Intra-peritoneal application of catechins and EGCG as in vivo inhibitors of ozone-induced oxidative stress.

Oxidative stress is considered as a prominent feature of many acute and chronic diseases as well as of the normal aging process. We examined the effects of intra-peritoneal administration of catechins and EGCG as in vivo inhibitors of oxidative stress induced by ozone administration in two groups of Wistar rats. The first group was treated by intra-peritoneal administration of catechins and EGCG after the administration of ozone and the second group was pretreated by intra-peritoneal administration of catechins and EGCG prior to ozone administration. We determined in blood the activity of the enzymes superoxide dismutase and glutathione peroxidase, total antioxidant capacity, levels of copper and zinc and in urine malonaldehyde contents. Ozone administration resulted in significant reduction of glutathione peroxidase activity, plasma zinc levels and plasma and Red Blood Cells antioxidant capacity. Catechins and EGCG upregulate superoxide dismutase activity and maintain plasma and Red Blood Cells antioxidant capacity. Malonaldehyde levels at the end of the study were significantly increased only in the first group. Our data demonstrate that treatment with catechins and EGCG cannot reverse or prevent the effects of oxidative stress although some modulation occurs.

Inhibition of benzo(a)pyrene-induced carcinogenesis by vitamin C alone and by vitamin C/vitamin E and selenium/glutathione.

The reduction on peroxidation caused by benzopyrenes by some naturally occurring antineoplastic agents was studied in this experimental work. Inhibition/reduction of experimental carcinogenesis induced by benzo(a)pyrene by vitamin C alone and by vitamin C/vitamin E and selenium/ glutathione was attempted in 224 female Wistar rats divided in four groups. Injected with 10.08 mL benzo(a)pyrene, the animals were treated with some naturally occurring substances like vitamin C alone and a combination of anticarcinogens. By calculating the carcinogenic potency of benzo(a)pyrene and the anticarcinogenic potency of substances used as well as histological examination of developed tumors and survival time of treated animals, it was found that vitamin C exerts a significant anticarcinogenic effect of 8.3 units and that the combination of the two anticarcinogens used produced a significant prolongation of the animals survival time with anticarcinogenic potency of 22.1 and 22.2 units, respectively. This is considered a potent anticarcinogenic effect. The question of an additional supportive administration of such agents complementary to the conventional cancer chemotherapy in humans is raised. Of course, further studies are needed.

Antiproliferative and anticarcinogenic effects of an aqueous preparation of Abies alba and Viscum album se abies, on a L-1210 malignant cell line and tumor-bearing Wistar rats.

Extracts of plants have been widely tested for possible anticarcinogenic properties. In the present study a traditional remedy, consisting of an aqueous extract of mixed parts of the tree Abies alba and its mistletoe Viscum album se abies was tested on benzo(alpha)pyrene(BaP)-induced tumors in Wistar rats and on the L-1210 malignant cell line. Two main groups of male Wistar rats subcutaneously injected by 10 mg of BaP, a dose inducing 100% carcinogenesis, a control group (C-G, 15 rats) and a treatment group(TR-G, 18 rats), were used for the study. Five animals bearing BaP-induced tumors were also tested (TR-1-G). Animals of the TR-G were orally administered with the aqueous extract at doses of 50 ml/kg b.w, from the day of BaP injection and of the TR-1-G, from the 120th day of injection, till death. L-1210 malignant cells in cultivation, were administered with a powder obtained by condensation and lyophilization of the extract, at various concentrations and cytotoxicity was measured by the microculture tetrazolium assay. Autopsy of the rats, revealed metastasis in the lungs of the animals of all groups and the tumors developed were histologically identified as leiomyosarcomas. The results indicated that the extract of the above plants possess anticarcinogenic effects, documented by: a) its antiproliferative effects on L-1210 cells (IC50 = 49.6 +/- 1.4 micrograms/ml), b) the significant prolongation of life and reduction of tumor growth rate of the animals of the TR-G in comparison to the C-G, c) the inhibition by 16.6% of tumor induction in the TR-G and d) the prolongation of life and the necrotic effects of the extract on the tumors of the animals in the TR-1-G. The antiproliferative effects of the Abies alba and Viscum album se abies extract may be due to the lectins and thionins contained in Viscum album, as well as to the monoterpenes contained in Abies alba. Soft tissue tumors sensitive to the extract, are widespread among human organs, even in larynx, and are usually resistant to chemotherapy.

Dose-related preventive and therapeutic effects of antioxidants-anticarcinogens on experimentally induced malignant tumors in Wistar rats.

A combination of antioxidants-anticarcinogens, consisting of vitamins C and E, selenium and 2-mercaptopropionyl glycine (2-MPG), was administered orally for the prevention (PRG) and treatment (TRG) of benzo(a)pyrene (BaP)-induced malignant tumors (leiomyosarcomas), in Wistar rats. In order to evaluate dose-related effects, a low dose vitamin (0.15 g/kg b.w. per day of vit.C and 0.05 g/kg b.w. per day of vit.E) and a high dose (1.5 g/kg b.w. per day of vit.C and 0.5 g/kg b.w. per day of vit.E) combination was administered, in prevention and treatment groups. Selenium was administered in doses of 2 microg/kg b.w. per day and 2-MPG in 15 mg/kg b.w. per day, in all groups. Daily estimations of 24 h urine volume levels of thiobarbituric acid reacting substances (MDA) were performed in 20 animals, divided into a control group, a BaP-injected group, a tricapryline-injected group and a BaP-injected and treated by the low dose combination group. Results revealed that the low dose combination failed to exert any beneficial effect on mean survival time of animals treated either preventitively or therapeutically. An increased number of animals bearing a second (lung) tumor was, in addition, found in autopsy and histological examination in the low dose combination (PRG and TRG) and the high dose TRG groups. The high dose combination groups manifested a significant prolongation of the mean survival time of animals; complete remission of tumors developed in 16.8% of the animals in the treatment group and a 5.2% prevention of tumor formation in the preventive group, without any evidence of an increased number of double tumor formation in the PRG group. Urine MDA increased significantly in animals injected by BaP during the first 10 days and since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prevention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that high doses (megadoses) of the antioxidant-anticarcinogen vitamins C and E in combination with carefully selected other antioxidants possessing supplementary actions, are probably needed in order to achieve a sufficient prevention and treatment of malignant diseases.

Enhancement of the antineoplastic effect of anticarcinogens on benzo[a]pyrene-treated Wistar rats, in relation to their number and biological activity.

Naturally occurring anticarcinogens, such as vitamins C and E, and the microelement selenium were found to inhibit the induction of benzo[a]pyrene-induced malignant tumors in Wistar rats to various extends. The antineoplastic effect of the tested anticarcinogens is gradually increased according to the number of inhibitors selected. To date the maximum action against malignancy is manifested by use of the above three inhibitors. In the group of rats receiving vitamins C, E and selenium, the prolongation of life induced by adding more than one anticarcinogen to the treatment regime reached, and in some cases surpassed, the normal life expectancy of the rats. It is expected that by adding even more anticarcinogens, the antineoplastic potency (Ap) of the inhibitors will be further improved. These results encouraged us to conduct a clinical trial in terminal human cancer cases, in conjunction with the usual treatments of surgery or chemotherapy and irradiation.