IRL-1620, an endothelin-B receptor agonist, enhanced radiation induced reduction in tumor volume in Dalton's Lymphoma Ascites tumor model.

ETB receptor agonist, IRL-1620 (or SPI-1620) presently in US Phase 1 clinical trial, has been demonstrated to selectively and transiently increase tumor blood flow. The present study was conducted to determine the effect of IRL-1620 on radiation therapy in tumor bearing mice inoculated with Dalton's Lymphoma Ascites cells. Tumors were allowed to grow for 30 days to a size of 1.10-1.29 cm3 before starting the treatment. The animals with or without IRL-1620 treatment were exposed to radiation (4 Gy/dose) on every alternate day for a total of 5 doses. Tumor volume was determined twice every week till the end of study. Radiation alone did not affect the tumor volume; however, animals treated with IRL-1620 followed by radiation produced a significant (64%) reduction in tumor volume. Survival of mice improved from 0/10 at 56 days after tumor inoculation in vehicle plus radiation group to 6/10 at 70 days in IRL-1620 (9 nmol/kg) plus radiation group. It is concluded that IRL-1620 improves the efficacy of radiation treatment in tumor bearing mice. (These findings have been earlier presented as an abstract ).

Andrographis paniculata downregulates proinflammatory cytokine production and augments cell mediated immune response in metastatic tumor-bearing mice.

Effects of Andrographis paniculata extract and its major component, andrographolide, on cell-mediated immune responses in metastatic tumor bearing animals were studied. NK cell mediated target cell lysis was enhanced by the administration of Andrographis paniculata extract (45.0% cell lysis) and andrographolide (40.2% cell lysis) on the 5th day after tumor induction when compared to untreated metastatic tumor bearing animals in which maximum target cell lysis was observed on 11th day (11.4%). Antibody dependent cell-mediated cytotoxicity (ADCC) was also enhanced by treatment with the extract (42.0% cell lysis) and andrographolide (40.2%) in comparison with the untreated case (11.0%). Similarly, the extract (25%) and andrographolide (22%) showed higher ACC activity than the control (14%) and treatment of extract and andrographolide resulted in significant increase in serum IL-2 and TIMP-1 levels. Furthermore, the levels of proinflammatory cytokines such as IL-1ß, IL-6, GM-CSF and TNF-α were effectively reduced by the administration of extract and andrographolide in metastatic tumor bearing animals.

Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by Abrin.

The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.

Effect of naturally occurring triterpenoids ursolic acid and glycyrrhizic acid on the cell-mediated immune responses of metastatic tumor-bearing animals.

Effect of terpenoids, ursolic acid and glycyrrhizic acid on the cell-mediated immune response was studied in metastatic tumor-bearing C57BL/6 mice. Intraperitoneal administration of ursolic acid and glycyrrhizic acid (50 mumoles/Kg body wt for 5 consecutive days) was found to produce increased natural killer cell activity (NK-activity) in metastatic tumor-bearing animals. In the glycyrrhizic acid- and ursolic acid-treated groups the peak activity was observed on the 4(th) day (60.2% and 43% cell lysis respectively). Whereas in control animals the maximum cell lysis was obtained only on 16(th) day (25% cell lysis). Administration of terpenoids clearly enhanced the antibody dependent cell mediated cytotoxicity (ADCC). In tumor-bearing control animals maximum cell lysis was obtained only on the 16(th) day (20% cell lysis). But in the case of glycyrrhizic acid- and ursolic acid-treated groups, the maximum lysis was obtained on the 12(th) day. and it was 47% and 32.5% cell lysis, respectively. Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 +/- 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).

Inhibition of tumor specific angiogenesis by amentoflavone.

