Ameliorative Effect of Green Tea Catechin Against Cadmium Chloride-Induced Testicular Toxicity in Mice.

The present study was designed to evaluate the effect of green tea catechin (7500 µg/kg/animal/day) against cadmium-induced testicular dysfunctions and oxidative stress in the testes of mice. For this purpose, Swiss albino mice were divided into six groups: group I, negative control; group II, catechin-treated control; group III, cadmium chloride (CdCl2)-treated control; group IV, experimental group I; group V, experimental group II; and group VI, experimental group III. Animals from all of these groups were necropsied at various post-treatment intervals between 12 hours and 30 days for various biochemical alterations in the testes. CdCl2 intoxication resulted in a significant decline in testicular total proteins, cholesterol, and alkaline phosphatase, whereas acid phosphatase and lipid peroxidation exhibited a noticeable augmentation as compared to negative control. Catechin treatment effectively protected CdCl2-induced alterations in all such parameters throughout the experiment. Catechin was effective in reducing the CdCl2-induced augmentation of phase I (P450 and CYPB5) as well as phase II (DT-diaphorase and glutathione-S-transferase) enzymes in testes. Furthermore, CdCl2 intoxication was found to attenuate the antioxidant potential of testes, which was however augmented when supplemented with green tea extract. Compared to CdCl2-treated control mice, superoxide dismutase, glutathione peroxidase, glutathione, and catalase levels were significantly decreased in testes. Indeed, green tea catechin significantly increased testicular antioxidant enzymatic activities compared to those given CdCl2 alone. In conclusion, the use of green tea extract appeared to be beneficial to a great extent in inhibiting and restoring the testicular injuries induced by CdCl2 intoxication in mammals.

Amelioration of chemical-induced skin carcinogenesis by Aegle marmelos, an Indian medicinal plant, fruit extract.

Chemoprevention is a novel approach to study the anti-initiating and anti-tumor-promoting efficacy of medicinal plants and their active principles. The present study investigated the chemopreventive potential of Aegle marmelos fruit extract in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis and its influence on oxidative stress and the antioxidant defense system. The oral administration of A marmelos at 100 mg/kg body weight/day during peri-initiational, postinitiational, and peri- & postinitiational phases of papillomagenesis showed significant reduction in tumor incidence, tumor yield, tumor burden, and cumulative number of papillomas when compared with carcinogen-treated control. The average latent period significantly increased (7.88 weeks; control group) to 9.45, 11.11, and 11.54 weeks in different A marmelos extract (AME) experimental groups. Enzyme analysis of skin and liver showed a significant elevation in antioxidant parameters such as superoxide dismutase, catalase, glutathione, and vitamin C in AME-treated groups when compared with the carcinogen-treated control. The elevated level of lipid peroxidation in the positive control was significantly inhibited by AME administration. These results indicate that AME has the potential to reduce chemical-induced skin papillomas by enhancing the antioxidant defense system.

Chemically induced skin carcinogenesis in mice and its prevention by Aegle marmelos (an Indian medicinal plant) fruit extract.

This study assessed the chemopreventive potential of the Aegle marmelos plant on mouse skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by croton oil. A significant reduction in tumor incidence, tumor burden, tumor multiplicity, and the cumulative number of papillomas, along with a significant increase in the average latent period, was recorded in mice treated orally with A. marmelos extract (AME) at peri - and post-initiation phases (i.e., 7 days before DMBA application and continued until the end of the experiment) of papillomagenesis as compared with the carcinogen-treated controls. Furthermore, a significant increase in catalase activity, reduced glutathione and total proteins, and a depleted level of lipid peroxidation were observed in liver and skin of AME-treated animals as compared with the carcinogen-treated controls. Thus, the oral administration of AME, at a dose of 50 mg/kg body wt per day per animal, was found to be significantly effective in reducing skin tumors against chemical carcinogenesis in mice.

Modulatory influence of Phyllanthus niruri on oxidative stress, antioxidant defense and chemically induced skin tumors.

