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The use of wireless communication technology in mobile phones has revolutionized modern telecommunication and mobile phones have become so popular that their number exceeds the global population. Electromagnetic field radiations (EMR) are an integral part of wireless technology, which are emitted by mobile phones, mobile tower antennas, electric power stations, transmission lines, radars, microwave ovens, television sets, refrigerators, diagnostic, therapeutic, and other electronic devices. Manmade EMR sources have added to the existing burden of natural EMR human exposure arising from the Sun, cosmos, atmospheric discharges, and thunder storms. EMR including radiofrequency waves (RF) and extremely low-frequency radiation (ELF) has generated great interest as their short-term exposure causes headache, fatigue, tinnitus, concentration problems, depression, memory loss, skin irritation, sleep disorders, nausea, cardiovascular effects, chest pain, immunity, and hormonal disorders in humans, whereas long-term exposure to EMR leads to the development of cancer. The review has been written by collecting the information using various search engines including google scholar, PubMed, SciFinder, Science direct, EMF-portal, saferemr, and other websites from the internet. The main focus of this review is to delineate the mutagenic and genotoxic effects of EMR in humans and mammals. Numerous investigations revealed that exposure in the range of 0-300 GHz EMR is harmless as it did not increase micronuclei and chromosome aberrations. On the contrary, several other studies have demonstrated that exposure to EMR is genotoxic and mutagenic as it increases the frequency of micronuclei, chromosome aberrations, DNA adducts, DNA single and double strand breaks at the molecular level in vitro and in vivo. The EMR exposure induces reactive oxygen species and changes the fidelity of genes involved in signal transduction, cytoskeleton formation, and cellular metabolism., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Wound injury is common and causes serious complications if not treated properly. The moist dressing heals wounds faster than other dressings. Therefore, we sought to study the effect of hesperidin/naringin hydrogel wound dressing or their combinations on the deep dermal wounds in mice., Methods: A rectangular full thickness skin flap of 2.5 × 1.5 cm was excised from depilated mice dorsum and the wound was fully covered with 5% hesperidin/5% naringin hydrogel or both in the ratio of 1:1, 2:1, or 1:2, respectively once daily until complete healing of the wound. Data were collected on wound contraction, mean wound healing time, collagen, DNA, and nitric oxide syntheses, glutathione concentration, superoxide dismutase activity, and lipid peroxidation throughout healing. Expression of NF-κB and COX-2 were also estimated in the regenerating granulation tissue using Western blot., Findings: Dressing of wounds with 5% hesperidin hydrogel led to a higher and early wound contraction and significantly reduced mean wound healing time by 5.7 days than 5% naringin or combination of hesperidin and naringin hydrogels in the ratio of 1:1, 2:1, or 1:2. Hesperidin hydrogel wound dressing caused higher collagen and DNA syntheses than other groups at all times after injury. Glutathione concentration and superoxide dismutase activity increased followed by a decline in lipid peroxidation in regenerating wounds after hesperidin/naringin hydrogel application and a maximum effect was observed for hesperidin alone. The hesperidin/naringin hydrogel suppressed NF-κB and COX-2 expression on days 6 and 12., Conclusions: Application of 5% hesperidin hydrogel was more effective than 5% naringin or combination of hesperidin and naringin gels (1:1, 2:1 or 1:2) indicated by a greater wound contraction, reduced mean wound healing time, elevated collagen and DNA syntheses, rise in glutathione concentration, and superoxide dismutase activity followed by reduced lipid peroxidation, and NF-κB, and COX-2 expression., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Oroxylum indicum (Sonapatha) is traditionally used to cure several human ailments. Therefore, the cell killing effect of chloroform, ethanol, and water extracts of Sonapatha was studied in cultured HeLa cells treated with 0-100 µg/mL of these extracts/doxorubicin by MTT assay. Since ethanol extract was most cytotoxic its effect was further investigated by clonogenic, apoptosis, necrosis, and lactate dehydrogenase assays. The mechanism of cytotoxicity of Sonapatha was determined at the molecular level by estimation of caspase 8 and 3 activities and Western blot analysis of NF-κB, COX-2, Nrf2, and RASSF7 which are overexpressed in neoplastic cells. HeLa cells treated with Sonapatha extract exhibited a concentration and time-dependent rise in the cytotoxicity as indicated by the MTT assay. Ethanol extract of Sonapatha (0, 20, 40, and 80 μg/mL) reduced clonogenicity, increased DNA fragmentation, apoptotic and necrotic indices, lactate dehydrogenase release, caspase 8 and 3 activities and inhibited the overexpression of NF-κB, COX-2, Nrf2, and RASSF7 in HeLa cells concentration-dependently., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Ionizing radiations trigger the formation of free radicals that damage DNA and cause cell death. DNA damage may be simply evaluated by micronucleus assay and the pharmacophores that impede free radicals could effectively reduce the DNA damage initiated by irradiation. Therefore, it was desired to determine the capacity of curcumin to alleviate micronuclei formation in human peripheral blood lymphocytes (HPBLs) exposed to 0-4 Gy of γ-radiation., Materials and Methods: HPBLs were exposed to 3 Gy after 30 minutes of 0.125, 0.25, 0.5, 1, 2, 5, 10, 20 or 50 µg/mL curcumin treatment or with 0.5 μg/mL curcumin 30 minutes early to 0, 0.5, 1, 2, 3 or 4 Gy 60 Co γ-irradiation. Cytokinesis of HPBLs was blocked by cytochalasin B and micronuclei scored. The ability of curcumin to suppress free radical induction in vitro was determined by standard methods., Results: HPBLs treated with different concentrations of curcumin before 3 Gy irradiation alleviated the micronuclei formation depending on curcumin concentration and the lowest micronuclei were detected at 0.5 µg/mL curcumin when compared to 3 Gy irradiation alone. Increasing curcumin concentration caused a gradual rise in micronuclei, and the significant increases were detected at 10-50 µg/mL curcumin than 3 Gy irradiation alone. Irradiation of HPBLs to different doses of γ-rays caused a significant rise in micronuclei depending on radiation dose, whereas HPBLs treated with 0.5 µg/mL curcumin 30 minutes before irradiation to different doses of γ-rays significantly reduced frequencies of HPBLs with one, two, or more micronuclei. Curcumin treatment inhibited the formation of hydroxyl (OH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and (nitric oxide) NO free radicals in a concentration-related way., Conclusions: Curcumin when treated at a dose of 0.5 μg/mL attenuated micronuclei formation after γ-irradiation by inhibiting the formation of radiation-induced free radicals.