The formation of new capillaries from existing blood vessels is critical for tumor growth and metastasis. In this study we report that amentoflavone, a biflavonoid from Biophytum sensitivum, could inhibit the process of angiogenesis. Amentoflavone at nontoxic concentrations (0.05-0.2 microg/ml) showed significant inhibition in the proliferation, migration, and tube formation of endothelial cells, which are key events in the process of angiogenesis. In vivo studies in C57BL/6 mice using amentoflavone showed remarkable inhibition (52.9%) of tumor directed capillary formation. Amentoflavone showed inhibitory effect on the production of various endogenous factors such as IL-1beta, IL-6, TNF-alpha, GM-CSF, and VEGF that control the process of angiogenesis. Amentoflavone treatment could increase the production of IL-2 and TIMP-1, which could successfully shift the equilibrium towards an angiostatic condition. The antiangiogenic activity of amentoflavone was supported by its remarkable suppression in sprouting of microvessels from rat aorta. Our results also show that amentoflavone could inhibit the production of VEGF mRNA in B16-F10 cells. These findings indicate that amentoflavone inhibits angiogenesis by disrupting the integrity of endothelial cells and by altering the endogenous factors that are required for the process of neovascularization.

Effect of Andrographis paniculata as an adjuvant in combined chemo-radio and whole body hyperthermia treatment - a preliminary study.

Modulation of immune responses to alleviate disease has been of interest for a long time. Intraperitoneal administration of Andrographis paniculata extract along with whole body hyperthermia (WBH) was found to enhance the total WBC count in cyclophosphamide (CTX) and radiation treated animals when compared to untreated control animals. Maximum inhibition in the solid tumor development was observed when the CTX and radiation exposed animals were treated with extract in combination with whole-body hyperthermia. Similarly myeloperoxidase activity in tumor tissue from CTX and radiation-treated animals was also significantly inhibited when they were administered with Andrographis paniculata extract along with whole body hyperthermia. Moreover the production of cytokines such as IL-2 and GM-CSF, which was reduced after combined CTX and radiation treatment was significantly increased by the simultaneous treatment of extract and whole body hyperthermia. The elevated level of serum Tumor Necrosis Factor (TNF-alpha) level, after CTX and radiation treatment was also lowered significantly after the administration of extract and simultaneous exposure of whole-body hyperthermia with respect to untreated tumor-bearing animals.

Effect of Biophytum sensitivum on cell-mediated immune response in mice.

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.

Modulation of cell-mediated immune response in B16F-10 melanoma-induced metastatic tumor-bearing C57BL/6 mice by sulforaphane.

Effect of sulforaphane on cell-mediated immune response (CMI) was studied in B16F-10 melanoma-induced metastasis-bearing C57BL/6 mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in metastatic tumor-bearing animals (43.17% cell lysis, on day 5) and the activity was observed earlier than in tumor-bearing control animals (maximum of 9.76% cell lysis, on day 9). Antibody-dependent cellular cytotoxicity also was enhanced significantly in metastatic tumor-bearing animals (41.20% cell lysis on day 9) after sulforaphane administration compared with untreated control tumor-bearing animals (maximum of 12.62% cell lysis on day 15). An early antibody-dependent complement-mediated cytotoxicity also was observed in sulforaphane-treated tumor-bearing animals (26% cell lysis, on day 15). Administration of sulforaphane significantly enhanced the production of IL-2 and IFN-gamma in metastatic tumor-bearing animals. In addition, sulforaphane significantly downregulated the serum levels of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and GM-CSF during metastasis. These data clearly suggest that sulforaphane effectively inhibited the spread of metastatic tumor cells through the stimulation of CMI, upregulation of IL-2 and IFN-gamma, and downregulation of proinflammatory cytokines IL-1beta, IL-6, TNF-alpha, and GM-CSF.

Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide.

