Effect of Terminalia arjuna extract on adriamycin-induced DNA damage.

The effect of a bark extract of Terminalia arjuna (TAE) was studied on the alteration of adriamycin (ADR)-induced micronuclei formation in cultured human peripheral blood lymphocytes. Exposure of lymphocytes to ADR resulted in a dose-dependent increase in the micronuclei formation indicating DNA damage. Pretreatment of lymphocytes with TAE before ADR treatment resulted in a significant decline in micronuclei formation. Increasing doses of ADR caused a dose-dependent increase in the frequency of lymphocytes bearing one, two and multiple micronuclei. Prior exposure of lymphocytes to 15 microg/mL of TAE significantly reduced the frequency of lymphocytes bearing one, two and multiple micronuclei when compared with ADR-treated control. TAE-inhibited the induction of (*)OH (hydroxyl), O2(*-) (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS(*+) (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. These results demonstrate that TAE protects DNA against ADR-induced damage.

Antarth, a polyherbal preparation protects against the doxorubicin-induced toxicity without compromising its Antineoplastic activity.

Doxorubicin (DOX), an anthracycline drug widely used for the treatment of various cancers, causes a cumulative dose-dependent cardiotoxicity that is characterized by an irreversible dilated cardiomyopathy and congestive heart failure. Antarth (ANT) a polyherbal preparation was evaluated for its cardioprotective properties against doxorubicin-induced cardiotoxicity in mice. Mice were treated with 25 mg/kg ANT orally once daily for 5 consecutive days before a single intraperitoneal injection of 15 mg/kg doxorubicin. The animals were killed 30 h after DOX treatment. DOX induced a significant elevation in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase (CK-MB) and lactate dehydrogenase (LDH), indicating its acute cardiotoxicity. The treatment of mice with ANT before DOX administration significantly reduced the serum levels of GPT, GOT, CK-MB and LDH indicating that ANT protected against the DOX-induced cardiotoxicity. Pretreatment of mice with 25 mg/kg ANT inhibited the DOX-induced decline in the antioxidant status. Intraperitoneal injection of 1.25 mg/kg DOX once daily for 9 consecutive days significantly improved the survival of mice bearing Ehrlich ascites carcinoma (EAC). Treatment of EAC with 25 mg/kg ANT alone did not affect the anticancer activity of DOX since ANT did not alter the tumor cell growth, the median survival time and average survival time of tumor bearing mice. The present study demonstrates that ANT protects mice against DOX-induced cardiotoxicity, without compromising the antineoplastic activity of DOX.

Antarth, a polyherbal preparation protects against the doxorubicin-induced toxicity without compromising its antineoplastic activity

Doxorubicin (DOX), an anthracycline drug widely used for the treatment of various cancers, causes a cumulative dose-dependent cardiotoxicity that is characterized by an irreversible dilated cardiomyopathy and congestive heart failure. Antarth (ANT) a polyherbal preparation was evaluated for its cardioprotective properties against doxorubicin-induced cardiotoxicity in mice. Mice were treated with 25 mg/kg ANT orally once daily for 5 consecutive days before a single intraperitoneal injection of 15 mg/kg doxorubicin. The animals were killed 30 h after DOX treatment. DOX induced a significant elevation in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase (CK-MB) and lactate dehydrogenase (LDH), indicating its acute cardiotoxicity. The treatment of mice with ANT before DOX administration significantly reduced the serum levels of GPT, GOT, CK-MB and LDH indicating that ANT protected against the DOX-induced cardiotoxicity. Pretreatment of mice with 25 mg/kg ANT inhibited the DOX-induced decline in the antioxidant status. Intraperitoneal injection of 1.25 mg/kg DOX once daily for 9 consecutive days significantly improved the survival of mice bearing Ehrlich ascites carcinoma (EAC). Treatment of EAC with 25 mg/kg ANT alone did not affect the anticancer activity of DOX since ANT did not alter the tumor cell growth, the median survival time and average survival time of tumor bearing mice. The present study demonstrates that ANT protects mice against DOX-induced cardiotoxicity, without compromising the antineoplastic activity of DOX.

Modulation of radiation-induced alteration in the antioxidant status of mice by naringin.

