Effect of Tussilago farfara L. Polysaccharides on the Content of Hematopoietic Stem Cells (CD117+34+) in the Bone Marrow of Mice Treated with Cyclophosphamide.

Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117+34+) in the bone marrow.

Fermented Red Ginseng Alleviates Cyclophosphamide-Induced Immunosuppression and 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Regulating Macrophage Activation and T Cell Differentiation.

A variety of products have been developed with red ginseng (RG, the steamed roots of Panax ginseng Meyer). To clarify the immunomodulating effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), enzyme-treated eRG (ERG) and probiotic-fermented eRG (FRG), we examined their immunopotentiating and immunosuppressive effects in mice with cyclophosphamide (CP)-induced immunosuppression (CI) or 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis (TC). Oral administration of RG in CI mice significantly increased blood IFN- γ levels. Treatment with RG also increased the tumoricidal effects of CI mouse splenic cytotoxic T (Tc) and NK cells against YAC-1 cells. Treatment with RGs, in particular FRG and wRG, significantly increased Th1 cell differentiation. Treatment with RG except wRG increased Treg cell differentiation. However, wRG alone increased IL-6 and IL-17 expression in the colon of CI mice. Furthermore, RG alleviated colitis in TC mice. FRG most potently suppressed TNBS-induced colon shortening, NF- κ B activation and TNF- α and IL-17 expression and increased IL-10 expression. RGs inhibited TNF- α expression and increased IL-10 expression in lipopolysaccharide-stimulated primary macrophages in vitro while the differentiation of splenic T cells into type 1 T (Th1) and regulatory T (Treg) cells was increased by FRG in vitro. In conclusion, FRG can alleviate immunosuppression and inflammation by inhibiting macrophage activation and regulating Th1 and Treg cell differentiation.

Antigenotoxicity protection of Carapa guianensis oil against mitomycin C and cyclophosphamide in mouse bone marrow.

The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct- and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct- and indirect-acting chemical mutagens, in a mammalian model.

Effects of Astragalus Combined with Angelica on Bone Marrow Hematopoiesis Suppression Induced by Cyclophosphamide in Mice.

Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g·kg-1), Angelica (3.00 g·kg-1), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g·kg-1+Angelica 0.98 g·kg-1), 5 : 1 (Astragalus 9.00 g·kg-1+Angelica 1.80 g·kg-1), 2 : 1 (Astragalus 7.71 g·kg-1+Angelica 3.08 g·kg-1), 1 : 1 (Astragalus 5.40 g·kg-1+Angelica 5.40 g·kg-1), 1 : 2.5 (Astragalus 3.08 g·kg-1+Angelica 7.71 g·kg-1), 1 : 5 (Astragalus 1.80 g·kg-1+Angelica 9.00 g·kg-1), and 1 : 10 (Astragalus 0.98 g·kg-1+Angelica 9.81 g·kg-1). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).

Cardioprotective Effect of Selenium Against Cyclophosphamide-Induced Cardiotoxicity in Rats.

The objective of this study is to evaluate the possible protective effects of selenium (Se) against cyclophosphamide (CP)-induced acute cardiotoxicity in rats. A total of 42 male Spraque-Dawley rats were divided into six groups (n = 7). Rats in the first group were served as control. Rats in the second group received CP (150 mg/kg) at the sixth day of experiment. Animals in the third and fourth groups were treated with only 0.5 and 1 mg/kg Se respectively for six consecutive days. Rats in the fifth and sixth groups received respective Se doses (0.5 or 1 mg/kg) for 6 days and then a single dose of CP administered on the sixth day. On day 7, the animals were sacrificed; blood samples were collected to measure malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and ischemia-modified albumin (IMA) levels. Heart tissues were processed routinely and tissue sections were stained with H + E for light microscopic examination. In the CP-treated rats MDA, LDH, CK-MB, and IMA serum levels increased, while GSH levels decreased. Microscopic evaluation showed that tissue damage was conspicuously lower in CP plus Se groups. Moreover, 1 mg/kg Se was more protective than 0.5 mg/kg Se as indicated by histopathological and biochemical values. In conclusion, Se is suggested to be a potential candidate to ameliorate CP-induced cardiotoxicity which may be related to its antioxidant activity.

Antigenotoxicity protection of Carapa guianensis oil against mitomycin C and cyclophosphamide in mouse bone marrow

ABSTRACT The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct- and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct- and indirect-acting chemical mutagens, in a mammalian model.

