Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100 mg/kg bw, administered intraperitoneally 30 min prior to 9.5 Gy whole-body γ-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50 mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100 mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50 mg/kg bw) in mice irradiated with 15 Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50 mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100 mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25 mg/kg bw.     

Free radical scavenging and radioprotective activity of dehydrozingerone against whole body gamma irradiation in Swiss albino mice

Dehydrozingerone (DZ) was explored for in vitro-in vivo antioxidant potential and in vivo radioprotective activity against whole body gamma irradiation in Swiss albino mice. DZ scavenged the ABTS (2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (1, 1-dipehnyl-2-picrylhydrazyl) free radicals at room temp. DZ reduced Fe (III) to Fe (II) at pH 7.4 and scavenged the NADH/phenazine methosulfate generated superoxide radical in cell free system. DZ also scavenged the nitric oxide radical generated by sodium nitroprusside. To evaluate the radioprotective activity, mice were exposed to whole body gamma irradiation 30 min after the drug treatment at a dose rate of 1.66 Gy/min. Pretreatment with DZ 75, 100 and 125 mg/kg, i.p. reduced the radiation induced mortality and increased the mean survival times (MSTs). An i.p. dose of DZ 100 mg/kg was found the most effective dose in preventing radiation sickness and increasing the MST. Pretreatment DZ100 mg/kg maintained the spleen index (spleen weight/body weight x 100) and stimulates the endogenous spleen colony forming units (CFU). Pretreatment with DZ100 mg/kg maintained the villus height close to normal, prevents mucosal erosion and basement membrane damage in irradiated mice jejunum. However, no significant reductions in dead, inflammatory and mitotic cells were observed in DZ pretreated mice, but there was an increased in crypt cells proliferation and regeneration. Pretreatment with DZ100 mg/kg significantly elevated the endogenous antioxidant enzymes (GSH, GST and SOD) in mice at 2, 4 and 8 h post sham irradiation. Radiation induced fall in endogenous antioxidant enzymes was significantly prevented by DZ pretreatment. Pretreatment with DZ 75 and 100 mg/kg reduced the radiation induced micronucleated polychromatic erythrocytes (MPCE) and normochromatic erythrocytes (MNCE) in mice bone marrow. DZ also maintained the polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratio (P/N ratio) in irradiated mice. Dose modifying factor (DMF) was calculated by using the graded radiation dose (8.0, 9.0, 9.5 and 10 Gy). DZ 100 mg/kg elevated radiation LD(50) from 9.1 to 10.0 Gy, indicating the DMF of 1.09.     

Radioprotective effects of ginsan,an immunomodulator

We previously reported that ginsan, a purified polysaccharide isolated from Panax ginseng, had a mitogenic activity, induced LAK cells, and increased levels of several cytokines. In an effort to identify other immunostimulatory effects, we evaluated the protective effects of ginsan injected in vivo against radiation by measuring its effects on the CFU-S bone marrow cells and spleen cells. Ginsan was found to significantly increase the number of bone marrow cells, spleen cells, granulocyte-macrophage colony-forming cells (GM-CFC), and circulating neutrophils, lymphocytes and platelets in irradiated mice. In addition, ginsan induced the endogenous production of cytokines such as Il1, Il6, Ifng and Il12, which are required for hematopoietic recovery, and was able to enhance Th1 function while interfering with the Th2 response in irradiated mice. We demonstrated that pretreatment with ginsan protected mice from the lethal effects of ionizing radiation more effectively than when it was given immediately after or at various times after irradiation. A significant increase in the LD(50/30) from 7.54 Gy for PBS injection to 10.93 Gy for mice pretreated with 100 mg/kg ginsan was observed. These findings indicate that ginsan may be a useful agent to reduce the time necessary for reconstituting hematopoietic cells after irradiation.     

Combined action of X-rays and nonylphenol on mouse sperm

The aim of this study was to assess the effects of 2-weeks’ X-ray and/or nonylphenol (NP) exposure on male mice’s sperm count and quality. Pzh:SFIS mice were exposed to X-rays (0.05 Gy, 0.10 Gy, 0.20 Gy) or to nonylphenol (25 mg/kg bw, 50 mg/kg bw, 100 mg/kg bw) or to both agents (0.05 Gy + 25 mg/kg bw NP, 0.10 Gy + 50 mg/kg bw NP). At 24 h and 5 weeks after the end of exposure the sperm count, morphology and frequency of DNA damage in the male germ cells were estimated. Each agent alone diminished sperm count and morphology. The dose of 0.05 Gy of X-rays decreased the frequency of DNA damage. Combined exposure to lower doses of both agents significantly improved sperm morphology and decreased the level of DNA damage compared to one agent alone. Combined exposure to higher doses reduced the frequency of DNA damage compared to the effect of the appropriate dose of NP. Results of combined exposure to low doses of both agents suggest that 0.05 Gy of X-rays stimulate the DNA damagecontrol system and in consequence repair of DNA caused by X-rays and NP. It may be correlated with increased antioxidant capacity.     

