Echitamine chloride was tested for its anti-cancer effect on fibrosarcoma cells and far toxicity toward vero cells, a representative “normal” cell. In vitro incubation of these cells with different concentrations of echitamine chloride demonstrated the non-toxic nature of this drug on vero cells and its anti-cancer effect on sarcoma cells. The latter included reductions in cell viability, glutathione content, and [3H]-thymidine incorporation and increased lipid peroxidation. Interestingly, echitamine chloride caused 55% cell death at a concentration of 200μM in the case of sarcoma cells whereas vero cells were not affected even at the maximum concentration tested, i.e., 200μM.
Maximum binding capacity and dissociation constant of the triiodothyronine receptor were studied in isolated hepatic nuclei of thyroglobulin-immunized rabbits on the 98th day after the first injection. Study revealed a significant (p<0.001) increase in maximum binding capacity and in dissociation constant and significantly lower (p<0.001) levels of serum triiodothyronine and thyroxine. These results reflect an alteration in thyroid hormone binding capacity during experimental thyroglobulin immunization.
The effects of a cytotoxic drug, cyclophosphamide, and an antioxidant, vitamin E, both individually and also in combination were studied in fibrosarcoma-induced rats. The rate of formation of lipid peroxides was analyzed in untreated, cyclophosphamide- (20mg/kg body weight) and α-tocopherol- (400 mg/kg body weight) administered animals along with that of their respective controls. The levels of non-enzymic antioxidants, like glutathione and vitamin E, and enzymic antioxidants, viz., catalase, superoxide dismutase, and glutathione peroxidase, were analyzed as well. Significantly increased level of lipid peroxides was observed with a concomitant decrease in enzymic and non-enzymic antioxidants in fibrosarcoma-bearing rats when these levels were compared with those of the respective controls. A further increase in lipid peroxides and a decrease in the level of antioxidants were observed in the cyclophosphamide-treated animals. In vitamin E-treated, fibrosarcoma-bearing rats, there was a decrease in lipid peroxide level, and an increase in antioxidant level, probably due to the free radical-quenching activity of vitamin E. When cyclophosphamide was administered in combination with vitamin E to the fibrosarcoma-bearing rats, the corrected levels of these parameters were observed to approach the control values. From these results, we infer that vitamin E is beneficial combinative factor for controlling the increased risk of lipid peroxidation induced by cyclophosphamide. Thus, vitamin E augments the anticarcinogenic activity of cyclophosphamide by decreasing its cytotoxic effect, which is enhanced by lipid peroxidation.
The biological impact of selenium on the levels of antioxidant enzymes in Wistar rats bearing mammary tumor induced by dimethylbenz(a)anthracene was investigated. Control rats and tumor-bearing rats were fed a normal diet or one containing 5mg sodium selenite/kg diet from the day of tumor induction. The reduced levels of ceruloplasmin, ascorbic acid, and α-tocopherol seen in the serum of tumor-bearing rats on the normal diet were found to be increased by the selenium treatment. The activities of superoxide dismutase and catalase in tumor-bearing rats were decreased significantly when compared with those of control rats, whereas selenium administration caused a considerable recovery of the activities of these enzymes in the rats with tumors. The increase in the levels of these enzymes was found to be predominantly significant in the liver. These observations clearly suggest an antioxidant role for selenium in experimental mammary tumor.
Flavin adenine dinucleotide (FAD) is one of the cofactors of nitric oxide synthase (NOS). Recently, we found that FAD acted as an allosteric activator of holo NOS of the neuronal type. In the present study, we obtained the following results in rats: 1) FAD enhanced cyclic GMP (cGMP) production in primary cultures of neuronal cells and its effect was completely abolished by preincubation of the cells with a potent inhibitor of NOS, NG-monomethyl-L-arginine. 2) FAD injection into the lateral cerebral ventricle decreased the blood pressure and heart rate. This effect was suppressed by preadministration of NG-monomethyl-L-arginine. 3) The reduction in the blood pressure and heart rate by FAD was accompanied by suppression of the neural activity of the sympathetic efferents to the kidney. This effect was blocked by preadministration of NG-monomethyl-L-arginine. 4) Intravenous injection of FAD also caused reductions in the blood pressure and heart rate. These results suggest that FAD activates NOS in neuronal cells and that the resultant NO reduces the blood pressure by suppressing sympathetic nerve activity. We also obtained evidence that FAD regulates the cardiovascular system when administered peripherally.
The influence of arginine on healing skin wounds was studied in rats. Full-thickness excision wounds were made on the back of rats and 150mg arginine was administered orally, intraperitoneally, or topically. The granulation tissue formed was used for the estimation of collagen, hexosamine, protein, and DNA. There was a significant increase in collagen, hexosamine, and protein content, whereas no increase in DNA content occurred. This may suggest a non-mitogenic activity of arginine. The tensile strength of treated wounds also increased significantly, and the increase was 72% in intraperitoneally treated rats. The period of epithelialization was decreased, and rate of contraction increased significantly in the treated groups.
Effects of vitamin A deficiency on vitamin E were evaluated in two different situations in which the vitamin A intake was notably reduced. On the one hand, dogs on an equilibrated diet were submitted to intestinal resection; hence vitamin A was poorly absorbed, compared with a control group. On the other hand, deficit of vitamin A was provoked in rats feeding them with a vitamin A-deficient diet. In both cases vitamin A plasma levels were decreased on comparing them with the corresponding control groups. In these two cases symptoms of vitamin A deficiency were observed as loss of muscular mass and nephrolithiasis. It is interesting to point out that when vitamin A was depleted by either of the methods, the vitamin E plasma level noticeably increased.