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties.

Phytotrapy of cyclophosphamide-induced immunosuppression.

Cyclophosphamide (CP) is a cytotoxic drug that can suppress both humoral and cellular immunity. Combining traditional medicinal herbs and chemotherapy drugs are used to improve immunity and quality of life performance status. In this paper, the effects of plant extracts, active components and their derivatives on immunosuppression of CP are discussed. Appropriate keywords were used to search through PubMed, Google Scholar, and Sciverse. All relevant results published from 1990 to date were chosen for final review. Over 50 references were found in which plant extracts, active components and their derivatives have been tested for their immune protective effects against CP-induced immune toxicity. Although there are several plants shown to be effective in animal models, no study was carried out on human subjects. According to the results; we can claim that plants and their active ingredients are good candidates for alternative adjuvant chemotherapy in reducing the immunotoxicity of CP.

Cuscuta chinensis Ameliorates Immunosuppression and Urotoxic Effect of Cyclophosphamide by Regulating Cytokines - GM-CSF and TNF-Alpha.

Cancer is the leading cause of death worldwide. Cyclophosphamide (CTX) is commonly used as anticancer drug which causes toxicity by its reactive metabolites such as acroline and phosphoramide mustard. In this study, Cuscuta chinensis (C. chinensis) (family: Convolvulaceae) was assessed for ability to restore mice against CTX-induced toxicity. Coadministration of C. chinensis extract (10 mg/kg BW, IP, daily) for ten consecutive days reduced CTX-induced (25 mg/kg BW, IP, daily) toxicity. Treatment with C. chinensis extract significantly (p < 0.01) increased the relative organ weight and body weight. Moreover, administration of C. chinensis extract significantly increased bone marrow cellulatity and α-esterase activity in CTX-treated mice which suggested its protective role on the hematopoietic system. The GSH content was drastically reduced by CTX administration in urinary bladder which was enhanced by treatment with C. chinensis extract, indicating that preventing acroline-mediated tissue damage or cell toxicity and also the extract decreased the urinary bladder nitric oxide (NO) level which proves recovery over urinary tract injury associated with CTX treatment. The administration of C. chinensis extract decreased serum urea, creatinine, and bilirubin levels when compared to CTX-alone-treated group. Histopathological analysis of the urinary bladder of CTX-alone-treated group showed necrotic damage whereas the C. chinensis-treated group showed normal bladder architecture. The above data clearly demonstrates chemoprotective role of C. chinensis against CTX-induced toxicities by regulating antioxidant and inflammatory mediators.

Blueberry anthocyanins-enriched extracts attenuate the cyclophosphamide-induced lung toxicity.

The influence of blueberry anthocyanins-enriched extracts (BAE) on cyclophosphamide (CTX)-induced lung damage was investigated. BAE (20 and 80mg/kg/d) were orally dosed to rats 7d both before and after CTX administration (100mg/kg, intraperitoneal injection, single dose). The results showed CTX treatment induced obvious pathological pulmonary injury with raised injury score and lung/body weight ratio. In CTX group, the activity of lysosomal proteases, lung permeability and the number of neutrophil infiltrates all elevated. On the other hand, claudin-4 and zonula occluden-1 protein levels decreased. And also changes of oxidative stress and inflammatory cytokines parameters together with nuclear factor-κB activation were shown. Improvement of all above-mentioned physiological and biochemical parameters was exhibited in BAE groups, with a dose-dependent manner. In conclusion, BAE attenuate the CTX-induced lung toxicity, antioxidant and anti-inflammatory characteristics are involved in the protective mechanism of BAE.

Synergestic effect of lycopene and melatonin against the genesis of oxidative stress induced by cyclophosphamide in rats.

