A comprehensive evaluation of the toxicology of monogram inks added to experimental cigarettes.

CONTEXT: Cigarettes often have a small identifying mark (monogram) printed either on the cigarette paper toward the filter end of the cigarette or on the tipping paper. OBJECTIVE: A battery of tests was used to compare the toxicology of mainstream smoke from experimental cigarettes manufactured with different monogram inks. Cigarettes with different concentrations of different pigments were compared with cigarettes without ink, and with a control ink. MATERIALS AND METHODS: Smoke from each of the experimental cigarettes was evaluated using analytical chemistry and in vitro bacterial mutagenicity (Salmonella, five strains, ± S9) and cytotoxicity (neutral red uptake) assays. RESULTS: No differences were observed between experimental cigarettes printed with three different pigment loads of iron oxide-based Black pigment and non-printed cigarettes. In general, no dose response was observed. However, increases in certain smoke constituents were found to correlate with Pigment Yellow 14 (also known as benzidine yellow) and Pigment Blue 15 (copper phthalocyanine). Increases in bacterial mutagenicity were observed for high-level print of Pigment Yellow 14 in TA98 and TA1537 and the high-level print of Pigment Blue 15 in TA98. In vitro cytotoxicity of mainstream smoke was unaffected by the presence of monogram ink on cigarettes. CONCLUSION: Statistically significant dose-responsive constituent changes and an increase in mutagenicity were observed with inclusion of Pigment Yellow 14 and Pigment Blue 15. Other pigments showed minimal toxicological activity.

Anti-inflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil.

The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene-, histamine- and bradykinin-induced inflammation. The oil also inhibited arachidonic acid-induced inflammation, suggesting its capacity to inhibit both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail immersion model, the oil raised the pain threshold to a lesser extent than morphine but showed excellent peripherally acting, analgesic activity comparable to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to aspirin. The oil contains 57.38% alpha-linolenic acid. Dual inhibition of arachidonic acid metabolism, antihistaminic and antibradykinin activities of the oil could account for the biological activity and the active principle could be alpha-linolenic acid an omega-3 (18:3, n-3) fatty acid.

[Oral toxicity at 60-days of sacha inchi oil (Plukenetia volubilis L.) and linseed (Linum usitatissimum L.), and determination of lethal dose 50 in rodents]. / Toxicidad oral a 60 días del aceite de sacha inchi (Plukenetia volubilis L.) y linaza (Linum usitatissimum L.) y determinación de la dosis letal 50 en roedores.

OBJECTIVES: To evaluate the oral toxicity at 60 days and to determine the lethal dose 50 (LD 50) of raw sacha inchi (Plukenetia volubilis L.) and linseed (Linum ussitatisimum) oils in Holtzman rats and mice of the strain Balb C57 respectively. MATERIALS AND METHODS: For the evaluation of the oral toxicity of repeated doses for 60 days, 24 male Holtzman rats were used, divided in three groups of 8 each, the groups were: physiologic saline solution 4 mL/kg (FSS), sacha inchi oil 0.5 mL/kg (SI05) and linseed oil 0.5 mL/kg (L05), during the experiment the body weight was controlled weekly, and signs of toxicity in the research groups, as well as total cholesterol, HDL, glucose, triglycerides and alkaline phosphatase at days 30 and 60 after initiating the experiment. For the evaluation of the LD50 male mice of the Balb C57 strain were used in groups of 10 animals, and they were administered increasing oral doses of raw oils until reaching 1 mL/kg (37 g/kg). RESULTS: The serum parameters in the rats indicated there is no toxicity at 60 days and that the administration of the oils lowered the levels of cholesterol, triglycerides and increased the HDL in comparison with the control group. The LD50 shows that the raw sacha inchi and linseed oils have doses above 37 g/kg of body weight. CONCLUSIONS: Sacha inchi and linseed oils are harmless at 60 days and present a LD50 above the 37 g/kg of animal.

Flaxseed oil-trastuzumab interaction in breast cancer.