Differential radioprotection of tissues in C3H/J mice by a combination of 5-hydroxy L-tryptophan with 2-aminoethylisothiuronium bromide hydrobromide.

Differential radioprotection between normal tissues and carcinoma was observed in C3H/J mice treated with a combination of 5-hydroxy L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg). Protection to normal tissues was judged by LD50(30) and by radiation induced damage to bone marrow(BM) using clonogenic ability of blood forming stem cells (10 day CFUs) as the criteria. Pretreatment with 5-HTP + AET combination 30 min before whole body gamma radiation (WBGR) enhanced the recoveries of the number of blood forming stem cells in BM of irradiated mice after 0, 7th and 10th day of irradiation. LD50(30) for C3H/J mice was 7.3 Gy and the dose modifying factor (DMF) of 5-HTP + AET combination was 1.76. On the contrary, pretreatment with this combination did not protect the mammary carcinoma transplanted in C3H/J mice, when exposed to 80 Gy soft X-rays.     

Oral oxymetholone reduces mortality induced by gamma irradiation in mice through stimulation of hematopoietic cells

Oxymetholone is a 17α -alkylated anabolic-androgenic steroid. This drug can stimulate bone marrow cells and increase the blood cells in the peripheral blood vessels. It has been used for the treatment of anemia caused by low red cell production. Since oxymetholone has hematopoietic effect, we studied radioprotective effects of this drug in mice. In this study, we determined percentage of survival, dose-reduction factor (DRF) and hematological parameters in irradiated mice which treated with or without oxymetholone. Oxymetholone administrated at different doses 80, 160, 320, 640 mg/kg by gavages at 24 h before 8 Gy gamma irradiation. At 30 days after treatment, the following percentage of animals survival in each group was as: 80 mg/kg, 50%; 160 mg/kg, 50%; 320 mg/kg, 55%; 640 mg/kg, 75% and vehicle, 15%. Percentage of survival increased in all of treated groups statistically compared with irradiated-vehicle group. In the groups treated by oxymetholone, maximum protection was realized at 640 mg/kg. In order to calculate the DRF for oxymetholone, mice were exposed to whole-body gamma irradiation with dose ranges between 5.83 and 11.23 Gy. The probit line for oxymetholone-treated mice was shifted to the right with a DRF of 1.14. In mice exposed to whole-body gamma-irradiation (4 Gy), an oral administration of 640 mg/kg oxymetholone ameliorated radiation-induced decreases in circulating platelets and erythrocytes, but had a less effect on total number of WBC. These results demonstrate that oxymetholone stimulates myelopoiesis and thrombocytopenia and enhances survival in mice after ionizing radiation.     

Protective effect of sesamol against 60Co γ-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice

Abstract

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal (GI) systems is the rationale behind developing radioprotectors. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and GI injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through the intraperitoneal route and exposed to LD_50/30 (7.5 Gy) and sublethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100% against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells, T cell subpopulations, and splenocyte proliferation in the spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with a decrease of radiation-induced micronuclei (MN) and apoptosis in bone marrow and spleen, respectively. Sesamol pre-treatment inhibited lipid peroxidation, translocation of gut bacteria to spleen, liver, and kidney, and enhanced regeneration of crypt cells in the GI system. In addition, sesamol pre-treatment reduced the radiation-induced pattern of expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI. This reduction in apoptotic proteins was associated with the increased anti-apoptotic-Bcl-x and PCNA proteins. Further, assessment of antioxidant capacity using ABTS and DPPH assays revealed that sesamol treatment alleviated total antioxidant capacity in spleen and GI tissue. In conclusion, the results of the present study suggested that sesamol as a single prophylactic dose protects hematopoietic and GI systems against γ-radiation-induced injury in mice.     

Radioprotection by mangiferin in DBAxC57BL mice: a preliminary study

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.     