Cyclophosphamide (CP) is an alkylating agent that has been considered effective for cancer treatment. Lycopene, the pigment in tomato fruits, has beneficial effect in the treatment of some diseases. The goal of this study is to evaluate the protective effect of lycopene alone or combined with melatonin (Mel) in inhibiting the oxidative stress and toxic effect of CP in rats. Five groups of rats were included in this study; Group I served as the control. Rats in groups II-V were administrated with single dose of CP (150 mg/kg B.W) interperitoneally for 3 days. On the same day of CP administration, the rats in group III were fed a diet supplemented with lycopene (50 mg/kg of diet), rats in group IV were administered with a dose of 2.5 mg Mel/kg body weight (bw) injected subcutaneously and rats in group V were supplemented with lycopene and a dose of 2.5 mg Mel/kg bw injected subcutaneously. After 15 days the blood samples were collected. Results obtained showed that CP exerted its toxic effect by increasing the free radicals and reactive oxygen species that causes lipid peroxidation and cell damage, and this in turn is detected by elevation in nitric oxide (NO) and malondialdehyde (MDA), while the activities of antioxidants enzymes including (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) were significantly decreased as compared with the control rats. The combined treatment (Lyco + Mel) group showed potential reduction in these parameters more than those treated with lyco alone. The activities of SOD, CAT and GPx were found significantly high than lyco alone treated rats. A positive significant correlation between NO and MDA (r = .81). In conclusion, these results suggested that supplementation of diet with lycopene and Mel provided antioxidant defense with strong chemopreventive activity against Cp-induced cytotoxicity.

Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs that show a high therapeutic index, despite the widespread side effects and toxicity particularly in high-dose regimens and long-term use. Here, we evaluated and compared the efficacy of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) in alleviating the genotoxicity, immunosuppression and other complications induced by CP in non-tumour-bearing albino rats. The present study showed (probably for the first time) that both MLP and MLE significantly alleviated (P < 0·05-0·001) most side effects and toxicity of CP-treated rats including the increase in chromosomal aberrations of bone marrow cells and serum malondialdehyde level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells. The modulatory effects of marjoram leaves shown in the present study were dose dependent in most cases and much higher in MLE (21-23 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, sweet marjoram leaves (especially in the form of a herbal tea) may be useful as an immunostimulant and in reducing genotoxicity in patients under chemotherapeutic interventions.

Immunostimulatory effects of Uncaria perrottetii (A. Rich.) Merr. (Rubiaceae) vinebark aqueous extract in Balb/C mice.

AIMS OF THE STUDY: Crude extract of Uncaria perrottetii (A. Rich.) Merr. vinebark was evaluated for its immunomodulating activity in Balb/C mice. Initially, the immunomodulatory potential of the plant extract was evaluated using in vitro immune response assays at different concentrations of the plant extract (10 µg/mL, 20 µg/mL, 50 µg/mL and 100 µg/mL). Using the optimum concentration determined in the in vitro assays, the protective effect of the plant extract was assessed against drug-induced immunosuppression in vivo. MATERIALS AND METHODS: For the in vivo experiment, thirty-six (36) mice were divided into 3 groups of 12 mice each: (1) cyclophosphamide drug-induced (30 mg/kg BW) immunosuppressed mice (Cy group) served as the positive control; (2) Uncaria perrottetii extract and Cy-treated mice (U+Cy); and (3) PBS-injected mice as the negative control group [(-) CTRL]. RESULTS: The optimum concentration was determined to be 50 µg/mL in the in vitro assays. At this concentration, Uncaria perrottetii extract stimulated peritoneal phagocyte activation, produced a significant increase in the activity of phagocytic cells from the spleen and promoted splenic cellular proliferation with or without lipopolysaccharide (LPS) when compared with the PBS-treated cells (negative control). Moreover, cells treated with 50 µg/mL of Uncaria perrottetii increased macrophage respiratory burst activity that was comparable to that of the phorbol myristate acetate-stimulated splenic macrophages. In all immune assays undertaken in the in vivo experiment, the Cy-treated mice showed significantly lower response when compared with the PBS-treated mice. Significant improvement in peritoneal cell activation, phagocytic activity and cellular proliferation was exhibited by the U+Cy-treated mice when compared with Cy-injected mice. The extract from Uncaria perrottetii also significantly enhanced respiratory burst and plasma lysozyme activity compared with the Cy-injected mice. CONCLUSIONS: Based on the results of both in vitro and in vivo trials, Uncaria perrottetii extract has immunopotentiating activities on the innate immunity of Balb/C mice and the extract could potentially reverse the immunosuppressive effects of Cy. However, the potential of the plant as source of bioactive products and metabolites for drug development still has to be fully investigated.

Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats.