Flaxseed oil (FO), which is rich in n-3 fatty acid, is commonly consumed by breast cancer patients because of its potential anti-cancer effects. Trastuzumab (TRAS) is the primary drug for epidermal growth factor receptor 2 (HER2) positive breast cancer. We investigated in athymic mice whether combining dietary FO (8%) with TRAS treatment (2.5 or 5mg/kg body weight) can cause better or adverse effect on established human breast tumors overexpressing HER2 (BT-474). Control tumors significantly grew 187%, TRAS2.5 treated tumors did not change, while TRAS5, FO+TRAS2.5 and FO+TRAS5 treated tumors significantly regressed 75%, 89% and 84%, respectively, after 4weeks treatment. Two weeks after stopping TRAS treatment while continuing on same diet, tumor size in FO+TRAS2.5 group was 87% lower than in TRAS2.5 group and was not different from TRAS5 group with or without FO. Combined TRAS2.5 treatment with FO caused a significantly lower tumor cell proliferation and higher apoptosis compared to TRAS2.5 treatment alone and showed similar effect to TRAS5 treatment with or without FO. Hence, FO did not interfere with TRAS but rather enhanced its tumor-reducing effects and combined FO and low dose TRAS was as effective as high dose TRAS treatment.

Accelerative effect of olive oil on liver glycogen synthesis in rats subjected to water-immersion restraint stress.

The effects of dietary oils on stress-induced changes in the liver glycogen metabolism of male Wistar rats at 6 weeks of age were investigated. The rats were subjected to repetitive water-immersion restraint and fed with a 20% saturated fatty acid mixture (PSC), olive oil (OLI), safflower oil (SAF), or linseed oil (LIS) diet. Stress loading decresed the body weight gain, although the food intake was hardly changed, and the weights of the liver and spleen generally declined regardless of the elapsed time after stress loading and the type of dietary oil. The adrenal weight was generally enhanced by stress in all deitary groups, and particularly tended to be greater in the OLI and PSC groups than in the other two. The plasma corticosterone concentration increased immediately after stressing (Stress-1), but approached the level of the rats with no stress (No stress) 2 h after releasing the stress load (Stress-2) in all groups. The enhancement of corticosterone level in the Stress-1 animals was large in the PSC and OLI groups, and the decline of this level in the Stress-2 animals was small in the OLI group when compared with the other groups. Although the concentrations of total cholesterol (T-CHOL) and triacylglycerol (TG) in the plasma were decreased by stress loading in all groups, these concentrations in the PSC and OLI groups were nearly always higher than in the other groups. The liver serine dehydratase (SDH) activity enhanced by stress was high in the OLI group and tended to be high in the PSC group when compared with the other groups. The contents of liver glycogen were reduced in the Stress-1 animals and extremely elevated in the Stress-2 animals of all groups, and particularly in the OLI group, the reduction in the Stress-1 animals was smaller and the enhancement in the Stress-2 animals was greater than in the other groups. These results suggest that feeding oleic acid to rats exposed to water-immersion restraint further accelerated liver glycogen synthesis through the rise in liver SDH activity due to increased corticosterone secretion when compared with the effect from linoleic and alpha-linolenic acids.

[Influence of heated linseed oil on reproduction in the female rat and on the composition of hepatic lipids in young rats]. / Influence d'huiles de lin chauffées sur la reproduction chez la ratte et sur la composition des lipides hépatiques des jeunes

During gestation and lactation, six month old female Wistar rats were fed diets containing 10 p. 100 by weight of various vegetable oils; thermopolymerized linseed oil at 275 degrees C for 12 hours under nitrogen atmosphere (group T), oxidized linseed oil at 200 degrees C for 100 hours under air atmosphere (group O). The two oils contain respectively 11,5 and 1,1 p. 100 of cyclic monomers (18 C). Control groups were fed either fresh linseed oil or fresh peanut oil under the same conditions. In group T, most of the newborn rats die at birth or during the first three days of life; none of them survive 13 days after birth. In group O, mortality of youngs is not so high but is still significantly higher than in control groups. Moreover, dead young rats of group T have heavier livers and higher lipid content in the organ. Cyclic monomers were detected in liver fatty acids. In surviving young rats of group O,the body growth during lactation is significantly slower than in control animals. Young rats of group O were sacrificed at the age of 14 days. Liver weight and lipid content of the organ are increased and cyclic monomers were detected. The effects are however less pronounced than in group T. One can assume that among abnormal compounds formed during heating of linseed oil, cyclic monomers are responsible for the toxic effects observed in the present experiment since they have been transmitted to the litters either during gestation or lactation.