大豆提取物（CKBN）对免疫低下小鼠免疫功能的影响

目的观察大豆提取物（CKBN）对免疫低下小鼠免疫功能的影响。方法腹腔注射环磷酰胺（cyclophosphamide,CTX）建立免疫功能低下小鼠模型,观察1、25、50、100 mg/kg剂量CKBN对免疫低下小鼠免疫功能的影响。结果25 mg/kg组的CKBN可显著增加免疫低下小鼠的脾指数;25、50、100 mg/kg组均能明显抑制环磷酰胺对小鼠外周血白细胞数量的影响,1 mg/kg组可显著提高单核细胞百分率,50 mg/kg组可显著提高中性粒细胞百分率;100 mg/kg组的IgG2a水平高于环磷酰胺组;1、25、50 mg/kg可显著提高腹腔巨噬细胞的吞噬功能;25 mg/kg组可显著提高NK细胞杀伤活性。结论CKBN能显著增强CTX造成的免疫低下小鼠的免疫功能。     

Radioprotective effects of serum thymic factor in mice.

Serum thymic factor (FTS) reduced mortality of mice after total-body irradiation with 7.56 Gy X rays. The radioprotective effect was achieved by daily repeated subcutaneous injections of 3-100 micrograms FTS, while doses higher than 300 micrograms/day/mouse were neither radioprotective nor toxic. Similarly, degeneration of the spleen was moderated by 3-100 micrograms FTS but not by 500 micrograms FTS in sublethally (3.78 Gy) irradiated mice. Histological examination showed that hematopoiesis was enhanced in the spleen by daily injections of 10 micrograms FTS. Spleen cells from the FTS-treated mice incorporated more [3H]thymidine in culture with or without concanavalin A. The treatment with FTS increased the production of colony-stimulating factor in the spleen as well as in peritoneal macrophage-like cells, and caused a significant increase in the number of granulocyte-macrophage colony-forming cells both in the spleen and in the femoral bone marrow. Furthermore, FTS prevented a decrease in circulating neutrophils in the sublethally irradiated mice. Prominent overshoot recovery of myelopoiesis, which occurred occasionally in sublethally irradiated mice, did not occur in the FTS-treated mice. The decrease in blood erythrocytes was also significantly reduced. These observations imply that this thymic hormone has potential as a radioprotector.     

不同剂量博莱霉素诱导小鼠肺纤维化的差异及动态变化

目的探讨博来霉素诱导小鼠肺纤维化最佳剂量和方法。方法 126只8周龄雄性ICR小鼠,随机分成一次性大剂量模型和多次小剂量模型。一次性大剂量模型分为200 mg/(kg.bw)BLM组、150 mg/(kg.bw)BLM组、100 mg/(kg.bw)BLM组及阴性对照组(DN组),每组18只,分别经尾静脉一次性注射BLM 200、150、100mg/(kg.bw)及生理盐水10 mL/(kg.bw),各组分别于第7、14、21天各处死6只。多次小剂量模型分为每日10 mg/(kg.bw)BLM组及阴性对照组(N组),分别经尾静脉注射BLM 10 mg/(kg.bw)及生理盐水10 mL/(kg.bw),每天1次,连续注射14 d,两组分别于第14、21、28天各处死6只。留取肺组织,观察肺组织病理改变,检测Ⅲ型胶原的含量,观察小鼠体重及生存率。结果①在一次性大剂量模型中,BLM各剂量组肺泡炎症评分及肺纤维化评分与正常组相比,除100 mg/(kg.bw)BLM组和150 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P>0.05),其余各组差异均有显著性(P<0.05);各个剂量组Ⅲ型胶原的表达面积与正常组相比,除100 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P>0.05),其余各组均较正常组高(P<0.05),各个剂量组分别在第21天达到高峰,以200 mg/(kg.bw)BLM组第21天组Ⅲ型胶原的表达面积最高;该模型小鼠各剂量组死亡率为0。②在多次小剂量模型中,各组的肺泡炎症与肺纤维化程度与正常组相比差异均有显著性(P<0.05);各组Ⅲ型胶原的表达也均高于正常组(P<0.05),且随着时间的延长呈进行性增加,在第28天达到高峰;该模型小鼠共死亡11只,死亡率为30.56%。结论在本实验中,以尾静脉一次性注射BLM 200 mg/(kg.bw)后第21天诱导建立的ICR小鼠肺纤维化模型成模最好,其小鼠死亡率低,操作简单,有效安全方便的特点使之有希望成为一种复制肺纤维化的理想模型。     

