The hypothesis was proposed that there is a risk of dietary cancer from conditional cancerogens in produce of livestock polluted with irritants of the diterpene ester type, picked up by feeding on species of Euphorbiaceae (spurge). To challenge this, several herbaceous plants of the genus Euphorbia, widespread as weeds and contaminants of livestock fodder, were identified botanically and extracts of their aerial parts were tested for irritancy on the mouse ear. As compared to a standard probe of croton oil, the extracts of E. peplus, E. nubica and E. helioscopia displayed irritancy. The most active extract (that from E. peplus) was investigated by a fractionation procedure monitored by the mouse ear assay, and five molecularly uniform irritant Euphorbia factors Pe1-Pe5 were identified as diterpene ester-type toxins. Together these factors comprise at least 11 ppm in the aerial parts. They were characterized individually to carry the diterpene parent alcohols ingenol, 20-deoxyingenol, and 20-deoxyingenol-6 alpha, 7alpha-epoxide. The irritancy of the aerial plant parts was shown to be caused mainly by the Euphorbia factors Pe1 and Pe2 together. Upon chronic administration of these irritants and hyperplasiogens as principal cancerogenic risk factors in the mouse skin initiation/promotion bioassay, Pe1 and Pe2 were established as tumor promoters. These findings together support the initial hypothesis and suggest the need for further investigations to determine whether there is a consequent risk of dietary cancer.
Sound whole-seed faba beans were treated with (methyl-(14)C) fenitrothion [O, O-dimethyl-O-(3-methyl-4-nitrophenyl) phosphorothioate] at 5 and 10 mg insecticide/kg seeds, a dose normally used in practice. During the 30 weeks of storage period, the penetration and distribution of insecticide residues were studied. The amount of surface residues, internal residues and bound insecticide residues was estimated. Surface residues were found to decrease with the increase in time of storage, whereas internal residues showed a gradual increase with time apparently not dose dependent. Grain-bound residues increased with time and reached to its maximum (14-18%) after 24 weeks of storage. Chromatographic analysis of the internal extracts revealed the presence of the parent compound together with three main metabolites which were found in both free and conjugated form. Feeding mice for 90 days with a diet mixed with total internal fenitrothion residues in stored faba beans led to a reduction in body weight gain, and an appreciable decrease in cholinesterase activity of 32% for plasma and 15% for red blood cells (RBC(S)) after two months of experiment. Also, a significant decrease was showed in both total protein and albumin concentration at the end of feeding period (90 days). Liver and kidney function, as well as lipid profile of treated mice significantly increased at the end of feeding period. After a one-month recovery period, all the examined blood parameters returned to about the control values except blood urea and serum triglyceride.
Anthum graveolens (dill) seeds are a common and very effective household remedy for a wide range of digestive problems. The present study was performed to investigate the effect of dill extracts on altered biochemical parameters in deltamethrin-exposed rats. Deltamethrin was administered orally at doses 7.5 and 15 mg /kg of body weight on the basis of LD 50 for 30 days. The sub-acute toxicity of pyrethroid insecticide deltamethrin varies markedly with the dose employed. Oral administration of plant extracts to rats for 30 days afforded a good protection against deltamethrin elevation in serum marker enzymes. They decreased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) which was increased by DLM administration. Deltamethrin significantly increased the level of plasma total protein (TP), cholesterol and triglyceride. The concentration of urea and creatinine were also increased and all these parameters were decreased by the effect of plant extract. Results were also indicated that, the enzyme activities of acetyl cholinesterase (AchE), catalase (Cat) and glutathione-S-transferase (GST) were increased as compared to the DLM group. Dose dependant of histopathological changes which observed in both liver and kidney are also described.
Special procedures were developed to investigate poisonous milk of lactating goats fed experimentally on aerial parts of the herb Euphorbia peplus L. In extracts of the milk, weakly irritant in the mouse-ear assay, three diterpene ester toxins were detected by techniques of high-performance liquid chromatography. They are of the ingenane structural type: Euphorbia factor Pel (ingenol 20-acetate 3-angelate), Euphorbia factor Pe2 (20-deoxyingenol 3-angelate) and Euphorbia factor Pe4 (20-deoxyingenol-6alpha,7alpha-epoxide 3-angelate). From goats milk collected 15 days after cessation of the experimental feeding period, extracts were completely free of diterpene ester toxins. The toxins polluting the milk are identical to diterpene ester entities occurring in the aerial parts of E. peplus. Of these, Euphorbia factors Pel and Pe2 are known as promoters of tumors of mouse skin. Apart from the toxic Euphorbia factors, the non-toxic parent alcohol ingenol was also detected in the milk. It is absent in the plant, and may have been generated metabolically from a certain portion of the toxic diterpene esters picked up by the goats from their fodder. The results presented here provide, for the first time, data for a novel interpretation of the locally high incidence of esophageal cancer observed in certain areas in the Caspian littoral of Iran, associated with a greater consumption of goat's (and sheep's) milk.
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