The stimulatory effect of Andrographis paniculata extract and andrographolide on cytotoxic T lymphocyte (CTL) production was determined in BALB/c mice by Winn's neutralization assay using CTL sensitive EL4 thymoma cells as target cell. Extract and andrographolide showed a significant increase in CTL production in both the in vivo and in vitro models. The survival time of EL4 cells alone in animals was only 27.1 days and it was increased to 51.1 and 44.5 days in extract- and andrographolide treated animals with percentage increase in life span (%ILS) of 88.5 and 64.2, respectively. The survival rate of animals administered EL4 cells incubated with alloimmunized spleen cells (effector cells) from normal BALB/c mice was 35.8 (%ILS 32.1). When this group was treated with 10 doses of extract and andrographolide the life span was further increased to 52.1 days (%ILS 92.2 ) and 48.1 days (%ILS 77.4). Survival days of animal carrying EL4 cells incubated with alloimmunized spleen cells (effector cells) from extract and andrographolide treated animals were 55.5 and 50.3 days respectively. When these animals continued with extract and andrographolide treatment for 10 days their life spans were significantly increased to 62 and 53.8 days, respectively. The level of cytokines such as Interlevkin (IL)-2 and Interferon (IFN)-gamma also was enhanced in these animals when they were treated with extract and andrographolide. This study demonstrated that A. paniculata extract and andrographolide stimulate the CTL production through enhanced secretion of IL-2 and IFN-gamma by T cells and thereby inhibit the tumor growth.

Modulation of natural killer cell activity, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by andrographolide in normal and Ehrlich ascites carcinoma-bearing mice.

Modulation of immune responses is highly relevant in tumor cell destruction. The present study is focused on the effect of Andrographis paniculata extract (APE) and its isolated compound andrographolide (ANDLE) on cell-mediated immune responses in normal and tumor-bearing control animals. Treatment with APE and ANDLE significantly enhanced natural killer cell activity in normal (APE, 46.82% cell lysis; ANDLE, 40.79% cell lysis) and tumor-bearing animals (APE, 48.66% cell lysis; ANDLE, 42.19% cell lysis) on the fifth day, and it was observed earlier than in tumor-bearing control animals (12.89% cell lysis on day 9). Antibody-dependent cellular cytotoxicity was also increased in APE (45.17% cell lysis on day 11) as well as ANDLE (39.92% cell lysis on day 11)-treated normal and tumor-bearing animals (APE, 47.39% cell lysis; ANDLE, 41.48% cell lysis on day 11) compared to untreated tumor-bearing control animals (maximum of 11.76% cell lysis on day 17). An early enhancement of antibody-dependent complement-mediated cytotoxicity was also observed by the administration of APE and ANDLE in normal as well as tumor-bearing animals. APE and ANDLE administration could significantly enhance the mitogen-induced proliferation of splenocyte, thymocyte, and bone marrow cells. Moreover, treatment of APE and ANDLE significantly elevated the production of interleukin-2 and interferon-gamma in normal and Ehrlich ascites carcinoma-bearing animals.

Immunomodulatory activity of Sulforaphane, a naturally occurring isothiocyanate from broccoli (Brassica oleracea).

The effect of Sulforaphane on the immune system was studied using BALB/c mice. Intraperitoneal administration of five doses of Sulforaphane (500 microg/dose/animal/day) was found to enhance the total WBC count (12,950 cells/mm3) on 9th day. Bone marrow cellularity (23 x 10(6) cells/femur) and number of alpha-esterase positive cells (1346.66/4000 cells) were also increased by the administration of Sulforaphane. Treatment with Sulforaphane along with the antigen, sheep red blood cells (SRBC), produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (315.83 PFC/10(6) spleen cells) was obtained on the 6th day. Administration of Sulforaphane also showed an enhancement in the phagocytic activity of peritoneal macrophages. Moreover administration of Sulforaphane significantly reduced the elevated level of TNF-alpha production by LPS stimulated macrophages. These results indicate the immunomodulatory activity of Sulforaphane.

Antiangiogenic activity of Andrographis paniculata extract and andrographolide.

Inhibition of angiogenesis is currently perceived as one of the promising strategies in the treatment of cancer. In this study we analyzed the antiangiogenic activity of Andrographis paniculata extract (APE) and its major component andrographolide (ANDLE) using both in vitro and in vivo models. Intraperitoneal administration of APE and ANDLE significantly inhibited the B16F-10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis of serum cytokine profile showed a drastic elevation in the proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in B16F-10 cell line showed a reduced level of expression in the presence of APE and ANDLE. Serum NO level which was increased in B16F-10 melanoma injected control animals was also found to be significantly lowered by the administration of APE and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was elevated in APE and ANDLE treated angiogenesis induced animals. In the rat aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic concentrations. Taken together our results demonstrate that APE and ANDLE inhibit the tumor specific angiogenesis by regulating the production of various pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide, VEGF, IL-2 and TIMP-1.