We examined the effects of administration of (E) 4-[4-N,N-dimethylaminophenyl]but-3-en-2-one (DMAP) on radiation-induced chromosome damage in mice. Mice were whole-body exposed to γ-rays, 0-4 Gy, and then immediately administered DMAP, 20 mg/kg. After 24 h, mice were sacrificed, femora were removed, marrow was extracted, and chromosome aberrations were scored in the bone marrow cells. With vehicle-only (saline or oil) treatment, radiation dose-dependent damage was seen in aberrant cells, chromosome breaks, chromatid breaks, centric rings, di-, tri-, and tetracentrics, acentric fragments, total aberrations, polyploidy, and pulverization. Post-administration of DMAP was protective as it reduced chromosome damage. DMAP treatment may be a useful protective agent following radiation accidents or radiotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The cancer-protective ability of hesperidin was investigated on 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin carcinogenesis in Swiss albino mice. Topical application of DMBA+TPA on mice skin led to 100% tumour incidence and rise in average number of tumours. Administration of different doses of hesperidin (HPD) before (pre) or after (post) and continuous (pre and post) DMBA application significantly reduced tumour incidence and average number of tumours in comparison to DMBA+TPA treatment alone. Topical application of DMBA+TPA increased oxidative stress as shown by significantly increased TBARS values and reduced glutathione contents, and glutathione-S-transferase, superoxide dismutase and catalase activities. Hesperidin treatment significantly reduced TBARS values and elevated glutathione concentration and glutathione-S-transferase, superoxide dismutase and catalase activities in the skin/tumors of mice treated with HPD+DMBA+TPA, HPD+DMBA+TPA+HPD or DMBA+TPA+HPD when compared to DMBA+TPA application alone. The study of molecular mechanisms showed that hesperidin suppressed expression of Rassf7, Nrf2, PARP and NF-κB in a dose dependent manner with a maximum inhibition at the level of 300 mg/kg body weight hesperidin. In conclusion, oral administration of hesperidin protected mice against chemical carcinogenesis by increasing antioxidant status, reducing DMBA+TPA induced lipid peroxidation and inflammatory response, and repressing of Rassf7, Nrf2, PARP and NF-κB levels., (© 2019 Published by Elsevier Ltd.)

Purpose: The regular low dose occupational exposure to ionizing radiation may induce deleterious health effects, which may be of particular interest to medical radiation workers who daily handle X-ray machines. Human peripheral blood lymphocytes are able to retain the signature of radiation-induced DNA damage, therefore, the present study was undertaken to investigate the DNA damage and antioxidants status in hospital workers occupationally exposed to low doses of X-rays. Materials and methods: The peripheral blood lymphocytes of the occupationally exposed and control groups matched for age, gender, tobacco usage, and alcohol consumption were cultured and micronuclei frequency was determined. Activities of antioxidant enzymes and lipid peroxidation were also estimated in their plasma. Results: The micronuclei frequency in the occupationally exposed group ( n  = 33), increased significantly ( p  < .0001) followed by reduced glutathione-s-transferase ( p  < .01) and catalase ( p  < .001) activities, and increased lipid peroxidation ( p  < .05) when compared to the control group ( n  = 33). Occupational exposure resulted in an effective dose ranging between 3.14 to 144.5 mSv (40.88 ± 39.86mSv) depending on the employment duration of 3-29 years (10.33 ± 7.05 years). A correlation between the micronuclei frequency ( p  < .05) and catalase activity ( p  < .05) existed in the occupationally exposed individuals depending on the smoking habit, age, duration of employment, cumulative exposure dose and number of patients handled per day. Conclusions: We have observed that protracted low dose exposure to ionizing radiation is an inevitable occupational hazard leading to persistence of oxidative stress and increased genomic instability in the radiological technicians depending on the time spent with X-rays, cumulative dose received and the number of patients handled daily raising the risk of cancer development.

Ethnopharmacological Relevance: The Oroxylum indicum is used traditionally to treat fever, colic, stomach ulcers, constipation, indigestion, intestinal worms, strangury, asthma, cough, hiccough, diarrhea, dysentery and wounds by the herbal healers of Mizoram and it is also part of Ayurvedic formulations., Aims of the Study: The wound healing activity of Oroxylum indicum has not been investigated. Therefore, the present study was undertaken to evaluate the ability of different concentrations of ethanol extract of stem bark of Oroxylum indicum in the deep dermal excision wounds of mice., Materials and Methods: The deep dermal excision wound was created on the shaved dorsum of Swiss albino mice. Each excision wound was topically applied with 5%, 10%, 20% or 30% gel of stem bark ethanol extract of Oroxylum indicum (OIE) and wound contraction, mean wound healing time (MHT), collagen and DNA syntheses were studied. The expression of NF-κB and COX-II were evaluated in the regenerating wound granulation tissues of mice., Results: Topical application of different concentrations of OIE resulted in a concentration dependent rise in wound contraction and MHT and the highest wound contraction was recorded for 10% OIE. Similarly, topical application of different concentrations of OIE increased the DNA and neocollagen syntheses in a dose dependent manner at all post wounding days and the greatest acceleration in DNA and neocollagen formation was observed for 10% OIE. The evaluation of lipid peroxidation (LOO) showed a dose dependent decline in LOO, which was lowest for 10% OIE. The study of molecular mechanisms revealed the suppression of NF-κB and COX-II in a dose dependent manner in the regenerating wound of mice with a maximum inhibition at 10% OIE., Conclusions: The present study demonstrates that OIE accelerated the wound contraction and reduced mean wound healing time in mice, which may be due to increased collagen and DNA syntheses, reduced lipid peroxidation coupled by NF-κB and COX-II suppression by OIE in the regenerating wounds of mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Free radicals are an outcome of various metabolic activities and their excess production leads to many diseases. Therefore, it is necessary to neutralize excess free radicals., Materials & Methods: Free-radical scavenging activity of various extracts of Schima wallichii was evaluated using standard protocols., Results: Chloroform, ethanol and aqueous extracts of S. wallichii scavenged DPPH, hydroxyl, superoxide, nitric oxide and ABTS free radicals and increased ferric-reducing antioxidant potential in a concentration-dependent manner. A total of 1000 μg/ml of all the extracts and ethanol extract showed highest total flavonoids and phenol contents, respectively., Conclusion: The different extracts of S. wallichii scavenged different free radicals efficiently due to the presence of flavonoids and polyphenols and may be helpful in free radical-induced diseases., Competing Interests: Financial & competing interests disclosure The authors are thankful to the University Grants Commission and Department of Biotechnology, Government of India, New Delhi for providing financial assistance to carry out this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Radiofrequency radiations (RFRs) emitted by mobile phone base stations have raised concerns on its adverse impact on humans residing in the vicinity of mobile phone base stations. Therefore, the present study was envisaged to evaluate the effect of RFR on the DNA damage and antioxidant status in cultured human peripheral blood lymphocytes (HPBLs) of individuals residing in the vicinity of mobile phone base stations and comparing it with healthy controls. The study groups matched for various demographic data including age, gender, dietary pattern, smoking habit, alcohol consumption, duration of mobile phone use and average daily mobile phone use. The RF power density of the exposed individuals was significantly higher (p < 0.0001) when compared to the control group. The HPBLs were cultured and the DNA damage was assessed by cytokinesis blocked micronucleus (MN) assay in the binucleate lymphocytes. The analyses of data from the exposed group (n = 40), residing within a perimeter of 80 m of mobile base stations, showed significantly (p < 0.0001) higher frequency of micronuclei when compared to the control group, residing 300 m away from the mobile base station/s. The analysis of various antioxidants in the plasma of exposed individuals revealed a significant attrition in glutathione (GSH) concentration (p < 0.01), activities of catalase (CAT) (p < 0.001) and superoxide dismutase (SOD) (p < 0.001) and rise in lipid peroxidation (LOO) when compared to controls. Multiple linear regression analyses revealed a significant association among reduced GSH concentration (p < 0.05), CAT (p < 0.001) and SOD (p < 0.001) activities and elevated MN frequency (p < 0.001) and LOO (p < 0.001) with increasing RF power density.

Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha. The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders.

Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain better therapeutic gains. Curcumin is an antioxidant and a free radical scavenging dietary supplement, commonly used as a flavoring agent in curries. Therefore, the effect of 100 mg/kg body weight curcumin was studied on the antioxidant status of mice skin exposed to a total dose of 10, 20 and 40 Gy γ-radiation below the rib cage delivered as a single fraction of 2 Gy per day for 5, 10 or 20 days. Skin biopsies from both the curcumin treated or untreated irradiated groups were collected for the biochemical estimations at various post-irradiation times. The irradiation of animals caused a dose dependent decline in the glutathione concentration, glutathione peroxidase, and superoxide dismutase activities and increased the lipid peroxidation in the irradiated skin. Curcumin treatment before irradiation resulted in a significant rise in the glutathione concentration and activities of both the glutathione peroxidase and superoxide dismutase enzymes in mouse skin, whereas lipid peroxidation declined significantly. The present study indicates that curcumin treatment increased the antioxidant status of mouse exposed to different doses of fractionated γ-radiation.

The radioprotective property of 50 mg/kg body weight jamun (Syzygium cumini) extract was studied in the cultured splenocytes of mice exposed to 0, 0.5, 1, 2, 3, or 4 Gy of γ-radiation. The spleens of irradiated mice were removed aseptically and the splenocytes were extracted from the individual spleens and cultured. The micronuclei were prepared 72 hours after irradiation in binucleate splenocytes by blocking cytokinesis with cytochalasin-B. Irradiation of mice resulted in a dose-dependent elevation in the micronucleated splenocytes. The exposure of mice not only elevated splenocytes bearing one micronucleus but also cells bearing 2 and multiple (>2) micronuclei indicating induction of complex DNA damage after irradiation. Oral treatment of mice with 50 mg/kg body weight of jamun leaf extract protected against the radiation-induced micronuclei formation. Jamun extract also protected against the formation of 2 and multiple micronuclei indicating repair or inhibition of complex DNA damage. The assessment of lipid peroxidation in mice brain homogenate has indicated a concentration dependent inhibition of lipid peroxidation by jamun extract. Studies in a cell free system revealed that jamun extract inhibited the formation of OH, O(2)-, DPPH, and ABTS(+) free radicals in a concentration dependent manner. Our study demonstrates that jamun extract protected mice against the radiation-induced DNA damage and inhibition of radiation-induced free radical formation may be one of the mechanisms of radioprotection.

Fractionated irradiation (IR) before or after surgery of malignant tumours causes a high frequency of wound healing complications. Our aim was to investigate the effect of curcumin (CUM) on the healing of deep excision wound of mice exposed to fractionated IR by mimicking clinical conditions. A full-thickness dermal excision wound was created on the shaved dorsum of mice that were orally administered or not with 100 mg of CUM per kilogram body weight before partial body exposure to 10, 20 or 40 Gy given as 2 Gy/day for 5, 10 or 20 days. The wound contraction was determined periodically by capturing video images of the wound from day 1 until complete healing of wounds. Fractionated IR caused a dose-dependent delay in the wound contraction and prolonged wound healing time, whereas CUM administration before fractionated IR caused a significant elevation in the wound contraction and reduced mean wound healing time. Fractionated IR reduced the synthesis of collagen, deoxyribonucleic acid (DNA) and nitric oxide (NO) at different post-IR times and treatment of mice with CUM before IR elevated the synthesis of collagen, DNA and NO significantly. Histological examination showed a reduction in the collagen deposition, fibroblast and vascular densities after fractionated IR, whereas CUM pre-treatment inhibited this decline significantly. Our study shows that CUM pre-treatment accelerated healing of irradiated wound and could be a substantial therapeutic strategy in the management of irradiated wounds., (© 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. The protective effect of naringin, a grape fruit flavanone, was studied in iron overloaded isolated mouse liver mitochondria, where the isolated mitochondrial fraction was incubated with various concentrations of naringin before ferric ion loading. Iron overloading of mitochondrial fraction resulted in an increase in lipid peroxidation, protein oxidation, and DNA damage, whereas iron overload reduced the glutathione (GSH) concentration, glutathione-S-transferase (GST), glutathione peroxidase (GSHPx), catalase and superoxide dismutase (SOD) activities. Pretreatment of mitochondrial fraction with naringin inhibited iron-induced lipid peroxidation, protein oxidation, and DNA damage. Conversely, naringin supplementation arrested iron-induced depletion in the GSH contents, GSHPx, GST, SOD and catalase activities significantly. Ferric iron reduction assay revealed that naringin could not reduce ferric iron into ferrous iron indicating that it did not exhibit prooxidant activity. Iron free coordination site assay indicated that naringin was unable to occupy all the active sites of iron indicating that naringin did not completely chelate iron. Our study demonstrates that naringin was able to share the burden of endogenous oxidants by inhibiting the iron-induced depletion of all important antioxidant enzymes as well as GSH and may act as a good antioxidant., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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.

Because of the practical importance of acute radiation exposure associated with combined injuries, it is imperative to investigate the efficacy of cost-effective nutritional factors in the reconstruction of irradiated wounds. Therefore, effect of pretreatment of ascorbic acid was studied on the healing of excised wounds in mice exposed to 2, 4, 6 and 8 Gy whole body gamma-radiation. A full-thickness wound was created on the dorsum of the irradiated mice and the progression of wound contraction was monitored by capturing video images of the wound at various varying days after irradiation. Irradiation caused a dose dependent delay in wound contraction and wound healing time, while ascorbic acid pretreatment resulted in a significant acceleration in the rate of wound contraction and a decrease in the mean wound healing time. To understand the mechanism of healing, collagen, hexosamine, DNA, nitrite and nitrate contents were measured in the granulation tissue of wounded mice treated with ascorbic acid before exposure to 6 Gy gamma-radiation. Ascorbic acid treatment prior to irradiation enhanced the synthesis of collagen, hexosamine, DNA, nitrite and nitrate contents. The histological assessment of wound biopsy revealed an improved collagen deposition, and increase in fibroblast and vascular densities. The present study demonstrates that ascorbic acid pretreatment has a beneficial effect on the irradiated wound and could be a substantial therapeutic strategy to accelerate wound repair in irradiated wounds and in the cases of combined injury situations.

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.

The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced genomic damage and alteration in the survival of cultured V79 cells. Exposure of V79 cells to bleomycin induced a concentration dependent elevation in the frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of MNBNCs were observed in the cells treated with 50 microg ml(-1) bleomycin, the highest concentration evaluated. This genotoxic effect of bleomycin was reflected in the cell survival, where a concentration dependent decline was observed in the cells treated with different concentrations of bleomycin. Treatment of cells with 1 mm naringin before exposure to different concentrations of bleomycin arrested the bleomycin-induced decline in the cell survival accompanied by a significant reduction in the frequency of micronuclei when compared with bleomycin treatment alone. The cell survival and micronuclei induction were found to be inversely correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated by exposing the cells to 10 microg ml(-1) bleomycin using single cell gel electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration of more DNA into the tails (% tail DNA) of the comets and a subsequent increase in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1 mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as indicated by a reduction in % tail DNA and OTM with increasing assessment time. A maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment, where it was 5 times lower than bleomycin alone. Our study, which was conducted on the basis of antioxidant, free radical scavenging and metal chelating properties of naringin demonstrates that naringin reduced the genotoxic effects of bleomycin and consequently increased the cell survival and therefore may act as a chemoprotective agent in clinical situations.