The present study evaluates the modulatory potential of Phyllanthus niruri on chemically induced skin carcinogenesis, and its influence on oxidative stress and the antioxidant defense system. Oral administration of P. niruri extract (PNE), during peri- (Gr. III), post- (Gr. IV), or peri- and post- (Gr. V) initiational stages of 7,12-dimethylbenz(a) anthracene (DMBA)-croton oil­induced papillomagenesis considerably reduced tumor burden to 4.20, 4.00, and 3.33(positive control value 6.20); cumulative number of papillomas to 21, 16, and 10, respectively, (positive control value 62); and incidence of mice bearing papillomas to 50, 40, and 30%, respectively (positive control value 100%), but significantly increased the average latent period to 10.14, 10.62, and 11.60, and inhibition of tumor multiplicity to 66, 74,and 83%, respectively. Enzyme analysis of skin and liver showed a significant (p ≤ 0.05, ≤ 0.01, ≤ 0.001) elevation in antioxidant parameters such as superoxide dismutase, catalase, glutathione, and vitamin C in PNE-treated groups (Gr. III­V) when compared with the carcinogen-treated control (Gr. II). The elevated level of lipid peroxidation in the carcinogen-treated positive control group was significantly (p ≤ 0.05, ≤ 0.01, ≤ 0.001) inhibited by PNE administration. These results indicate that P. niruri extract has potentiality to reduce skin papillomas by enhancing antioxidant defense system.

Management of Radiation Injuries by Panax ginseng Extract.

Chemical radiation protection is an important strategy to protect living beings against the deleterious effects of radiation. In the present study, the radioprotective effect of hydro-alcoholic extract of Panax ginseng extract (PGR-HAE) was studied on radiation-induced deleterious alterations in Swiss albino mice. Oral administration of such extract (25 mg/kg b wt/day/animal) for 5 consecutive days, half an h. before whole-body exposure to 6 Gy gamma radiation, enhanced the 30 days survival and also inhibited the radiogenic sickness, weight loss and life shortening. PGR-HAE ameliorated radiation induced depletion in blood constituents at different necropsy intervals between 12 h to 30 d, and significantly increased the number of femoral spleen colony forming units that survived after irradiation. Furthermore, it checked depletion of glutathione and antioxidant enzymes (superoxide dismutase, catalase, and glutathione S-transferase) as well as elevation of lipid peroxidation (LPO) level in blood and liver. The significant reduction in the yield of LPO demonstrates that PGR-HAE protects the membranes against radiation-induced oxidative damage. These findings conclude that such plant extract provides significant radioprotection, and it may be potentially valuable in the prevention of injuries caused during planned and unplanned radiation exposure.

Protective effect of Alstonia scholaris against radiation-induced clastogenic and biochemical alterations in mice.

We studied the radioprotective effect of Alstonia scholaris bark extract (ASE) on cytogenetic alterations in the form of chromosomal aberrations and micronuclei induction in bone marrow. For this purpose, one group of male Swiss albino mice was exposed to 2.5 Gy gamma radiation to serve as the irradiated control, while the other group received ASE (100 mg/kg bwt/d) orally for 5 consecutive days 30 min before irradiation to serve as the experimental group. Results indicated that dicentrics and chromosomal exchanges were increased at 12 h post-exposure in both groups, followed by a gradual decline and then disappearance by d 15 and 7, respectively. However, the occurrence of chromatid breaks and acentric fragments was also maximum at 12 h, and later decreased without attaining the normal value, even up to the last necropsy interval. The percentage of such aberrations was significantly less in the ASE-pretreated irradiated animals. The incidence of chromosome breaks and centric rings kept increasing up to d 1, but then declined gradually and reached zero beginning at d 7; they were significantly lower in the ASE-treated irradiated group at the early intervals. A significant decrease in glutathione (GSH) and an increase in lipid peroxidation were observed after radiation exposure in untreated controls, whereas ASE-pretreated irradiated animals exhibited a significant increase in GSH and a decrease in lipid peroxidation; however, the values remained below normal. The results from the present study suggest that ASE pretreatment provides protection against radiation-induced chromosomal damage and micronuclei induction in the bone marrow of mice.

Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.

Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several isozymes of superoxide dismutase; the minerals selenium and zinc; and polysaccharides in aloe vera.

Influence of Rosemarinus officinalis extract on radiation-induced intestinal injury in mice.

The radioprotective effect of Rosemarinus officinalis extract (ROE) was studied in mice exposed to 3 Gy gamma radiation. Crypt survival, villus length, apoptotic cells, mitotic figures and goblet cells in intestine were studied at different autopsy intervals i.e. 12 hrs to 30 days after irradiation. Maximum changes in all the intestinal parameters were observed on day 3 after irradiation. Irradiated animals with ROE pretreatment exhibited a significant increase in the number of crypt cells, mitotic figures and villus length; whereas a significant decrease in the counts of apoptotic and goblet cells showed a significant decrease respective controls at all the autopsy intervals. Irradiation of animals resulted an elevation in lipid peroxidation and a reduction in glutathione concentration in the intestine at 1 hour post-irradiation. In contrast, ROE treatment before irradiation caused a significant depletion in lipid peroxidation and elevation in glutathione levels.