The alteration in the antioxidant status and lipid peroxidation was investigated in Swiss albino mice treated with 2 mg/kg b.wt. naringin, a citrus flavoglycoside, before exposure to 0.5, 1, 2, 3, and 4 Gy gamma radiation. Lipid peroxidation, glutathione, glutathione peroxidase, catalase and superoxide dismutase were determined in the liver and small intestine of mice treated or not with naringin at 0.5, 1, 2, 4 and 8 h post-irradiation. Whole-body irradiation of mice caused a dose-dependent elevation in the lipid peroxidation while a dose-dependent depletion was observed for glutathione, glutathione peroxidase, superoxide dismutase and catalase in both liver as well as small intestine. Treatment of mice with 2 mg/kg b. wt. naringin inhibited the radiation-induced elevation in the lipid peroxidation as well as depletion of glutathione, glutathione peroxidase, superoxide dismutase and catalase in liver and small intestine. Radiation-induced lipid peroxidation increased with time, which was greatest at 2 h post-irradiation and declined thereafter in the liver and small intestine. Similarly, a maximum decline in the glutathione glutathione peroxidase, and superoxide dismutase was observed at 1 h, while catalase showed a maximum decline at 2 h post-irradiation. Our study demonstrates that naringin protects mouse liver and intestine against the radiation-induced damage by elevating the antioxidant status and reducing the lipid peroxidation.

Influence of naringin on ferric iron induced oxidative damage in vitro.

BACKGROUND: Iron is essential for oxygen transport and a variety of cellular processes like respiration and DNA synthesis. It may become toxic when not handled carefully by cellular proteins and shielded from surrounding media. Naringin treatment may help to overcome the iron-induced toxic effects in vitro. METHODS: HepG2 cells were treated with 0.5, 1, 2.5, and 5 mmol/l naringin 1 h before exposure to 0.1, 0.25, 0.5, and 1 mmol/l ferric iron. The effect of iron or naringin or their combination treatment was studied on cell survival, DNA double-strand break induction, DNA oxidation, lipid peroxidation, and various antioxidants. RESULTS: The exposure of cells to iron caused a dose-dependent decline in their clonogenic potential, while naringin pretreatment resulted in a significant elevation in the cell survival. Exposure of cells to iron resulted in a time-dependent elevation in DNA strand breaks and a peak level of DNA strand breaks was observed at 24 h, while naringin pretreatment inhibited the DNA double-strand breaks accompanied by an early repair. Similarly, treatment of HepG2 cells with iron caused increased DNA oxidation that showed reduction when cells were pretreated with naringin. The iron overload caused a significant elevation in the lipid peroxidation accompanied by depletion in glutathione (GSH) concentration, while naringin inhibited lipid peroxidation and arrested the iron-induced depletion in the GSH concentration. Iron treatment also reduced various antioxidant enzymes like glutathione peroxidase (GSHPx), catalase, and superoxide dismutase (SOD). Pretreatment of HepG2 cells with naringin resulted in an elevation in all the antioxidant enzymes. CONCLUSIONS: Enhanced antioxidant status by naringin could compensate the oxidative stress and may facilitate an early recovery from iron-induced genomic insult in vitro.

The evaluation of the acute toxicity and long term safety of hydroalcoholic extract of Sapthaparna (Alstonia scholaris) in mice and rats.

The acute and sub-acute toxic effects of various doses of hydroalcoholic extract of Alstonia scholaris (ASE) was studied in mice and rats. The acute toxicity in mice depended on the season of collection of plant. The highest acute toxicity was observed in the ASE prepared from the summer collection followed by winter. The least toxicity was observed in the extract prepared from the bark of A. scholaris collected in the monsoon season. The administration of different doses of ASE showed a dose dependent increase in the toxicity in all species of mice. The Swiss albino mice were found to be the most sensitive followed by the DBA and C(57)BL. The crossbred mice were resistant when compared to the pure inbred strains. The oral administration of ASE was non-toxic up to a dose of 2000 mg/kg b. wt., while maximum number of animals succumbed to death after administration of 1100 mg/kg ASE by intraperitoneal route. The rats were more sensitive than the mice as the LD(50) dose of ASE was lesser for the former than the latter. The sub-acute toxicity in the rats was carried out with 120 and 240 mg/kg b. wt. ASE (1/10th and 1/5th of the LD(50) dose of ASE). The 240 mg was observed to be more toxic than 120 mg/kg ASE since it caused mortality and deformity in various organs of the recipient animals. The various biochemical parameters like AST, ALT, ACP, ALP, CK, LDH, creatinine, urea, ammonia, glucose and LPx were higher at 240 mg/kg ASE when compared with the 120 mg and the non-drug treated animals. In contrast, the total protein, albumin, DNA, RNA, cholesterol, glucose, glutathione, total thiols declined in the 240 mg/kg ASE treated animals when compared with non-drug treated controls. The hematological analysis showed a dose dependent decrease in the RBC, WBC, hemoglobin, neutrophils and monocytes, while a significant increase in the lymphocytes, eosinophils and basophils was observed. The observed toxic effect of ASE may be due to the presence of echitamine. Our studies shows that at high doses, A. scholaris exhibited marked damage to all the major organs of the body.