The frequency of micronucleated polychromatic (MPCE), normochromatic erythrocytes (MNCE), and polychromatic/normochromatic erythrocyte ratio (PCE/NCE), was studied in the bone marrow of mice orally administered with 0, 200, 225, 250, 275 and 300 mg/kg body weight of hydroalcoholic leaf extract of Aegle marmelos (AME). Treatment of mice with AME, once daily for 5 consecutive days, before exposure to 2 Gy resulted in a significant decline in the frequency of MPCE when compared to the non-drug-treated irradiated control. The greatest reduction in MPCE was observed for 250 mg/kg body weight AME, accompanied by the highest polychromatic erythrocyte to normochromatic erythrocyte ratio, in comparison with the non-drug-treated irradiated control. Therefore, further studies were carried out using this dose of AME, where the animals were administered with 250 mg/kg body weight of AME before exposure to 0, 0.5, 1, 2, 3 and 4 Gy of gamma-radiation and evaluated at 12, 24, 36 and 48 hours post-irradiation. Whole body irradiation of mice to different doses of gamma-radiation resulted in a dose-dependent increase in the frequency of MPCE at all post-irradiation times. Treatment of 250 mg/kg AME orally (p.o.) before irradiation significantly reduced the frequency of MPCE at all post-treatment times. The frequency of MPCE increased with time, reached a peak level at 24 hours, and declined thereafter. The occurrence of MNCE has also shown a pattern similar to MPCE, except that the MNCE frequency reached a peak level by 48 hours. The AME significantly reduced the frequency of MNCE at all post-irradiation times, when compared to the non-drug-treated irradiated group. Treatment of mice with AME before exposure to different doses of gamma-radiation resulted in the inhibition of a radiation-induced decline in the PCE/NCE ratio, when compared with the concurrent irradiated controls. To gain insight into the mechanism of action, AME was tested for its antioxidant effects in cell-free chemical systems using H2O2/FeSO4 to generate hydroxyl (*OH) radicals, which were measured by a fluorescent probe, 2V, 7V-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to generate superoxide (O2*-) anion radical, which was measured by a fluorescent probe dihydroethidium (DHE). AME significantly reduced fluorescence in a concentration dependent manner, indicating its efficacy to scavenge free radicals. Our results demonstrate that one of the mechanism of reduction in the radiation-induced DNA damage in mice bone marrow by AME may be due to scavenging of free radicals and elevation in the antioxidant status, as previously reported.

This chapter gives an overview of the radioprotective and radiosensitizing effect of curcumin. Ionizing radiations interact with biological molecules inducing radiolytic products like e(aq), *OH, *H, -OH, +H, O2, and peroxides. These free radicals damage important biomolecules and subsequently inflict deleterious effects in the organism. Whole-body exposure to ionizing radiations results in central nervous system, gastrointestinal tract, and bone marrow syndromes, whereas chronic irradiation causes cancer, birth anomalies, erythema, and dysfunctions to almost all organ of the body depending on the total dose and site of irradiation. Curcumin (diferuloyl methane), a yellow pigment present in the rhizomes of turmeric, has been used in Southeast Asia to give yellow color and flavor to curries. Turmeric has been used to treat various ailments in the Ayurvedic system of medicine in India. Recently, it has been evaluated for its radioprotective and radiosensitizing activities. Curcumin has been found to exert a dual mode of action after irradiation depending on its dose. It has been reported to protect various study systems against the deleterious effects induced by ionizing radiation and to enhance the effect of radiation. Therefore, curcumin can be very useful during radiotherapy of cancer. Administration of curcumin in patients will be able to kill the tumor cells effectively by enhancing the effect of radiation and, at the same time, protect normal cells against the harmful effects of radiation. The available information on curcumin suggests that the radioprotective effect might be mainly due to its ability to reduce oxidative stress and inhibit transcription of genes related to oxidative stress and inflammatory responses, whereas the radiosensitive activity might be due the upregulation of genes responsible for cell death.

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. Traditionally known for its an antiinflammatory effects, curcumin has been shown in the last two decades to be a potent immunomodulatory agent that can modulate the activation of T cells, B cells, macrophages, neutrophils, natural killer cells, and dendritic cells. Curcumin can also downregulate the expression of various proinflammatory cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most likely through inactivation of the transcription factor NF-kappaB. Interestingly, however, curcumin at low doses can also enhance antibody responses. This suggests that curcumin's reported beneficial effects in arthritis, allergy, asthma, atherosclerosis, heart disease, Alzheimer's disease, diabetes, and cancer might be due in part to its ability to modulate the immune system. Together, these findings warrant further consideration of curcumin as a therapy for immune disorders.

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Purpose: Methylation of H3 at lysine 4 (H3 Lys4) may be correlated with active gene trascription, whereas methylation of H3 at lysine 9 (H3 Lys9) may be linked to gene repression in murine cells and Schizosaccharomyces pombe., Methods: Using Western blot analysis, heat-induced changes were studied in two human oral cancer cell lines, HSC4 (thermoresistant cells) and KB (thermosensitive cells). Histone H3 changes were studied; in particular for H3-Lys4 and H3-Lys9 methylation combined with KNK437., Results: Heating of HSC4 cells at 45 degrees C for 20 min and KB cells for 3 min gradually increased H3-Lys4 and H3-Lys9 methylation. Treatment of both cells with 100 microM KNK437 before or after heat-treatment inhibited methylation of H3-Lys4, while methylation of H3 Lys9 remained unaffected. Use of KNK437 either before or after heat treatment inhibited the expression of HSP70., Conclusions: The findings suggest that heat-induced methylation of histone H3 may be correlated with the induction of HSPs by heating.

Liv 52 is a mixture of botanicals that is used clinically to treat various hepatic disorders. In this study, the radioprotective activity of Liv 52 was evaluated in mice given whole-body exposure to different doses of gamma-radiation. In addition, a series of studies was conducted to explore the mechanism of radioprotection. Radioprotection was evaluated by the ability of Liv 52 to reduce both the frequency of bone marrow micronucleated erythrocytes and the lethality produced by (60)Co gamma-radiation. Mice were treated by oral gavage once daily for seven consecutive days with 500 mg/kg body weight Liv 52 or carboxymethylcellulose vehicle prior to radiation. Micronucleated polychromatic erythrocytes (MPCEs), micronucleated normochromatic erythrocytes (MNCEs), and the PCE/NCE ratio were measured at 0.25-14 days after exposure to whole-body radiation doses of 0, 0.5, 1.5, 3.0, or 4.5 Gy; animal survival was monitored after doses of 7, 8, 9, 10, 11, or 12 Gy. Pretreatment of mice with Liv 52 significantly reduced the frequency of radiation-induced MPCEs and MNCEs. Irradiation reduced the PCE/NCE ratio in a dose-related manner for up to 7 days following irradiation; Liv 52 pretreatment significantly mitigated against these reductions. Liv 52 treatment also reduced the symptoms of radiation sickness and increased mouse survival 10 and 30 days after irradiation. Liv 52 pretreatment elevated the levels of reduced glutathione (GSH), increased the activities of glutathione transferase, GSH peroxidase, GSH reductase, superoxide dismutase, and catalase, and lowered lipid peroxidation (LPx) and the activities of alanine amino transferase and aspartate aminotransferase 30 min after exposure to 7 Gy of gamma-radiation. Liv 52 pretreatment also reduced radiation-induced LPx and increased GSH concentration 31 days following the exposure. The results of this study indicate that pretreatment with Liv 52 reduces the genotoxic and lethal effects of gamma-irradiation in mice and suggest that this radioprotection may be afforded by reducing the toxic effects of the oxidative products of irradiation.