Radioprotective properties of indralin combined with cystamine and mexamine

The radioprotective properties of indralin when it is used in combination with cystamine and mexamine are studied in inbred mice and rats. The mice and rats are irradiated with γ rays emitted by ⁶⁰Co at doses of 9.0 and 9.5 Gy, respectively. A combined parenteral administration of indralin and cystamine in mice at doses of 25 mg/kg each is revealed to potentiate the radioprotective properties of indralin up to a level close to the ED₅₀ effect, while the separate application of these drugs in doses of 25 mg/kg each has no or a very weak radioprotective effect. Indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally in rats are found to almost completely eliminate the animal mortality caused by gastrointestinal acute radiation syndrome; the mortality in the control radiation group reaches 60% on the seventh day after the animals have been exposed to radiation at a dose of 9.5 Gy. However, if bone-marrow acute radiation syndrome develops under the above condition of super-lethal dose, the radioprotectors have a low radioprotective effect. Under the this condition, the combined application of indralin and mexamine in the same doses has 50% of radioprotective effect reached by applying these radioprotectors separately in double doses.     

Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation

The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6-12 Gy of gamma radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 1/50 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in the lipid peroxidation and depletion of GSH on day 31 postirradiation; both effects were lessened by pretreatment with ZOE. ZOE also had a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and Candida albicans.     

The evaluation of the radioprotective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to γ-radiation

The effect of 0, 5, 6.25, 10, 12.5, 20, 25, 40, 50 and 80 mg/kg b. wt. of aqueous extract of triphala (an Ayurvedic herbal medicine) administrered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma-radiation. Treatment of mice with different doses of triphala consecutively for five days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. The highest protection against GI (gastrointestinal) death was observed for 12.5 mg/kg triphala, where a highest number of survivors were reported up to 10 days post-irradiation. While 10 mg/kg triphala i.p. provided the best protection as evidenced by the highest number of survivors after 30 days post-irradiation in this group when compared with the other doses of triphala. Toxicity study showed that triphala was non-toxic up to a dose of 240 mg/kg, where no drug-induced mortality was observed. The LD50 dose i.p. of triphala was found to be 280 mg/kg b. wt. Our study demonstrates the ability of triphala as a good radioprotective agent and the optimum protective dose of triphala was 1/28 of its LD50 dose.     

Antioxidant and radioprotective effect of the active fraction of Pilea microphylla (L.) ethanolic extract

The ethanolic extract of Pilea microphylla (L.) was defatted, successively fractionated with acetone and the residue so obtained was found to be most potent when subjected to detailed free radical scavenging and in vivo radioprotection studies. The most active fraction reacts with free radicals, such as DPPH (50 microM), ABTS(.)(-) (100 microM) and (.)OH (generated by Fenton reaction) with IC(50) value of 23.15 microg/ml, 3.0 microg/ml and 310 microg/ml, respectively. The most active fraction inhibited iron-induced lipid peroxidation in phosphatidyl choline liposomes with an IC(50) of 13.74 microg/ml. The kinetics of scavenging of DPPH and ABTS(.)(-) radicals were followed at different concentrations of the fraction by employing stopped-flow studies. The observed first order decay rate constants at 200 microg/ml and 50 microg/ml of fraction with DPPH (50 microM) and ABTS(.)(-) (50 microM) were found to be 0.4s(-1) and 2.1s(-1), respectively. The fraction when screened for in vivo radioprotection in Swiss albino mice showed 80% protection at a dose of 900 mg/kg and with a DRF of about 1.12. The fraction was also found to protect livers of irradiated mice from depletion of endogenous antioxidant enzymes like glutathione, GST, SOD, catalase and thiols. The fraction also protected the villi height, increased the number of crypt cells while offering general protection to the intestine from acute radiation effects. The fraction also protected the hematopoietic system as assessed by endogenous spleen colony assay, contributing to the overall radioprotective ability.     

Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice

Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further, the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However, in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments, total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pretreated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice.     