This study examined the possible protective effects of thymoquinone (TQ), the main constituent of the volatile oil of black seed (Nigella sativa), against cyclophosphamide (CP)-induced cardiotoxicity. Adult male Wistar albino rats were divided into four treatment groups. Rats in the first group were served as control. Rats in the second group received TQ (50 mg/L in drinking water) for 12 days. Animals in the third group were injected with a single dose of CP (200 mg/kg, IP) at day 5. Rats in the fourth group received TQ (50 mg/L in drinking water) for 5 days before a single dose of CP (200 mg/kg, IP) and continued thereafter throughout the experiment. On day 13, animals were sacrificed; serum and hearts were isolated and analyzed. Cyclophosphamide resulted in a significant increase in serum creatine kinase, lactate dehydrogenase, cholesterol, triglycerides, creatinine, urea, and tumor necrosis factor-α. In heart tissues, CP resulted in a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione, glutathione peroxidase, catalase, and adenosine triphosphate levels. Interestingly, TQ supplementation resulted in a complete reversal of all the biochemical changes induced by CP to their control values. Data from this study suggest that TQ supplementation attenuates CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to decrease oxidative and nitrosative stress and to preserve the activity of antioxidant enzymes as well as its ability to improve the mitochondrial function and energy production. .

Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide.

Constituents of the Nigella sativa seed are reported to possess potent antioxidant effects. Treatment with anticancer drugs such as cyclophosphamide (CTX) is associated with significant toxicity due to over-production of reactive oxygen species, resulting in increased levels of oxidative stress. The aim of this study is to test whether or not N. sativa L oil (NSO) or its active ingredient, thymoquinone (TQ), can reduce CTX-induced toxicity. Male albino rats were treated with intraperitoneal administration of phosphate buffered saline (PBS) or 200 mg/Kg CTX followed by intragastric administration of NSO or TQ on alternate days for 12 days. Administration of NSO and TQ was initiated 6 h before or after CTX injection. Twenty-four hours after the last NSO and TQ treatment, blood and liver were harvested to analyse toxicity-related parameters. Treatment with CTX induced significant toxicity as shown by decrease in haemoglobin concentration and increases in blood sugar levels, activities of liver enzymes, bilirubin, urea, creatinine, lipids (triglyceride, cholesterol and low-density lipoprotein (LDL)-cholesterol) and lipid peroxidation in the liver. Treatment with NSO or TQ induced significant reduction in overall toxicity. The antitoxic effects of NSO and TQ were associated with induction of antioxidant mechanisms. These results suggest that administration of NSO or TQ can lower CTX-induced toxicity as shown by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimise the toxic effects of treatment with anticancer drugs.

Folic acid and soybean isoflavone combined supplementation protects the post-neural tube closure defects of rodents induced by cyclophosphamide in vivo and in vitro.

To evaluate the neuroprotective effect of folic acid (FA) and soybean isoflavone (SIF) combined supplementation on the post-neural tube closure of rodents induced by cyclophosphamide (CPA) in vitro and in vivo, pregnant rats were randomly divided into control, model, solo-FA intervention, solo-SIF intervention and co-intervention of FA and SIF groups. Rats in solo-intervention groups and co-intervention group were treated with FA 0.7 mg/kg, SIF 160 mg/kg and FA 0.7 mg/kg+SIF 160 mg/kg at the duration of pregnancy, respectively. On the 13th day of gestation, control rats were given physiological saline and the other four groups were treated with CPA12.5mg/kg. On the 14th day of gestation, three rats selected randomly from every group were executed and the ultrastructure, DNA damage and the proteins expressions of Bcl-2, Bax and P53 on embryo brains were checked. The rest of the rats were executed on the 20th day, the frequency of neural tube closure defects and fetus' development indices were measured. In addition, T-SOD, MDA and NO in serum of the pregnant rats were checked. In vitro, the effect of FA and genistein on the apoptosis was determined. Compared with the model group, the malformation incidence was lower but fetus' development indices were higher in the combination treated group. The combination decreased the damage of CPA, such as damaged nuclear DNA, early apoptotic morphological changes, Bax and P53 expressions on embryo brains and in vivo. Furthermore, T-SOD activity in serum of the pregnant rats increased and the levels of MDA and NO decreased in the combined supplementation group. Our study indicates the neuroprotection of FA and SIF combined administration is superior to solo treatment. Decrease of DNA damage and neuron apoptosis involved in the mechanisms. Furthermore, the up-regulation of Bcl-2 and the down-regulation of Bax and P53 proteins also participate in the effect.

Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression.

We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.

Inhibition of cyclophoshamide-induced mutagenicity by microsized powder of selenium-enriched green tea in mice.