Coleus aromaticus (Benth, Family: Laminaceae), Indian Oregano native to India and Mediterranean, is well known for its medicinal properties. A preliminary study was undertaken to elucidate in vitro free radical scavenging potential and inhibition of lipid peroxidation by C.aromaticus hydroalcoholic extract (CAE). Anti-clastogenic and radioprotective potential of CAE were studied using micronucleus assay after irradiating Chinese hamster fibroblast (V79) cells. CAE at 10, 20, 40, 60, 80, 100 and 120 mug/ml resulted in a dose-dependent increase in radical scavenging ability against various free radicals viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide anion (O(2)(*-)), hydroxyl (OH(*)) and nitric oxide (NO(*)) generated in vitro. A maximum scavenging potential was noticed at 100 mug/ml and a saturation point was reached thereafter with the increasing doses of CAE. The free radical scavenging potential of the extract was in the order of DPPH > ABTS > Superoxide > Hydroxyl > Nitric oxide. CAE also exhibited a moderate inhibition of lipid peroxidation in vitro, with a maximum inhibition at 60 mug/ml (33%), attaining saturation at higher doses. The extract also rendered protection against radiation induced DNA damage, as evidenced by the significant (P < 0.05) decrease in the percentage of radiation-induced micronucleated cells (MN) and frequency of micronuclei (total). A maximum anticlastogneic effect/ radioprotection was noticed at a very low concentration i.e., 5 mug/ml of CAE, treated 1 h prior to 2 Gy of gamma radiation. A significant (P < 0.0001) anticlastogenic/radioprotective effect was also observed when the cells were treated with an optimum dose of CAE (5 mug/ml) 1 h prior to 0.5, 1, 2 and 4 Gy of gamma radiation compared with the respective radiation control groups. Overall, our results established an efficient antioxidant, anticlastogenic and radioprotective potential of CAE, which may be of great pharmacological importance.

Extracts of Tinospora cordifolia (TCE) have been shown to possess anti-tumor properties, but the mechanism of the anti-tumor function of TCE is poorly understood. This investigation elucidates the possible mechanism underlying the cytotoxic effects of dichlormethane extracts of TCE, after selecting optimal duration and concentration for treatment. HeLa cells were exposed to various concentrations of TCE, which has resulted in a concentration-dependent decline in the clonogenicity, glutathione-S-transferase (GST) activity and a concentration-dependent increase in lipid peroxidation (TBARS) with a peak at 4 h and lactate dehydrogenase (LDH) release with a peak at 2 h. Our results suggest that the cytotoxic effect of TCE may be due to lipid peroxidation and release of LDH and decline in GST.

Purpose: Normal tissue radiosensitivity is the major limiting factor in radiotherapy of cancer. The use of phytochemicals may reduce the adverse effects of radiation in normal tissue. The effect of ethyl acetate fraction of Aphanamixis polystachya (EAP) was investigated on the radiation-induced chromosome damage in the bone marrow cells of Swiss albino mice exposed to various doses of gamma-radiation., Materials and Methods: The mice were divided into two groups, one group was exposed to 0, 1, 2, 3, 4 or 5 Gy of gamma-radiation, while another group received 7.5 mg/kg body weight (BW) of EAP 1 h before exposure to 0, 1, 2, 3, 4 or 5 Gy of gamma-radiation. Various asymmetrical chromosome aberrations were studied in the bone marrow cells of mice at 12, 24 or 48 h post-irradiation. To understand the mechanism of action of the free radical scavenging activity of 0, 5, 10, 20, 30, 40, 50, 60 or 70 microg/ml EAP, assays were carried out in vitro., Results: Irradiation of mice to different doses of gamma radiation caused a dose dependent elevation in the frequency of aberrant cells and chromosome aberrations like chromatid breaks, chromosome breaks, dicentrics, acentric fragments and total aberrations at all the post-irradiation times studied. The maximum asymmetrical aberrations were scored at 24 h post-irradiation except chromatid breaks that were highest at 12 h post-irradiation. A maximum number of polyploid and severely damaged cells (SDC) were recorded at 24 h post-irradiation in the SPS+irradiation group. Treatment of mice with 7.5 mg/kg BW of EAP before exposure to 1-5 Gy of whole body gamma-radiation significantly reduced the frequencies of aberrant cells and chromosomal aberrations like acentric fragments, chromatid and chromosome breaks, centric rings, dicentrics and total aberrations at all post-irradiation scoring times (p<0.01). The EAP showed a concentration dependent scavenging of hydroxyl, superoxide, 2,2'-diphenyl-1-picryl hydrazyl (DPPH) radicals and the 2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid (ABTS) cation radicals in vitro. EAP treatment also reduced lipid peroxidation in bone marrow cells in a concentration dependent manner., Conclusion: Our study demonstrates that EAP protects mouse bone marrow cells against radiation-induced chromosomal aberrations and this reduction in radiation-induced chromosome damage may be due to free radical scavenging and reduction in lipid peroxidation. The radioprotection by EAP is best comparable to that of protection demonstrated by the grape fruit flavonone, naringin, in our earlier studies in mouse bone marrow cells.

The anticancer activity of dichloromethane extract of guduchi [Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Family: Menispermaceae (TCE)] in the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC mice receiving 25, 30, 40, 50 and 100 mg/kg, TCE showed a dose dependent elevation in tumor-free survival and a highest number of survivors were observed at 50 mg/kg TCE, which was considered as an optimum dose for its neoplastic action. The average survival time (AST) and median survival time (MST) for this dose were approximately 56 and 55 d, respectively when compared with 19 d of non-drug treated controls. Administration of 50 mg/kg TCE resulted in 100% long-term survivors (up to 90 d). An attempt was also made to evaluate the effectiveness of TCE in the various stages of tumor development, where 50 mg/kg TCE was administered intraperitoneally after 1, 3, 6, 9, 12 or 15 d of tumor inoculation and these days have been arbitrarily designated as stage I, II, III, IV or V, respectively for reasons of clarity. The greatest anticancer activity was recorded for stage I, II and III where number of long term survivors (LTS) was approximately 33, 25 and 17%, respectively. However, treatment of mice at stage IV and V did not increase LTS, despite an increase in AST and MST. The EAC mice receiving 50 mg/kg TCE showed a time dependent depletion in the glutathione (GSH) activity up to 12 h post-treatment and marginal elevation thereafter. This depletion in GSH was accompanied by a drastic elevation in lipid peroxidation (LPx) and a maximum elevation in LPx was observed at 6 h that declined gradually thereafter. TCE exerted cytotoxic effect on tumor cells by reducing the GSH concentration and increase in LPx simultaneously.

Objective: The present in vitro study has been designed to establish and compare the effects of citric acid, EDTA, and tetracycline HCl on human periodontally diseased roots on the structure, attachment, and orientation of V79 (primary Chinese hamster lung fibroblasts) cells and human periodontal ligament fibroblasts (HPDL)., Materials and Methods: Commercially available V79 cells and HPDL derived from healthy human third molars were used in this study. These fibroblasts were left in solution for seven days in order to attain confluence. Forty single-rooted teeth were obtained from patients diagnosed with periodontitis. The crown part was removed under constant irrigation and the root was split vertically into two equal halves, thus, yielding 80 specimens. Following scaling and root planing, the specimens were washed with phosphate buffered saline (PBS) and kept in 50 microg/ml gentamycin sulphate solution for 24 hours. The root pieces were then treated as follows: citric acid at pH 1, 24% EDTA, or with a 10% solution of tetracycline HCl and were then placed in V79 fibroblast cultures and HPDL cultures. The specimens were harvested after four weeks and were fixed in 2.5% glutaraldehyde in PBS before preparation for scanning electron microscopy (SEM)., Results: The behavior of V79 cells was similar to that of human periodontal ligament cells on root conditioned surfaces. V79 and HPDL showed a healthy morphology on root surfaces treated with citric acid and EDTA and a relatively unhealthy appearance on root surfaces treated with tetracycline HCl and distilled water (control group)., Conclusion: The results suggest the use of citric acid and EDTA as root conditioning agents favorably affects the migration, attachment, and morphology of fibroblasts on human root surfaces, which may play a significant role in periodontal healing and regeneration.

