic nutraceutical (Rhodiola imbricata)--a comparative in vitro assessment with ascorbate.

OBJECTIVE: Immense interest has been generated in recent years for the development of drugs of herbal origin for the mitigation of deleterious effects of environmental pollutants like ionizing radiation, mainly to protect against radiation leakages resulting from mishaps in nuclear reactors, deliberate use of dirty bombs, etc. METHOD: The radio modifying effects of a fractionated extract of the high-altitude Himalayan plant species Rhodiola imbricata, along with its electron-donation potential, super-oxide ion scavenging (IC50 ≤ 0.025 mg/ml), nitric oxide (NO) scavenging potential (IC(50) = 0.5 mg/ml), and antihemolytic activity were evaluated in the present study. Reducing power, superoxide ion (O(2)(•-)), and nitric oxide scavenging ability of the fractionated extract increased in a dose-dependent manner. Rhodiola imbricata also exhibited antihemolytic potential preventing radiation-induced membrane degeneration of human erythrocytes. CONCLUSION: Thus, it can be stated that Rhodiola imbricata provides protection against gamma radiation via multifarious mechanisms that act in a synergistic manner. Rhodiola imbricata is widely used as a nutraceutical supplement in the trans-Himalayan region nations, and the current study shows that Rhodiola has immense potential for alleviation of biological damage in a radiation environment.

Neuroprotection of the nigrostriatal dopaminergic neurons by melatonin in hemiparkinsonium rat.

BACKGROUND & OBJECTIVES: Several lines of evidence point to a significant role of antioxidants in Parkinson's disease (PD). Few studies report that melatonin, a neurohormone, is one of the best physiological antioxidants. Review of literature indicates that none of the drugs so far studied for preventing the PD was found to be promising for use. Therefore in the present study the effect of neuroprotectory melatonin was tested against 6-hydroxydopamine (6-OHDA) neurotoxicity for striatal dopaminergic neurons in the rat. METHODS: Thirty animals were randomly divided into two groups. Animals of group 1 received saline (melatonin vehicle) daily 1 ml ip for seven days. Melatonin (500 mug/kg body weight dissolved in 1 ml saline ip) was administered in rats of group 2 for seven days. Then all animals of groups 1 and 2 were lesioned unilaterally with 8 mug 6-OHDA into the lateral striatum on 8(th) day. Various behaviour and histological tests were used to evaluate the neuroprotective effect of melatonin. RESULTS: Statistically significant difference in various behaviour tests was found between post lesion values of group 1 and group 2 (P<0.001 in apomorphine-induced rotational behaviour, staircase test (success rate), disengage time and P<0.05 in stepping test, initiation time, postural balance test). INTERPRETATION & CONCLUSION: Our results demonstrated that melatonin acted as an effective neuroprotective agent for striatal dopaminergic neurons in 6-OHDA lesioned rat model of Parkinson's disease.

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans.

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

Radioprotection by a herbal preparation of Hippophae rhamnoides, RH-3, against whole body lethal irradiation in mice.

PURPOSE: Hippophae rhamnoides L. has been well documented to have anti-oxidative, immunostimulative and regenerative properties and therefore a herbal preparation of H. rhamnoides coded as RH-3 was investigated for its radioprotective action. MATERIALS AND METHODS: RH-3 was administered intraperitonially (i.p.) to mice 30 minutes before whole body irradiation and whole body survival, spleen Colony forming units (CFU) and haematological parameters were studied. To investigate free radical scavenging and antioxidant potential, Fenton reaction, radiation mediated OH radical scavenging and chemically generated superoxide anions scavenging were studied in vitro while inhibition of lipid peroxidation was studied in liver homogenate of mice. RESULTS: A dose of 30 mg/kg body weight of RH-3 rendered 82% survival as compared to no survival in irradiated control. The endogenous CFU counts in mouse spleen on 10th post-irradiation day with and without RH-3 demonstrated radioprotective effect. Various hematological parameters also corroborated the radioprotective effect of RH-3. In a dose dependent manner, RH-3 inhibited Fenton reaction and radiation mediated generation of hydroxyl radicals in vitro, superoxide anion mediated Nitroblue tetrazolium (NBT) reduction and FeSO4 mediated lipid peroxidation in liver. CONCLUSION: Free radical scavenging, acceleration of stem cell proliferation and immunostimulation are the radioprotective attributes, which require further investigations.