A greater understanding of the etiology of rheumatoid and other inflammatory diseases, their association with reactive oxygen species (ROS), and the role of environmental chemicals as antigens, has opened the way to new approaches in disease prevention and treatment by dietary modulation. Normal protection against the inflammatory effects of ROS (antioxidant defense) and environmental chemicals (detoxication) requires constant dietary replenishment to provide the redox buffer, glutathione (GSH), the antioxidant vitamins, E, C, and A, and other essential components such as selenium for the GSH peroxidase enzymes. Fasting and some environmental chemicals (haloalkanes) induce the ROS-generating enzyme cytochrome P4502E, as also does inorganic iron; and the various dietary lipids provide prostanoids of different inflammatory potentials. Adequate calories (NADPH) are essential for maintaining the two defense systems, but caloric excess may lead to changes in membrane composition, electron leakage, ROS generation, and exacerbation of the inflammatory condition.
6B3 antigen, a serum component released by various human malignant cells, was examined for its effect on cultured cells, and a possibility was raised that it suppresses B cell function. The 6B3 antigen, purified from culture supernatants of a human lung cancer cell line, HLC-2, can bind to the surface of surface immunoglobulin (sIg)-positive cells in general and exerts cytostatic and cytocidal effects on them. On the other hand, it did not bind to sIg-negative cells. The binding was inhibited by soluble immunoglobulins only at high concentrations, suggesting that the antigen, which has a decameric subunit structure, has strong affinity for clustered sIg, whereas its affinity for monomeric immunoglobulins is relatively low.
Effect of endurance exercise training on hepatotoxicity induced by aflatoxin B1 (AFB1) was studied in rats. Rats were subjected to swimming with 1%BW resistance for 30min, 5 days/week for 14 weeks before administration of AFB1. Endurance exercise training induced high physical fitness as shown by reduction in resting heart rate and increase in the activities of mitochondrial succinate dehydrogenase and citrate synthase in the gastrocnemius muscle. Water-immersed rats had similar basal physical fitness when compared with that of the untrained rats. Endurance exercise training as per the above schedule followed by a single i.p. injection of AFB1 (2mg/kg BW) caused a significant increase in the activities of serum alanine aminotransferase (ALT) by 6.6 fold and aspartate aminotransferase (AST) by 1.8 fold and increased the severity of histopathologic hepatic necrosis at 24h after AFB1 administration. Endurance exercise training potentiated AFB1-induced hepatotoxicity by increasing the activity of the hepatic monooxygenase enzymes aniline hydroxylase and p-nitroanisole-O-demethylase. These results suggest that potentiation of AFB1-hepatotoxicity by endurance exercise training may be due to an increase in the metabolic formation of AFB1-8, 9-oxide, which, in turn, causes a marked increase in AFB1 binding to hepatic DNA and proteins.
Alterations in the levels of copper, zinc, and cadmium were investigated in both serum and buccal mucosa of hamsters in progressive pathology, namely, hyperplasia, papilloma, early invasive carcinoma, and well-differentiated squamous cell carcinoma. Hamster buccal pouch carcinogenesis was induced by tri-weekly topical application of a 0.5% solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in liquid paraffin applied with a brush on the right buccal mucosa for 16 weeks. Serum copper levels and the copper/zinc ratio were generally elevated, and serum zinc levels were generally depressed, during carcinogenesis; and these alterations were related to the advancing stages of carcinogenesis. In transformed buccal mucosa, a significant decrease in the level of copper and a significant increase in the level of zinc were seen with papillomatous tissues onwards, and the alterations were progressive with the development of carcinomas. The changes in the levels of cadmium were moderate and occurred only in carcinomas. These data suggest that the alterations in the levels of copper, zinc, and copper/zinc ratio may be used as markers for pathological changes in the malignant transformation of oral mucosa.
Chronic oral intake of morphine sulphate leads to tolerance toward intestinal action and reduced nutritional uptake. The mechanism involved in this tolerance was clarified by studying the levels of intestinal cellular macromolecules and activities of intestinal membrane-bound key enzymes connected with the transport of nutrients. In vivo intestinal absorption of [14C]glucose and [14C]glycine was examined to study the precise relationship between involvement of enzymes and transport of these labelled nutrients. Male Wistar rats were made morphine dependent. The levels of carbohydrates and glycogen and activities of adenosine triphosphatase, Na+K+-dependent ATPase, and alkaline phosphatase were decreased in the morphine-treated rats. This altered enzyme activity concurred well with the absorption of labelled nutrients and was reflected in the cellular macromolecular levels of carbohydrates and glycogen. Results from this study indicate that animals develop tolerance through DNA, RNA, and protein synthesis and altered nutritional uptake through defective enzyme machinery, thus explaining the adverse effect of morphine sulphate.
We studied the effects of Maccha and alcohol extracts of Maccha and Mate tea in streptozotocin (STZ)-induced diabetic rats. By the continuous feeding of these substances prior to STZ administration, the elevations of urinary glucose excretion and fasting blood sugar were suppressed, suggesting alleviation of diabetic manifestations. At the same time, the increase in serum lipids, which is a sign of complications in diabetes, was also suppressed; and the concentrations of serum and liver thiobarbituric acid-reactive substance (TBARS) were significantly decreased. The decrease in liver NAD was also suppressed, indicating alleviation of disorders caused by oxidation in the body. The serum uric acid level, which is assumed to elevate in diabetes to compensate for the disorders attributable to oxidation, was significantly lowered. These results suggest that antioxidant components such as the catechins contained in the tested tea leaves act to scavenge STZ-induced radicals and thereby alleviate the disorders caused by oxidation in the body attributable to the formation of radicals.
Breast cancer incidence is three to four fold higher in the Parsi ethnic community than in the Non-Parsi population living in the same area. Parsis are westernized in their life style and some studies have reported that their dietary habits are comparable to those of Europeans. The question as to why the Parsis show such a high incidence of breast cancer remains, however, without a satisfactory answer. Besides genetic factors, claimed differences in the dietary intake of the Parsis could perhaps provide a lead to find an answer to this question. The present study addressed the role of diet, its composition, and the caloric intake in the Parsis in relation to the high incidence of breast cancer reported among them. We analyzed the composition of serum lipids and fatty acids in relation to the food consumption among Indian (Parsis and Non-Parsis) and French patients with breast cancer. The data obtained were compared with those from women with benign lesions and from normal subjects. Our findings revealed that the food habit and the quality of food intake were grossly the same among the Parsis, the Non-Parsis, and the Europeans. The caloric intake, however, was higher in Parsi women with a breast cancer history as compared with that in Non-Parsi or European patients. In general, the overall caloric intake among breast cancer patients was higher than that of those with benign breast lesions or the control individuals. On the other hand, we observed no significant difference in the levels of total cholesterol, triglycerides, and phospholipids between the European and the Indian patients or the controls. We also focused attention on the saturated and unsaturated (mono and poly) fatty acids. A proportional variation of the monounsaturated fatty acids in free fatty acids and of the polyunsaturated ones in phospholipids was seen in different categories of the individuals. Current views on promotion and initiation of cancers imply a major role for environmental factors, particularly the diet. Our results do not indicate that the dietary intake of Parsis is the major risk factor involved in the etiology of breast cancer. In any case, it alone can not account for the high incidence of breast cancer seen in this community.