Anticancer activity of an Indian medicinal plant, Alstonia scholaris, on skin carcinogenesis in mice.

Alstonia scholaris, commonly known as sapthaparna, has been used for centuries in Ayurvedic medicine for treatment of various disorders. The objective of this study was to investigate the possible chemopreventive and anti-oxidative properties of this medicinal plant on two-stage process of skin carcinogenesis induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 lg/100 ll acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks) in Swiss albino mice.The tumor incidence, tumor yield, tumor burden and cumulative number of papillomas were found to be higher in the carcinogen treated control (without ASE treatment) as compared to experimental animals (ASE treated). Furthermore, a significant increase in reduced glutathione, superoxide dismutase and catalase but decrease in lipid peroxidation was measured in ASE administered experimental groups than the carcinogen treated control. The present study demonstrates the chemopreventive potential of Alstonia scholaris bark extract in DMBA-induced skin tumorigenesis in Swiss albino mice.

Radioprotective effects of Aloe vera leaf extract on Swiss albino mice against whole-body gamma irradiation.

The skin, being a cell-renewal system, is one of the first organs to be affected in total-body irradiation during radiotherapy. An attempt has been made in the present study to explore radiation-induced biochemical alterations caused by whole-body gamma irradiation and their modulation in Swiss albino mice by Aloe vera leaf extract (AVE). Mice were selected for this study from an inbreed colony and divided into four different groups: I (double-distilled water-treated group): considered as normal; II (Aloe vera-treated group): the animals were administered 1 g/kg body-wt/day Aloe vera leaf extract; III (radiation-treated group): the animals were exposed to 6 Gy gamma radiation at the dose rate of 0.96 Gy/min; and IV (combination group): animals were administered Aloe vera leaf extract continuously for 15 consecutive days, and on the 15th day they were irradiated to 6 Gy gamma radiation after 30 minutes of extract administration. The animals from the above groups were autopsied after 6 hours, 24 hours, and at 3, 7, 14, and 21 days of radiation. Biochemical estimations of DNA, lipid peroxidation, glutathione, catalase, and superoxide-dismutase were made. Total DNA, catalase, superoxide dismutase (SOD) activity in the skin, and glutathione (GSH) in the liver and blood significantly decreased compared to normal, but lipid peroxidation (LPO) in the liver and blood increased in the irradiated control group. In contrast, in experimental animals, DNA, catalase, and SOD in the skin and GSH in the liver and blood increased significantly, whereas LPO in the liver and blood decreased in comparison to irradiated control animals. Thus, Aloe vera leaf extract is found to have damage-resistant properties against radiation-induced biochemical alterations in Swiss albino mice.

Amelioration of radiation-induced hematological and biochemical alterations by Alstonia scholaris (a medicinal plant) extract.

The radioprotective efficacy of a hydro-alcoholic extracted material from the bark of Alstonia scholaris (ASE) was studied in mice against radiation-induced hematological and biochemical alterations. Swiss albino mice were administered ASE (100 mg/kg body weight/d for 5 consecutive day) orally prior to whole-body gamma irradiation (7.5 Gy). Radiation exposure resulted in a significant decline (P<.001) in erythrocytes and hemoglobin until the third day, following a gradual recovery (ie, day 7), but these values did not reach normal values during the remainder of the animals' life span. Hematocrit percentage declined significantly (P<.001) until day 15. In contrast, ASE-pretreated irradiated animals had significantly higher erythrocyte, hematocrit, and hemoglobin values than the irradiated controls. Furthermore, a significant elevation in lipid peroxidation level over normal was recorded in gamma-irradiated mice, whereas this increase was considerably lower in ASE-pretreated animals. Pretreatment with ASE caused a significant increase in glutathione levels in serum as well as in liver in comparison to irradiated animals. This study showed that ASE protects against radiation-induced hematological and biochemical alterations in Swiss albino mice.

Chemopreventive potential of Aloe vera against 7,12-dimethylbenz(a)anthracene induced skin papillomagenesis in mice.