The anticancer effect of various doses of an alkaloid fraction of Sapthaparna, Alstonia scholaris (ASERS), was studied in vitro in cultured human neoplastic cell lines (HeLa, HepG(2), HL60, KB and MCF-7) and in Ehrlich ascites carcinoma bearing mice. Treatment of HeLa cells with 25 microg/mL ASERS resulted in a time dependent increase in the antineoplastic activity and the greatest activity was observed when the cells were exposed to ASERS for 24 h. However, exposure of cells to ASERS for 4 h resulted in 25% viable cells and hence this time interval was considered to be the optimum time for treatment and further studies were carried out using this time. Treatment of various cells with ASERS resulted in a concentration dependent decline in the viable cells and a nadir was reached at 200 microg/mL in all the cell lines studied. The IC50 was found to be 5.53, 25, 11.16, 10 and 29.76 microg/mL for HeLa, HePG2, HL60, KB and MCF-7 cells, respectively. Similarly, administration of ASERS, once daily for 9 consecutive days to the tumor bearing mice caused a dose dependent remission of the tumor up to 240 mg/kg body weight, where the greatest antitumor effect was observed. Since 240 mg/kg ASERS showed toxic manifestations, the next lower dose of 210 mg/kg was considered as the best effective dose, in which 20% of the animals survived up to 120 days post-tumor-cell inoculation as against no survivors in the saline treated control group. The ASERS treatment resulted in a dose dependent elevation in the median survival time (MST) and the average survival time (AST) up to 240 mg/kg ASERS and declined thereafter. The surviving animals were healthy and disease free. The effect of ASERS was better than cyclophosphamide, which was used as a positive control, where all the animals succumbed to death by 40 days and the MST and AST were 19.5 and 18.3 days, respectively. The effective dose of 210 mg of ASERS was 3/10 of the LD50 dose, which increased the MST and AST up to 54 and 49.5 days, respectively., (Copyright 2006 John Wiley & Sons, Ltd.)

The radioprotective effect of bael (Aegle marmelos, AME) extract was studied in Swiss albino mice against radiation-induced changes in the peripheral blood, spleen colony forming units, and intestinal mucosa. The mice were treated with 250 mg/kg body weight of AME orally once daily for five consecutive days before exposure to an acute dose of 7 Gy of gamma radiation after the last administration. The peripheral blood was collected and evaluated for red blood cell (RBC), hemoglobin, total leukocyte count (TLC), and lymphocyte count on days one and seven postirradiation. The nucleated bone marrow cells were isolated and tested for colony-forming units (CFUs) in spleen at days one and seven. AME protected mice against the radiation-induced decline in hemoglobin, total leukocyte, and lymphocytes counts and the clonogenicity of hemopoietic progenitor cells assessed by the exogenous spleen colony-forming assay. Irradiation of mice caused a significant decline in the villus height and crypt number with an increase in goblet and dead cells in the small intestine, where the maximum changes were observed on day one postirradiation, indicating a severe damage, and signs of recovery at day seven postirradiation. Treatment of mice with AME before irradiation elevated the peripheral cell count as well as villus height and the crypt number accompanied by a decline in goblet and dead cells when compared with the irradiation control. The recovery and regeneration were faster in AME pretreated animals than the irradiation alone. AME pretreatment significantly decreased lipid peroxidation accompanied by a significant elevation in the GSH concentration in the mouse intestine. The data clearly indicate that the AME significantly reduced the deleterious effect of radiation in the intestine and bone marrow of mouse and could be a useful agent in reducing the side effects of therapeutic radiation.

Objective: Various studies have shown that the root surface condition may play an important role in wound healing. Root surface demineralization has been shown to promote the establishment of new connective tissue attachment. Various agents, including citric acid, ethylenediaminetetraacetic acid (EDTA), and tetracycline, have been used to try to achieve a root surface that is biocompatible with the adjacent periodontal cells. Traditional in vitro studies have used periodontal ligament fibroblasts and scanning electron microscopic studies to check the efficacy of these root-conditioning agents. The objective of this study was to assess the efficacy of trypan blue to evaluate fibroblast attachment in an in vitro model using V79 fibroblasts (embryonic Chinese hamster lung fibroblasts) on root specimens treated by citric acid, EDTA, and tetracycline., Method and Materials: Citric acid-, EDTA-, and tetracycline-treated root specimens were placed in cultures of V79 cells and in human periodontal ligament cells, which acted as a control. The treated root specimens were removed from the cultures after 4 weeks and immediately treated with 1% trypan blue. Trypan blue was selected because it can stain only nonvital tissues., Results: The root specimens placed in V79 and human periodontal ligament cultures showed unstained areas, indicating the presence of vital cells, in contrast to the stained areas, which represented the areas devoid of cells., Conclusion: This in vitro screening model based on the trypan blue exclusion principle may be used for immediate evaluation of the efficacy of various root-conditioning agents. V79 cells may be used as an alternative to human periodontal ligament fibroblasts in the evaluation of the efficacy of root conditioning agents.

The cytotoxic effect of various concentrations of echitamine chloride was studied in HeLa, HepG2, HL60, KB and MCF-7 cell lines in-vitro and in mice bearing Ehrlich ascites carcinoma (EAC). Exposure of various cells to different concentrations of echitamine chloride resulted in a concentration-dependent cell killing, and KB cells were found to be most sensitive amongst all the cells evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mg kg-1 echitamine chloride showed a dose-dependent elevation in the anti-tumour activity, as evident by increased number of survivors in comparison with the non-drug treated controls. The highest dose of echitamine chloride (16 mg kg-1) caused toxicity in the recipient mice, therefore 12 mg kg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mg kg-1 echitamine chloride resulted in an increase in the median survival time (MST) up to 30.5 days, which was 11.5 days higher than the non-drug treated control (19 days). Administration of 16 mg kg-1 echitamine chloride to EAC mice resulted in a time dependent elevation in lipid peroxidation that reached a peak at 6 h post-treatment, whereas glutathione concentration declined in a time dependent manner and a maximum decline was reported at 3 h post-treatment. Our study demonstrated that echitamine chloride possessed anti-tumour activity in-vitro and in-vivo.

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., (Copyright 2005 John Wiley & Sons, Ltd.)

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.

Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 microg/ml of MGN for 30 min before exposure to 3 Gy of (60)Co gamma-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 microg/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 microg/ml MGN. Since the lowest MNBNC frequency was observed for 50 microg/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of gamma-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 microg/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 micro/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of (.)OH (hydroxyl), O(2) (.-) (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS(.+) (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals., ((c) 2005 Wiley-Liss, Inc.)