Augmentation of natural killer cell and antibody-dependent cellular cytotoxicity in BALB/c mice by sulforaphane, a naturally occurring isothiocyanate from broccoli through enhanced production of cytokines IL-2 and IFN-gamma.

Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-gamma in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.

A preliminary study on antimetastatic activity of Thuja occidentalis L. in mice model.

The effect of Thuja occidentalis extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. The extract was administered by three different modalities. A remarkable reduction in tumor-nodule formation was shown by simultaneous (74.4%) and prophylactic (71.5%) mode of administration. The effect was comparatively low in drug administration after tumor development (60.2%). Increased lung collagen hydroxyproline (21.13 microg/mg protein) in the metastasized lungs of control animals compared with normal animals (0.98 microg/mg protein) was significantly reduced in Thuja-treated animals. The elevated level of uronic acid (349.5 microg/100 mg tissue) and hexosamine contents in metastatic control animals was significantly reduced in the animals treated with alcoholic extract of Thuja. Similarly the elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with the extract of Thuja. The lifespan of the Thuja treated animals also was seen to be significantly increased.

Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees.

In this study, we explored the antioxidant and anti-inflammatory properties of the medicinal herb Andrographis paniculata using in vitro as well as in vivo systems. Methanolic extract of Andrographis paniculata was found to inhibit formation of oxygen derived free radicals such as superoxide (32%) hydroxyl radicals (80%) lipid peroxidation (80%) and nitric oxide (42.8%) in in vitro system. In vivo studies using BALB/c mice models also showed significant inhibition in PMA induced superoxide (32.4%) and nitric oxide (65.3%) formation. Interestingly we also found that, administration of Andrographis paniculata extract produced complete inhibition of carageenan induced inflammation compared with control models.

Piper longum inhibits VEGF and proinflammatory cytokines and tumor-induced angiogenesis in C57BL/6 mice.

The antiangiogenic activity of Piper longum was studied using in vivo as well as in vitro models. In vivo, antiangiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. Intraperitoneal administration of the extract (10 mg/dose/animal) significantly inhibited (50.6%) the number of tumor-directed capillaries induced by injecting B16F-10 melanoma cells on the ventral side of C57BL/6 mice. The cytokine profile in the serum of these animals showed a drastically increased level of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, GM-CSF and the direct endothelial cell proliferating agent, VEGF. Administration of the methanolic extract of P. longum could differentially regulate the level of these cytokines. The level of IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) was increased significantly when the angiogenesis-induced animals were treated with the extract. The extract of P. longum at non-toxic concentrations (10 microg/ml, 5 microg/ml, 1 microg/ml) inhibited the VEGF-induced vessel sprouting in rat aortic ring assay. Moreover, P. longum was able to inhibit the VEGF-induced proliferation, cell migration and capillary-like tube formation of primary cultured human endothelial cells. Hence, the observed antiangiogenic activity of the plant P. longum is related to the regulation of these cytokines and growth factors in angiogenesis-induced animals.

Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice.

