Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

Effects of Hesperidin as a Radio-protector on Apoptosis in Rat Peripheral Blood Lymphocytes after Gamma Radiation.

INTRODUCTION: Hesperidin (HES), as the most abundant flavonoid existing in the citrus, is widely used by human daily. The radio-protective effects of Hesperidin have been confirmed in various measurement systems. This study aimed to evaluate the effects of Hesperidin on the changes in the apoptosis level and expression of apoptotic genes target (bax, bcl-2 and ration of bax/bcl-2) in the peripheral blood lymphocytes of male rats after gamma radiation. MATERIALS AND METHODS: 64 male rats were divided into eight groups: Control, HES (100 mg/kg b.w, orally, 7 days), whole body irradiation with 2 and 8Gy, pre-administrated with 50 and 100 mg/kg body weight of Hesperidin for 7 days before irradiation with 2 and 8 Gy. 24 hours after radiation, apoptotic lymphocytes were evaluated using PE Annexin V Apoptosis detection I kit and the levels of mRNA for bax and bcl-2 were evaluated by real time reverse transcription polymerase chain reaction. RESULTS: A significant reduction in apoptosis of the lymphocytes was demonstrated in group animals receiving 8 Gy compared to the group which received 2 Gy irradiation (p<0.0001). However, apoptosis significantly increased in group of rats who received Hesp before irradiation (p<0.05). The increase of apoptosis by Hesperidin administration can be attributed to the decreased expression of bax and significantly reduced expression of bcl-2 and finally increasing the ration of bax/bcl-2. CONCLUSION: The results suggest that administration of 50 and 100 mg/kg of Hesperidin induces apoptotic effects by changing expression level of bax, bcl-2 and also the ratio of bax/bcl2.

Radioprotective effect of chicory seeds against genotoxicity induced by ionizing radiation in human normal lymphocytes.

The search for less-toxic radioprotective agents has led to a growing trend towards natural products. Protective effect of the methanolic extract of chicory seeds (MCS) was investigated against genotoxicity induced by ionizing radiation in human lymphocytes. Human peripheral blood samples were collected and incubated with MCS at different concentrations (10, 50, 100, and 200 µg/mL) for two hours. The whole blood samples were exposed in vitro to X-ray at dose 2.5 Gy. Then, the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus in cytokinesis blocked binucleated cell. The methanolic extract at all doses significantly reduced the frequency of micronuclei in binucleated lymphocytes, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection was observed at 200 µg/mL of MCS, it completely protected genotoxicity induced by ionizing radiation in human lymphocytes. The extract exhibited a concentration-dependent radical scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. HPLC analysis of MCS showed this extract is containing chlorogenic acid as a phenolic compound. These data suggest that the radioprotective effect of methanolic extract of chicory seeds can be attributed to the presence of phenolic compounds such as chlorogenic acid which act as antioxidant agents.

In vitro protective effect of atorvastatin against ionizing radiation induced genotoxicity in human lymphocytes.

Atorvastatin (AT) is widely used as a medication for treatment of hypercholesterolemia. Recent studies showed that AT enhanced cell toxicity induced by ionizing radiation in cancerous cells. In this study, the radioprotective effect of AT was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with AT at different concentrations (0.05, 0.1, 1, or 10 µM) for two hours. The whole blood was exposed to X-ray at dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. AT exhibited a significant decreasing in the frequency of micronuclei in human lymphocytes exposed to ionizing radiation, as compared to with similarly irradiated lymphocytes without AT treatment. The maximum protection and higher decreasing in frequency of micronuclei was observed at 10 µM of AT (68% decrease), providing maximal protection against ionizing radiation. This data is promising for protection human normal cells from the genetic damage induced by ionizing irradiation.

Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice.

This study investigated the radioprotective effects of a naturally occurring dipeptide, carnosine, on testicular damage. Carnosine was administered (10, 50 and 100 mg kg(-1) body weight) to male mice via intraperitoneal injection for 4 days prior to gamma irradiation (2 Gy). Apoptosis with the TUNEL assay and histopathological parameters were evaluated 12-h and 14-day post-irradiation. Pre-treatment with carnosine before irradiation significantly reduced the frequency of TUNEL-positive cells induced by radiation treatment at all doses by reduction factors of 1.8, 2.47 and 2.23 for carnosine at 10, 50 and 100 mg kg(-1) bw, respectively, unlike that observed in the radiation alone group. Exposure to ionising radiation decreased sperm count and reduced the height and diameter of seminiferous epithelial tubules. Pre-treatment with all doses of carnosine significantly augmented seminiferous epithelial height and tubule diameter and also increased the number of germinal cells in comparison to the group treated with radiation only. These results indicate that carnosine prevents testicular dysfunction induced by gamma-irradiation via an anti-apoptotic effect; this restoration of proper testicular function ultimately leads to the recovery of spermatogenesis.