The radioprotective effects of various concentrations (0, 0.25, 0.5, 1, 2, 5, 10, 17.5, 25, 50, 75 and 100 mg/kg b.wt.) of mangiferin (MGN) was studied in the DBAxC57BL mice whole body exposed to 10 Gy of gamma-irradiation. Treatment of mice with different doses of MGN, one hour before irradiation reduced the symptoms of radiation sickness and delayed the onset of mortality when compared with the non-drug treated irradiated controls. The radioprotective action of MGN increased in a dose dependent manner up to 2mg/kg and declined thereafter. The highest radioprotective effect was observed at 2mg/kg MGN, where greatest number of animals survived against the radiation-induced mortality. The administration of 0.5, 1, 2, 5, 10 and 17.5 mg/kg MGN reduced the radiation-induced gastrointestinal death as evident by a greater number of survivors up to 10 days in this group when compared with the DDW + 10 Gy irradiation group. A similar effect of MGN was observed for the radiation-induced bone marrow deaths also. Our study demonstrates that mangiferin, a gluosylxanthone, present in the Mangifera indica protected mice against the radiation-induced sickness and mortality and the optimum protective dose of 2mg/kg was 1/200 of LD50 dose (400 mg/kg) of MGN. The administration of 400 mg/kg MGN induced 50% mortality, therefore LD50 of the drug was considered to be 400 mg/kg.

The radioprotective activity of the hydroalcoholic extract of jamun seeds (SCE) was studied in mice exposed to different doses of gamma radiation. The mice were injected with 0, 5, 10, 20, 40, 60, 80, 100, 120, 140 or 160 mg/kg body weight of SCE, before exposure to 10 Gy of gamma radiation, to select the optimum dose of radiation protection. The 80 mg/kg SCE was found to offer highest protection, therefore, further studies were carried out using this dose. The drug was more effective when administered through the intraperitoneal route at equimolar doses than the oral route. Since higher survival was observed for the i.p. route (50%), than the oral route (29.2%), all other studies were carried out by injecting SCE intraperitoneally. The mice treated with 80 mg/kg body weight SCE intraperitoneally before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation showed reduction in the symptoms of radiation sickness and mortality at all exposure doses and caused a significant increase in the animal survival when compared with the concurrent double distilled water (DDW) + irradiation group. The SCE treatment protected mice against the gastrointestinal as well as bone marrow deaths and the DRF was found to be 1.24.

Hemibody irradiation in multiple fractionated doses is frequently used for the treatment of various neoplastic disorders. It produces both acute and late effects on the skin and subcutaneous tissues that have profound implications in the healing of surgical wounds. Because of the crucial practical importance of hemibody radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective herbal products in the reconstruction of irradiated wounds. Therefore, the effect of pretreatment of curcumin was studied on the healing of excision wound in mice exposed to 2, 4, 6, or 8 Gy of hemibody gamma-radiation. A full-thickness skin wound was created by removing the skin flap of the dorsum of 8- to 10-week-old Swiss albino mice partially (lower half, below the rib cage) exposed to 2, 4, 6, or 8 Gy of gamma-radiation. The progression of wound contraction was monitored periodically by capturing video images of the wound, where the first image of each wound from different groups was obtained 1 day after wounding and that day was considered as day 0. Eight animals were used in each group at each exposure dose for wound contraction studies. Furthermore, the effect of curcumin on mean healing time after exposure of mice to 2, 4, 6, or 8Gy of hemibody gamma-radiation was also evaluated, where eight animals were used in each group at each exposure dose. Collagen, hexosamine, DNA, nitric oxide, and histologic profiles were also evaluated during the course of healing of excision wounds at days 4, 8, and 12 after irradiation treated or not with curcumin before exposure to 0 or 6 Gy of gamma-radiation. Six animals were used in each group at each interval for each biochemical parameter studied, except for histologic evaluations, where four animals were used in each group at each interval. Exposure of mice to different doses of gamma-radiation resulted in a dose-dependent delay in contraction and wound-healing time of excision wound, whereas curcumin pretreatment caused a significant elevation in the rate of wound contraction and a decrease in the mean wound-healing time. Treatment with curcumin before irradiation enhanced the synthesis of collagen, hexosamine, DNA, nitrite, and nitrate, and histologic assessment of wound biopsy specimens revealed improved collagen deposition and an increase in fibroblast and vascular densities. The authors' study demonstrates that curcumin pretreatment has a conducive effect on the irradiated wound and could be a substantial therapeutic strategy for ameliorating radiation-induced delay in wound repair in cases of radiation-induced skin injuries.

In order to evaluate the seasonal variation as well as cytotoxicity of different fractions of Alstonia scholaris R. Br. (ASE), the HeLa cells were treated with different doses of various fractions of ASE collected in monsoon, winter and summer. The exposure of HeLa cells to different extracts prepared from the stem bark collected in monsoon, winter and summer seasons resulted in a dose dependent increase in the cell killing effect of ASE and the highest cell killing effect was observed for the extract prepared from the summer collections. Similarly, treatment of HeLa cells with different doses of various fractions of the Alstonia scholaris extract viz. residue (ASERS), steroidal (ASEST), chloroform (ASECH), petroleum ether (ASEPE), diethyl ether (ASEDE), ethyl acetate (ASEEA), n-butanol (ASENB), aqueous (ASEAQ) and echitamine chloride (ECL) also resulted in a dose dependent decline in the cell viability, where the greatest cytotoxic effect was observed for residue (ASERS), followed by the whole extract (ASE) and chloroform (ASECH) fraction, while the least activity was observed for the steroidal (ASEST) fraction. The cytotoxicity declined ASERS > ASE > ASECH >ECL > ASEEA > ASEDE > ASEPE > ASENB > ASEAQ > ASEST in order. Our study demonstrates that the extract prepared from the summer collection, and the fractions containing the alkaloids were highly effective in cell killing. The extract of ASE was more powerful than the active principle echitamine present in ASE.

The effect of radiation on tumor tissue can be optimized by adding radiosensitizing agents, in order to achieve a greater degree of tumor damage than expected from the use of either treatment alone. The ethanolic extract of Aphanamixis polystachya (APE) was tested in Swiss albino mice transplanted with Ehrlich ascites carcinoma (EAC) and exposed to various doses of gamma-radiation. EAC mice received 0, 10, 25, 50, 75, 100, 150 or 200 mg/kg body wt APE before exposure to 6 Gy gamma-radiation followed by once daily administration for another 8 consecutive days post-irradiation. The optimum radiosensitizing dose was found to be 50 mg/kg APE that was further tested in EAC mice exposed to 0, 1, 2, 4, 6 or 8 Gy hemi body gamma-radiation. The best effect of APE and radiation was observed for 6 Gy gamma-radiation. The splitting of 50 mg into two equal fractions of 25 mg and administering the split dose with a gap of 8 h on 1, 3, 5, 7 or 9 d of tumor inoculation resulted in an increased survival even when the drug was administered at late stages (day 5) of tumor development. The APE treatment before irradiation elevated lipid peroxidation followed by a reduction in the glutathione contents. Treatment of tumor bearing mice with APE before irradiation further reduced the activities of various antioxidant enzymes like glutathione peroxidase, glutathione-s-transferase, superoxide dismutase and catalase at different post last drug administration (PLDA) times.