The present investigation was undertaken to explore the antitumor-promoting activity of Aloe vera on 2-stage skin carcinogenesis, induced by a single topical application of 7,12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 16 weeks in Swiss albino mice. Oral administration of aloe leaf extract at a dose of 1000 mg/kg body weight/d and aloe gel treatment at a dose of 1 mL/9 cm(2)/mice/d was found to be effective in decreasing the number and size of the papillomas. A significant reduction in tumor incidence (40.00+/-5.10, 30.00+/-3.25, and 40.00+/-4.12 for aloe gel, aloe gel and aloe leaf extract combined, and aloe leaf extract alone, respectively) was observed in animals in the aloe extract- and aloe gel-treated groups compared with 100% tumor incidence in the control group. The cumulative number of papillomas during an observation period of 16 weeks was significantly reduced in the aloe-treated groups (8.0+/-0.34, 6.00+/-1.10, and 9.00+/-1.41 for aloe gel, aloe gel and leaf extract, and aloe leaf extract, respectively) compared with a 36+/-0.98 cumulative number of papillomas in the control group. The average latent period was significantly increased from 4.9+/-0.10 weeks in the control group to 6.37+/-0.12, 6.8+/-0.25, and 6.2+/-0.21 weeks in the aloe-treated groups, respectively. The tumor burden and tumor yield were significantly decreased (2.0+/-0.25, 2.00+/-0.30, and 2.25+/-0.2 and 0.8+/-0.25, 0.6+/-0.32, and 0.9+/-0.28, respectively) as compared with the 7,12-dimethylbenz(a)anthracene-treated control group (3.6+/-0.10 and 3.6+/-0.19). Furthermore, treatment with aloe gel and/or extract by topical and/or oral administration resulted in a significant increase in the reduced glutathione (P< .05), DNA (P< .001), catalase (P< .05), and protein (P< .001) in the skin of mice. Conversely, lipid peroxidation levels were significantly decreased (P< .001) in the skin of mice.

Protective effect of diltiazem (a calcium channel blocker) against cadmium-induced toxicity in mice.

Protective efficacy of diltiazem (a calcium channel blocker) has been studied against cadmium chloride (CdCl2) induced hematological and biochemical alterations in Swiss albino mice. CdCl2 (5 mg/kg b.wt.; i.p.) with or without prior treatment of diltiazem (100 mg/kg b. wt.; i.p.) was given to six-week old mice. Significant increase in the number of bone marrow cells as well as hematological parameters was observed in diltiazem pretreated CdCl2 intoxicated animals. A significant increase in lipid peroxidation (LPO) and acid phosphatase (ACP) level, and decrease in glutathione (GSH) and alkaline phosphatase (ALP) level in blood as well as liver were measured in CdCl2 intoxicated mice, while such values were near normal in DTZ pretreated animals. Furthermore, a significant increase in erythropoeitin (EPO) level was observed in diltiazem (DTZ) pretreated CdCl2 intoxicated animals as compared to CdCl2 alone treated animals. Thus, Diltiazem administration before cadmium intoxication protects bone marrow and hematological constituents in mice.

Radioprotective potential of Rosemarinus officinalis against lethal effects of gamma radiation : a preliminary study.

The radioprotective effect of Rosemarinus officinalis extract (ROE) was studied in mice exposed to 8 Gy of gamma radiation. The optimum dose for radioprotection was determined by administering 100, 200, 400, 800, 1000, 1500, and 2000 mg/kg body weight of ROE orally once daily, consecutively for five days before irradiation. Treatment of mice with ROE, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug-treated irradiated controls. The dose of ROE found to be most effective against radiation was 1000 mg/kg body weight because this dose increased the survival time and reduced the mortality rate of mice significantly. Body weight loss in ROE administered irradiated animals was significantly less in comparison with animals who were given radiation treatment alone. Furthermore, irradiation of animals resulted in an elevation in lipid peroxidation (LPx) and a significant decrease in glutathione (GSH) in blood and liver. Conversely, administration of animals with ROE before irradiation caused a significant decline in LPx accompanied by a significant increase in GSH concentration. The present study demonstrates that Rosemarinus officinalis leave extract is a good radioprotector.

Emblica officinalis (Linn.) fruit extract provides protection against radiation-induced hematological and biochemical alterations in mice.

Oral administration of Emblica officinalis (Linn.) before exposure to gamma radiation was found to be effective in protecting mice against the hematological and biochemical modulation in peripheral blood. A significant increase in the RBC, WBC, hemoglobin, and hematocrit values was observed in the animals pretreated with E. officinalis extract as compared to the hematological values observed in the irradiated group. Furthermore, radiation sickness was greatly inhibited in those mice that were irradiated with prior treatment of E. officinalis. A significant decrease in glutathione (GSH) content and increase in lipid peroxidation (LPx) level were also observed in irradiated animals; whereas E. officinalis pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPx level, but such remained below the normal. The results from the present study suggest that E. officinalis pretreatment provides protection against irradiation to Swiss albino mice.