Naringin, a citrus flavonone, protects against radiation-induced chromosome damage in mouse bone marrow.

Free radicals are responsible for the induction of damage to the cellular DNA that leads to the formation of chromosome aberrations. Antioxidants are known to scavenge free radicals, thereby decreasing the degree of such effects. Radiation is a well-known inducer of free radicals and compounds that can scavenge free radicals may reduce radiation-induced DNA damage. Naringin, a bioflavonoid predominant in grapefruit and other citrus fruits, has been found to scavenge free radicals, therefore it may also reduce radiation-induced damage. The aim of the present study was to evaluate the radioprotective action of 2 mg/kg naringin in the bone marrow of mice exposed to different doses of (60)Co gamma-radiation by scoring the frequency of asymmetrical chromosomal aberrations. The irradiation of mice resulted in a dose-dependent elevation in the frequency of aberrant cells, acentric fragments, chromatid and chromosome breaks, dicentrics and exchanges. All these aberrations were elevated with scoring time up to 24 h post-irradiation and declined thereafter, except chromatid breaks, which were maximum at 12 h post-irradiation. Treatment of mice with 2 mg/kg body wt naringin before exposure to various doses of gamma-radiation resulted in a significant reduction in the frequencies of aberrant cells and chromosomal aberrations like acentric fragments, chromatid and chromosome breaks, centric rings, dicentrics and exchanges. The evaluation of free radical scavenging activity of naringin revealed a dose-dependent scavenging of hydroxyl, superoxide and 2,2 equal to or precedes -diphenyl-1-picryl hydrazyl radical. Naringin at 5 microM scavenged the 2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid cation radical very efficiently, where a 90% scavenging was observed. Our study demonstrates that naringin can protect mouse bone marrow cells against radiation-induced chromosomal damage.

The grapefruit flavanone naringin protects against the radiation-induced genomic instability in the mice bone marrow: a micronucleus study.

The effect of various doses, viz. 0, 0.5, 1, 2, 4, 6 and 8 mg/kg body weight of naringin (NIN) (a citrus flavanone) was studied on the alteration in the radiation-induced micronucleated polychromatic (MPCE) and normochromatic (MNCE) erythrocytes in mouse bone marrow exposed to 2 Gy of 60Co gamma-radiation. The treatment of mice with various doses of NIN before exposure to 2 Gy resulted in a significant decline in the frequency of MPCE when compared to the non-drug-treated irradiated control. However, the greatest reduction in MPCE was observed for 2mg/kg body weight NIN, accompanied by a highest PCE/NCE ratio when compared with the non-drug-treated irradiated control. Therefore, further studies were carried out using this dose of NIN, where the animals were administered with 2mg/kg body weight of NIN before exposure to 0, 0.5, 1, 2, 3 and 4 Gy of gamma-radiation. The frequency of MPCE and MNCE increased in a dose-dependent manner in both the non-drug-treated irradiated control and NIN-pretreated irradiated groups up to a dose of 2 Gy, while a further increase in the irradiation dose resulted in a significant decline in MPCE and MNCE frequencies in both groups. Pretreatment of mice with 2mg/kg body weight of NIN resulted in a significant decline in the frequencies of MPCE and MNCE. NIN treatment not only reduced the frequency of MPCE with one micronucleus, but also of MPCE with multiple micronuclei (MN), indicating its ability to reduce complex chromosome aberrations. Conversely, the PCE/NCE ratio declined in a dose-dependent manner in both groups. The treatment of mice with NIN before exposure to different doses of gamma-radiation resulted in the inhibition in this decline in the PCE/NCE ratio. Our study demonstrates that NIN is able to protect mouse bone marrow cells against the radiation-induced DNA damage and decline in the cell proliferation as observed by a reduction in the micronucleus frequency and an increase in PCE/NCE ratio, respectively, in the NIN-pretreated irradiated group.