The radioprotective effect of an extract of Aegle marmelos (L.) Correa (AME), family Rutaceae, was investigated in mice exposed to different doses of gamma-radiation. Mice were administered orally AME 250 mg/kg b.wt. orally daily for 5 consecutive days before exposure to 6, 7, 8, 9, 10, or 11 Gy of gamma-radiation. The animals were monitored daily up to 30 days after irradiation for the development of symptoms of radiation sickness or death. Treatment of mice with AME before irradiation reduced the symptoms of radiation sickness and delayed death compared to the irradiated controls given sterile physiological saline (SPS). AME provided protection against both gastrointestinal and hematopoietic toxicities. Reducing the administration schedule of AME to 1 or 3 consecutive days or increasing the schedule to 7 consecutive days was not as effective as 5 consecutive days of preradiation schedule. The administration of AME after irradiation was not effective, and no survivors could be reported 30 days after irradiation. The LD50/30 was found to be 8.1 Gy for the SPS + irradiation group and 9.7 Gy for the AME + irradiation group. The oral administration of AME resulted in an increase in radiation tolerance by 1.6 Gy, and the dose reduction factor was found to be 1.2. Preradiation treatment of mice with AME caused a significant depletion in lipid peroxidation followed by a significant elevation in glutathione concentration in the liver of mice 31 days after irradiation. The drug was nontoxic up to a dose of 6000 mg/kg b.wt., the highest drug dose that could be tested for acute toxicity.

The anticancer effect of hydroalcoholic extract of Aegle marmelos (AME) was studied in the Ehrlich ascites carcinoma bearing Swiss albino mice. The spatial effect of various AME administration schedules showed that six-day administration increased the survival of tumor bearing mice. The best antineoplastic action of AME was obtained when AME administered through intraperitoneal route than the oral route at equimolar dose. Administration of AME once daily for six consecutive days to the tumor bearing mice caused a dose dependent remission of the tumor at 400 mg/kg body weight, where the greatest antitumor effect was observed and the higher doses showed toxic manifestations. A 24-d lengthening in life span was observed in EAC animals treated with 400 mg/kg AME. This dose of 400 mg/kg was considered as the best dose, where the animals survived up to 43 d post-tumor-cell inoculation as against no survivors in the saline treated control group. The antitumor activity when tested for different schedules for triple administrations, the best effect was observed for 1-2-3, followed by 1-3-5 and 1-5-9 days, respectively. Stage specific evaluation of AME inhibited the increase in body weight gain in animals due to tumor development during early stages only. The AME treatment resulted in a dose dependent elevation in the median survival time (MST) and average survival time (AST) up to 400 mg/kg AME and decline thereafter. The effective dose of 400 mg of AME is 1/6th of the LD50 dose, which increased the MST and AST up to 29 and 27 d, respectively. The acute toxicity study of AME showed that the drug was non-toxic up to a dose of 1750 mg/kg b. wt. The LD10 and LD50 was found to be 2000 and 2250 mg/kg.

The radioprotective effect of a hydroalcoholic extracted material from the fruit of Aegle marmelos (AME) was studied in mice exposed to different doses of gamma 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 gamma 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 gamma 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.

Effects of 20 mg/kg body weight of abana (ABE) on radiation-induced sickness and mortality in mice exposed to 7 Gy to 12 Gy of gamma irradiation were studied. Treatment of mice with abana 1 h before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls (double distilled water, DDW). Abana provided protection against both the gastrointestinal and haemopoietic deaths. However, animals of both the ABE+irradiation and DDW+irradiation groups did not survive up to 30 days post-irradiation beyond 11 Gy irradiation. The LD(50/30) was found to be 8.5 Gy for the DDW+irradiation group and 10.3 Gy for ABE+irradiation group. The administration of abana resulted in an increase in radiation tolerance by 1.8 Gy, and the dose modification factor (DMF) was found to be 1.2. The irradiation of animals resulted in a dose dependent elevation in lipid peroxidation, and a reduction in glutathione (GSH) concentration on day 31 post-irradiation. Treatment of mice with abana before irradiation caused a significant depletion in lipid peroxidation followed by a significant elevation in GSH concentration in the liver of mice at day 31 post-irradiation. Abana scavenged (*)OH, DPPH, ABTS(*+) and NO(*) in a concentration dependent manner in vitro. Our results indicate that the radioprotective activity of abana may be due to free radical scavenging and increased GSH level in irradiated mice.

The effects of 10 mg/kg of triphala extract (TE) was studied on radiation-induced sickness and mortality in mice exposed to 7-12 Gray (Gy) of gamma-irradiation. Treatment of mice with triphala once daily for 5 consecutive days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug double distilled water treated irradiated controls (DDW). Triphala provided protection against both gastrointestinal and hemopoetic death. However, animals of both the TE + irradiation and DDW + irradiation groups did not survive up to 30 days post-irradiation beyond 11 Gy irradiation. The LD50/30 was found to be 8.6 Gy for the DDW + irradiation group and 9.9 Gy for TE + irradiation group. The administration of triphala resulted in an increase in the radiation tolerance by 1.4 Gy, and the dose reduction factor was found to be 1.15. To understand the mechanism of action of triphala, the free radical scavenging activity of the drug was evaluated. Triphala was found to scavenge (.)OH, O(2) (.) 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) diammonium salt (ABTS)(.+) and NO(.) radicals in a dose dependent manner.

The plant extracts of 17 commonly used Indian medicinal plants were examined for their possible regulatory effect on nitric oxide (NO) levels using sodium nitroprusside as an NO donor in vitro. Most of the plant extracts tested demonstrated direct scavenging of NO and exhibited significant activity. The potency of scavenging activity was in the following order: Alstonia scholaris > Cynodon dactylon > Morinda citrifolia > Tylophora indica > Tectona grandis > Aegle marmelos (leaf) > Momordica charantia > Phyllanthus niruri > Ocimum sanctum > Tinospora cordifolia (hexane extract) = Coleus ambonicus > Vitex negundo (alcoholic) > T. cordifolia (dichloromethane extract) > T. cordifolia (methanol extract) > Ipomoea digitata > V. negundo (aqueous) > Boerhaavia diffusa > Eugenia jambolana (seed) > T. cordifolia (aqueous extract) > V. negundo (dichloromethane/methanol extract) > Gingko biloba > Picrorrhiza kurroa > A. marmelos (fruit) > Santalum album > E. jambolana (leaf). All the extracts evaluated exhibited a dose-dependent NO scavenging activity. The A. scholaris bark showed its greatest NO scavenging effect of 81.86% at 250 microg/mL, as compared with G. biloba, where 54.9% scavenging was observed at a similar concentration. The present results suggest that these medicinal plants might be potent and novel therapeutic agents for scavenging of NO and the regulation of pathological conditions caused by excessive generation of NO and its oxidation product, peroxynitrite.

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 effect of various doses (5, 10, 20, 40, 60, 80, 100, 120, 140 and 160 mg/kg b. wt.) of 50% ethanolic extract of Septilin (a herbal preparation) was studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma-irradiation. Treatment of mice with different doses of Septilin, consecutively for 5 days before irradiation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. All doses of Septilin provided protection against gastrointestinal (GI) deaths (death within 10 days of irradiation). However, the best protection was observed at 100 mg/kg b. wt. of Septilin, as the number of survivors after 30 days post-irradiation was highest (58.33%) in this group when compared with the other doses of Septilin. The number of survivors was 1.75 fold greater for 100 mg/kg Septilin when compared with the 2-mercaptopropionylglycine (MPG, 33.33%) which was used as a positive control. The LD(50) of Septilin was 1250 mg/kg as against the optimum protective dose of 100 mg/kg. Our study demonstrates Septilin as a good radioprotective agent., (Copyright (c) 2004 John Wiley & Sons, Ltd.)