Diospyros lotus L. fruit extract protects G6PD-deficient erythrocytes from hemolytic injury in vitro and in vivo: prevention of favism disorder.

OBJECTIVE: The aim of this study was to evaluate the protective effect of Diospyros lotus L. fruit extract against the hemolytic damage induced by Vicia faba beans extract in both G6PD enzyme-deficient human and rat erythrocyte in vitro and in vivo. MATERIALS AND METHODS: In the former model, venous blood samples were obtained from five subjects with known G6PD deficiency and erythrocyte hemolysis induced by Vicia faba L. bean extract was asessed spectrophotometrically in the presence and absence of Diospyros lotus L. fruits extract. In the in vivo model, G6PD-deficient rats (induced by intraperitoneal injection of dehydroepiandrosterone for 35 days) pre-treated with different doses of Diospyros lotus L. (500, 750, 1000, and 1500 mg/kg, p.o for 7 days) were challenged with Vicia faba beans extract and the protective effect of the fruit extract against hemolysis was evaluated as above. RESULTS AND CONCLUSIONS: The results have shown that Diospyros lotus L. fruits extract has antioxidant activity that may protect against hemolytic damage induced by Vicia faba bean extract in both G6PD-deficient human and rat erythrocytes. The study gives a scientific basis for the efficacy of the fruit extract as used in Iran. The fact that this was shown in human erythrocytes in vitro is significant and provides a rationale for further testing in vivo in G6PD-deficient human populations.

The radiotracer (99m)Tc-MIBI is not genotoxic for human peripheral blood lymphocytes at diagnostic radioactive dose.

The radiotracer technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) has been widely used for myocardial blood flow imaging. We investigated the genotoxicity of (99m)Tc-MIBI in cultured human lymphocytes at the same concentration used in patients. Radioactivity doses were determined in whole blood at 5 min post-injection of 20 mCi (99m)Tc-MIBI in patients. Subsequently, whole blood of human volunteers was incubated with 1, 2.3, 4 or 8 microCi (99m)Tc-MIBI. After a 30-min incubation, the lymphocytes were stimulated with a mitogen to assay for micronuclei in cytokinesis-blocked binucleated cells. The frequency of micronuclei in samples treated with this radiopharmaceutical up to 2-fold (8 microCi) the concentration of (99m)Tc-MIBI normally found in the blood of patients was not more than in control lymphocyte cultures. We concluded that there is no increased induction of micronuclei in lymphocytes incubated with (99m)Tc-MIBI at the radioactivity doses used for diagnostic purposes.

The alteration of plasma's zinc and copper levels in patients with burn injuries and the relationship to the time after burn injuries.

INTRODUCTION: Burn injury is a medical problem as well as a social burden on the national health services in developing countries. Trace elements have important roles in wound healing and act as antioxidants. In this study, zinc (Zn) and copper (Cu) levels in plasma of burned patients and their relationship with the burn surface area and time-related pattern are determined in the admitted patients after burn injury. METHODS: 37 patients were divided into two groups: Group 1 consisted of 16 patients with burn injuries less than 20 percent of the total burn surface area, and Group 2 consisted of 21 patients with burn injuries between 20 and 40 percent of the total burn surface area. The control group consisted of 20 subjects. The Zn and Cu levels were determined one, three, seven and 14 days after the occurrence of burn injury. These trace elements were determined using atomic absorption spectrophotometer. RESULTS: These trace elements in plasma significantly decreased on all days after admission and the levels were lower than those of the control group. There was no significant relationship between Groups 1 and 2 in Cu and Zn concentrations on different days. We did not find any difference between burn surface area and Zn and Cu concentrations in these groups. CONCLUSION: Based on the critical role of plasma's Zn and Cu rate in wound healing and their relationship in decreasing the burn injury, it is important that patients having burn types II and III take Zn and Cu supplements continuously as micronutrients after burn injury.

Radioprotective effects of chlorogenic acid against mortality induced by gamma-irradiation in mice.