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack of tumor specificity. Immunological and biochemical studies were here carried out to investigate protective effects of ethanolic extract of Andrographis paniculata against cyclophosphamide (CTX) induced toxicity in vivo. Intraperitoneal administration of the extract significantly increased the total WBC account (3256.5+/-196 cells/cm(2)), bone marrow cellularity (17.1+/-10.4x10(6) cells/femur) and betaesterase positive cells (849+/-23.2 cells/4000 cells) in CTX treated animals, when compared to CTX alone treated control mice. Weights of lymphoid organs such as a spleen and thymus, reduced by CTX administration, were also increased by A paniculata treatment. Reduction of GSH in liver (4.8+/-0.21nmol/mg protein) and in intestinal mucosa (13+/-0.67 nmol/mg protein) of CTX-treated controls was significantly reversed by A paniculata administration (liver: 6.4+/-0.13, intestinal mucosa: 17.11+/-0.06), with amelioration of changes in serum and liver ALP, GPT, LPO (lipid peroxidation). Histopathological analysis of small intestine also suggests that extract could reduce the CTX induced intestinal damage. The level of proinflammatory cytokine TNF-alpha, which was elevated during CTX administration, was significantly reduced by the A paniculata extract administration. The lowered levels of other cytokines like IFN-gamma, IL-2, GM-CSF, after CTX treatment were also found to be increased by extract administration.

Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor angiogenesis and malignancies.

Angiogenesis is a process by which new blood vessels are formed from preexisting vessels. New blood vessel formation by angiogenesis involves the degradation of extra-cellular matrix combined with sprouting and migration of endothelial cells from preexisting capillaries. Solid tumors consist of several components, including normal and stromal cells, extracellular matrix, and vasculature. To grow and metastasize, tumors must stimulate the development of new vasculature through angiogenesis. Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine regeneration. VEGF is both a vascular growth factor and a vascular permeability factor. Its expression can upregulate several proangiogenic and prometa-static molecules. As a central mediator of angiogenesis, VEGF has emerged as an important target for antiangiogenic therapy. In this review, the authors describe the essential characteristics of VEGF and the VEGF family of ligands and their receptors. They also provide an overview of the central role of VEGF in physiologic and pathologic angiogenesis, directly or indirectly. This review sheds light on the importance of VEGF-targeted antiangiogenic therapy based on the monoclonal antibodies against VEGF, small interfering RNA, and therapy directed against VEGF-VEGFR kinase. It also gives a brief overview of the natural products or dietary compounds that could be used as antiangiogenic agents. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk or of micrometastases after surgical removal of primary tumor.

Protective effect of Thuja occidentalis against radiation-induced toxicity in mice.

The effect of Thuja occidentalis against damage induced by gamma radiation was studied. Whole-body exposure of Swiss albino mice to gamma-rays (6 Gy) reduced the total white blood cell count to 1900 cells/mm(3) on the third day, which was elevated to 2050 cells/mm(3) by the administration of alcoholic extract ofT occidentalis (5 mg/dose/animal, intraperitoneally). Six animals from each group were killed after 2, 7, and 11 days of irradiation to detect the bone marrow cellularity and radiation-induced toxicity. The number of bone marrow cells and alpha-esterase positive cells in control animals after 11 days was reduced to 12.2 x 10(6) cells/femur and 693.5/4000 cells, respectively. In T occidentalis-treated animals, bone marrow cellularity was increased to 16.9 x 10(6) cells/femur and alpha-esterase positive cells were 940/4000 cells, a nearly normal level. Alcoholic extract of T occidentalis reduced the elevated levels of GPT and alkaline phosphatase in liver and serum after irradiation. The lipid peroxidation levels were also lowered in the irradiated animals treated with the Thuja extract.

Protective effect of Piper longum fruit ethanolic extract on radiation induced damages in mice: a preliminary study.

The radioprotective property of an ethanolic extract of Piper longum fruits (EEPLF) was investigated in Swiss mice. The white blood cell (WBC) count in irradiated control mice was drastically reduced to 1900 cells/mm3 on third day but in treated animals the count was 2783.3 cells/mm3. The number of bone marrow cells and alpha-esterase positive cells was also enhanced by the EEPLF administration (16.7 x 10(6) cells/femur and 946.5/4000 cells, respectively) when compared to the radiation exposed control animals (12.2 x 10(6) cells/femur and 693.5/4000 cells, respectively). EEPLF reduced the elevated levels of glutathione pyruvate transaminase (GPT), alkaline phosphatase (ALP), and lipid peroxidation (LPO) in liver and serum of radiation treated animals. The extract administration also increased the reduced glutathione (GSH) production to offer the radioprotection.