The radiation-modifying capacity of xenogenic apotransferrin for the number of endogenous colony forming units in the spleen of irradiated mice

After intraperitoneal injection of 100 or 198 mg/kg of human serum apotransferrin (apo TF) to mice 1 day before acute exposure to 6 Gy of gamma-radiation, the number of endogenous CFU in spleen (CFUs) increased 2.5 or 2.6 times respectively. At a dose fo 10 mg/kg of the protein only an increasing tendency was found, whereas a dose of 1 mg/kg was inefficient. A dose of 100 mg/kg of BSA did not show any effect suggesting that non-specific immune response to alien antigen did not contribute to apo TF radiomodifying action. The following mechanisms of the apoTF radiomodifying effect are discussed: 1) the ability of the protein to inactivate Fe3+ ions that reduces the consequences of radiation oxidative stress; 2) the stimulation of proliferation of the exposed bone marrow cells by activation of Fe3+ transport or by Ca2+ mediated mechanism of mitogen signal transduction; 3) changing in the content and ratio of cyclic nucleotides by apo TF stimulation of Ca-calmodulin-dependent phosphodiesterase.     

The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicks

We describe the effects of nitric oxide (NO) agonists and antagonists and the influence of a novel organoprotective pentadecapeptide BPC 157, on the development of pulmonary hypertension syndrome and tissue lesions in chicks. Acute toxicity, which includes single dose application of saline (1 mL intraperitoneally (ip)), BPC 157 (10 μg/kg bw), L-NAME (NO antagonist, doses 50, 100, 150 mg/kg bw) and L-arginine (NO agonist/100 mg/kg bw with their combination L-NAME + BPC 157; L-NAME + L-arginine) was investigated. In this experiment pathohistological examination of the spleen, heart, liver and lungs and hematological analysis was conducted. In the chronic toxicity experiment, the animals were treated daily for 5 weeks with L-NAME (10 mg/kg bw), L-arginine (100 mg/kg bw), BPC 157 (10 μg/kg bw) and their combinations (L-NAME + BPC 157; L-NAME + L-arginine) ip. Seven animals from each group, including controls (saline 1 mL ip) were killed every week. Application of L-NAME caused pulmonary hypertension syndrome (PHS) in the treated chicks, which was prevented by the simultaneous application of L-arginine and BPC 157. Pathohistological examination of both acute and chronic toxicity revealed that L-NAME caused severe tissue damage (myocardial and hepatic cell necrosis, necrosis of the lymphoid cells in the spleen) while L-arginine provoked predominantly congestion, edema and hemorrhages in all organs. The effect of L-NAME was successfully inhibited by the application of L-arginine and BPC 157 but the latter substance did not cause any tissue or organ damage. Hematological analysis shows significant hemoglobin and leukocyte number decrease in the L-NAME-treated groups of chicks.     

The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. III. Differential effect of two doses of adriamycin combined with 5 or 9 Gy of gamma-rays

The induction of reciprocal translocations in mouse germ cells by combined treatments with chemicals and ionizing radiations has been studied. Male mice were intraperitoneally injected with doses of 5 or 10 mg/kg of adriamycin (ADR) and irradiated with doses of 5 or 9 Gy of gamma-rays 24 h later. Three types of response were found after analyzing diakinesis-metaphase I multivalent configurations: potentiation, with the dose of 5 mg/kg of ADR plus 9 Gy; subadditivity, with the dose of 5 mg/kg of ADR plus 5 Gy; and additivity, with the dose of 10 mg/kg of ADR plus 5 or 9 Gy. According to these results, the subadditive effect observed with the lower dose of ADR plus 5 Gy cannot be explained under the assumption that depletion of any kind of spermatogonia is sufficient for modifying the chromosomal response of stem cells to ionizing radiations. The role of DNA repair mechanisms modulating the response of spermatogonial cells to combined treatments is discussed under the assumption that some repair mechanisms can be triggered by treatment with a low dose of a chemical and these repair mechanisms can reduce cell mortality. Consequently, a higher frequency of more radioresistant cells can survive.     

Antiradiation properties of adeturon and polyanion used separately and in combination

A study was made of the radioprotective effect of polyanion, a co-polymer of maleic and methacrylic acids, administered separately and in a combination with adeturon to irradiated (8 Gy, LD100/18) H male mice. Adeturon (300 mg/kg) was injected 15 min before, and polyanion (4 mg/kg) 24 h after gamma-irradiation. The effect of the preparations was assessed by the survival rate and hematologic indices (for instance, weight and cellularity of the spleen, bone marrow cellularity, and the number of leukocytes) at defined intervals within 30 days. Adeturon exerted a pronounced protective effect on the haemopoietic system of lethally exposed mice. The therapeutic effect of polyanion applied in a combination with adeturon was not enhanced and did not modify the effect of the latter.