The radioprotective effects of the naturally occurring compound chlorogenic acid have been investigated against mortality induced by gamma-irradiation in mice. Chlorogenic acid was administrated at single doses of 100, 200 and 400 mg/kg 1 or 24 h prior to lethal dose of gamma-irradiation (8.5 Gy). At 30 days after treatment, the percentage of survival in each group was as follows: control, 20%; 100 mg/kg, 20% and 15%; 200 mg/kg, 45% and 15%; 400 mg/kg, 25% and 35% for 1 h and 24 h treatment prior gamma-irradiation, respectively. Survival rate was statistically increased in animals treated with this agent at 200 mg/kg at 1 h prior to irradiation as compared with the irradiation only group. Other doses of chlorogenic acid have not showed any enhanced survival when it was administrated at 1 or 24 h before irradiation. Chlorogenic acid exhibited concentration-dependent activity on 1,1-diphenyl-2-picrylhydrazyl free radical to show strong antioxidant activity. It appeared that chlorogenic acid with antioxidant activity reduced mortality induced by gamma-irradiation.

Radioprotective effects of hesperidin against gamma irradiation in mouse bone marrow cells.

The radioprotective effects of hesperidin (HES), a flavonone glucoside, were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal (ip) administration of hesperidin at doses of 10 mg kg(-1), 20 mg kg(-1), 40 mg kg(-1), 80 mg kg(-1) and 160 mg kg(-1) 45 min prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All five doses of HES significantly reduced the frequencies of MnPCEs and increased PCE/PCE+NCE ratio in mice bone marrow compared with non-drug-treated irradiated control (p<0.0001). There was a drug dose-response effect of HES in reducing MnPCE and increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum reduction in MnPCE was observed in mice treated with HES at a dose of 80 mg kg(-1). The total MnPCE values were 2.85 fold less in the 80 mg kg(-1) HES group after being exposed to 2 Gy of gamma-rays than those in the respective irradiated control. Our study demonstrates that hesperidin has powerful protective effects on the radiation-induced DNA damage and on the decline in cell proliferation in mouse bone marrow.

Chemoprotective effects of captopril against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

The protective effects of captopril (CAP) against toxicity induced by cyclophosphamide (CP) in mice were investigated using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells and liver glutathione (GSH) content. A single intraperitoneal (i.p.) injection of CAP at 50, 100, and 200 mg/kg 1 h prior to cyclophosphamide (50 mg/kg) reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs). All three doses of CAP significantly reduced the frequency of MnPCEs in mouse bone marrow compared to the group treated with CP alone (P<0.0001-0.01). CP significantly depleted the GSH content in liver but the application of CAP at a dose of 100 mg/kg 1 h before CP treatment repleted the GSH content. CAP exhibited concentration-dependent antioxidant activity, scavenging >96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. It appears that CAP, due to its antioxidant activity and by increasing GSH levels, can modulate the reduced cellular thiol content induced by CP and reduce the genotoxicity of CP in bone marrow cells.

Spectrophotometric determination of captopril with DTNB reagent in pharmaceutical formulation.

A simple and sensitive spectrophotometeric method has been developed for the determination of captopril in its dosage form. The method is based on the reaction of the drug with DTNB reagent in pH 8 to produce a yellow coloured species measurable at 412 nm. The absorbance-concentration plot is linear over the range 1-10 x 10(-5) M with correlation coefficient of 0.997. The molar absorptivity and minimum delectability were 13553 and 3.2 x 10(-7) respectively. The proposed method was applied successfully for determination of captopril in its tablets form. The mean quantity and recovery were found to be 25.01+/-2% and 100.04+/-2% (each tablet contain 25 mg captopril). Quantification of the same tablets was determined by a standard method such as HPLC. The mean quantity of each tablet was found to be 25.07+/-1.22% by using HPLC method. It was not statistically, significant difference between Ellman's and HPLC method. This proposed method can be successfully applied to the determination of captopril in water and its dosage form and can use instead HPLC.

Radioprotective effects of 2-iminothiazolidine derivatives against lethal doses of gamma radiation in mice.

Although thiol-containing compounds have long been known to possess radioprotective properties, their therapeutics utility is limited by their side effects at radioprotective doses. In this study, a series of 2-iminothiazolidine derivatives were prepared and their toxicity and radioprotective effects in NMRI mice were determined using the LD50/30 end point. The LD50 values, as determined by a Probit analysis, were between 11 and 14 mg/kg. For studying radioprotective effects, one-sixth of the toxic LD50 values were used, namely 2 and 2.2 mg/kg. To evaluate the radioprotective capabilities, mice were exposed to lethal doses of cobalt-60 gamma-radiation alone or in the presence of compounds. The percentage survival of mice at 30 days for these compounds compared to control mice were 10 to 30% when injected 15 and 30 minutes before gamma-irradiation. They were significant compared to the control group (P < 0.05). 2-Imino-3-(benzoylmethyl)thiazolidine derivatives showed different radioprotective effects when injected at different times before irradiation, but were not statistically significant from each other (P > 0.05).