Previously, the antioxidant activity of Se-enriched green tea extracts has been studied in vitro. In the present study, an in vivo micronuclei test was employed to assess the antimutagenic effect of microsized Se-enriched green tea powder (MSTP) in mice bone marrow. Pretreatments of MSTP, micrometer-sized regular tea powder (MRTP), selenite, and MRTP + selenite were given by gavage for 29 consecutive days prior to cyclophoshamide (CP) treatment. Certain key antioxidant enzymes were also investigated to elucidate the mechanism of antimutagenic effect. Results indicated that MSTP and MRTP or selenite alone did not significantly induce micronuclei at either concentration, confirming its nonmutagenicity. In the CP-treated groups, significant suppressions in the micronuclei were recorded following pretreatment with MSTP, MRTP, and selenite administration. The antimutagenic effect of MSTP was evidently observed by significant reduction in the frequencies of micronuclei in bone marrow cells when compared to a positive control group. The administration of MSTP, selenite, and MRTP + selenite also increased the levels of selenium concentration, glutathione peroxidase (GPx), and superoxide dismutase (SOD) enzymes in both blood and liver. However, no pronounced differences in activities of GPx and SOD were found among MSTP, selenite, and MRTP + selenite. The present findings demonstrate that the antimutagenic potential of MSTP could not be solely related to the enhancment of antioxidant enzymes of GPx and SOD.

Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells.

BACKGROUND: Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent for the cancer patients to reduce the side effects in the clinic application. Because CP is a pro-oxidant agent and induces oxidative stress by the generation of free radicals to decrease the activities of anti-oxidant enzymes, the protective effects of the total saponins from stem and leaf of P. ginseng C.A. Meyer (TSPG) act as an anti-oxidant agent against the decreased anti-oxidant enzymes, the genotoxicity and apoptosis induced by CP was carried out. METHODS: The alkaline single cell gel electrophoresis was employed to detect DNA damage; flow cytometry assay and AO/EB staining assay were employed to measure cell apoptosis; the enzymatic anti-oxidants (T-SOD, CAT and GPx) and non-enzymatic anti-oxidant (GSH) were measured by the various colorimetric methods. RESULTS: CP induced the significant DNA damage in mouse peripheral lymphocytes in time- and dose-dependent manners, inhibited the activities of T-SOD, GPx and CAT, and decreased the contents of GSH in mouse blood, triggered bone marrow cell apoptosis at 6 and 12h. TSPG significantly reduced CP-induced DNA damages in bone marrow cells and peripheral lymphocyte cells, antagonized CP-induced reduction of T-SOD, GPx, CAT activities and the GSH contents, decreased the bone marrow cell apoptosis induced by CP. CONCLUSIONS: TSPG, significantly reduced the genotoxicity of CP in bone marrow cells and peripheral lymphocyte cells, and decreased the apoptotic cell number induced by CP in bone marrow cells. The effects of TSPG on T-SOD, GPx, CAT activities and GSH contents might partially contribute to its protective effects on CP-induced cell toxicities.

Evaluation of the chemoprotective effect of Biophytum sensitivum (L.) DC extract against cyclophosphamide induced toxicity in Swiss albino mice.

An alcoholic extract of Biophytum sensitivum was studied against cyclophosphamide (CTX) induced toxicity in mice. Intraperitoneal administration of the extract with CTX significantly increased the total WBC count (3,356 +/- 236 cells/cm2), bone marrow cellularity (15.6 +/- 0.42 cells/femur) and alpha-esterase positive cells (846 +/- 30 cells) when compared to control mice treated with CTX alone. The relative organ weight of the spleen and thymus was also found to be increased after B. sensitivum administration when compared to the control mice. Reduction of GSH in liver (4.9 +/- 0.22 nmol/mg protein) and in intestinal mucosa (10.6 +/- 1.02 nmol/mg protein) of CTX treated controls was significantly reversed by B. sensitivum administration (liver: 6.5 +/- 0.18 nmol/mg protein; intestinal mucosa: 16.5 +/- 0.88 nmol/mg protein), with amelioration of changes in serum and liver ALP, GPT and lipid peroxidation. Histopathological analysis of the small intestine also suggests that B. sensitivum could reduce CTX induced intestinal damage. The level of the pro-inflammatory cytokine, TNF-alpha, which was elevated during CTX administration, was significantly reduced by the administration of B. sensitivum extract. The lowered levels of cytokines IFN-gamma, IL-2 and GM-CSF after CTX treatment were also found to be increased by B. sensitivum extract administration.