Dietary vitamin D ameliorates hepatic oxidative stress and inflammatory effects of diethylnitrosamine in rats.

The generation of reactive oxygen species (ROS) plays an essential role in the pathogenesis of several diseases. Its implication in inflammation has suggested a possible link between oxidative stress and activation/release of cytokines in precancerous states. Recent observational studies have suggested an association between inflammation and vitamin D deficiency; hence, suggesting that vitamin D could play a role in the pathogenesis of diseases. This study examined the antioxidant and anti-inflammatory potentials of vitamin D in diethylnitrosamine (DEN)-induced oxidative stress and inflammation in rats. Rats were divided into four experimental groups. While groups one and two were administered twice weekly with 30 mg/kg body weight DEN for six weeks, groups three and four were given normal saline. Groups one and three were fed with vitamin D deficient diet, while groups two and four were fed vitamin D diet during the experiment. After that, biomarkers of oxidative stress status were assayed spectrophotometrically. The concentration of inflammatory cytokines was determined using enzyme-linked immunosorbent assay (ELISA). DEN-induced vitamin D deficient diet group had increased antioxidant enzymes' activities. Also, there were elevated concentrations of thiobarbituric acid reactive substances (TBARS) and inflammatory cytokines in the same group. Vitamin D diet, however, reduced oxidative stress effects through the reduction in the activities of TBARS and caused a significant (p < 0.05) increase in nitric oxide concentration. Vitamin D diet significantly (p < 0.05) reduced the level of interleukin 1ß and TNF-α produced in the deficiency state. These findings show that vitamin D may play an essential role in the regulation of hepatic oxidative stress and inflammatory responses.

Preformed volatile nitrosamines in some Nigerian foodstuffs.

Some common Nigerian foodstuffs were assessed for their content of preformed volatile nitrosamine by chemiluminescence detection following gas chromatographic separation. Nitrosodimethylamine levels of between 0.4 and 4.6 ppb were detected in 75% of the samples analysed. The highest value was found in Brassica oleraceae, while Vernonia amygdalina contained the lowest detectable level. These data suggest that Nigerians may be exposed to chronic but very low levels of carcinogenic nitrosamines in their foods.

Potential of endogenous formation of volatile nitrosamines from Nigerian vegetables and spices.

Nitrosatability of dried Nigerian vegetables and spices was investigated under simulated gastric conditions. N-Nitroso-dimethylamine (NDMA) was the only volatile nitrosamine found above the preformed level except in ugwu where N-nitroso-piperidine (2.3 ppb) was also detected. The lowest NDMA value of 0.4 ppb was found in bitterleaf while onions had the highest level (14.7 ppb) of nitrosation. The results suggest that, under endogenous conditions, nitrosation of these foodstuffs could be an important contributory factor in cancer aetiology.

Dietary thiocyanate and N-nitrosation in vivo in the Wistar rat.

The influence of dietary thiocyanate (SCN-) on N-nitrosation in vivo was investigated over 14 min following the administration, by stomach tube, of single doses of sodium nitrite and dimethylamine hydrochloride to male albino Wistar rats whose diet contained appreciable quantities of bound cyanide (cyanogenic glycosides) and free (nonglycosidic) cyanide. The rate of disappearance of the nitrosating agent (NO2-) from the stomach in control animals showed a high linear correlation (r = -0.84) with gastric N-nitrosation, as measured by metabolism (N-demethylation) of 'formed' nitrosamine in liver tissue isolated from these animals. This statistical relationship was significantly increased (r = 0.98), as well as the rate of NO2- utilization and the activity of the N-demethylase enzyme, in animals fed the test diet. Stomach SCN- content was well correlated with both stomach NO2- concentration (r = -0.95) and liver N-demethylase activity (r = +0.93). Interactions, in vivo, between thiocyanate ion and nitrosamine precursors ingested in food may enhance nitrosamine carcinogenesis.

N-nitrosamines and Nigerian habitual drinks, and cancer.

Commercially available samples of Nigerian lager beers and bottled palm wine, and of root cuttings of medicinal plants, assayed for volatile N-nitroso compounds and nitrosatable entities, respectively, by chromatographic, chemiluminescence, colorimetric, derivatisation and nitrosation methods, contained nitrosodimethylamine (0.2-2.3 micrograms/kg; mean, 0.9 micrograms/kg) only in the drinks, and dimethylamine (DMA) and piperidine (1 mg/kg as DMA) in the roots.

Nitrosamine metabolism in kwashiorkor rats.

The in vitro metabolism of nitrosodimethylamine (NDMA) was studied in liver tissue obtained from male weanling kwashiorkor wistar rats. The elimination of this compound and that of nitrosomorpholine (NMOR) from the blood, after a single intravenous dose, was also investigated. N-demethylase activity in liver microsomes of the test animals was not significantly different from that of the controls although the activity of this enzyme per gram wet liver tissue was considerably reduced in the model animals. On the other hand, the glutathione (GSH) content in liver cytosol of the kwashiorkor animals was much higher than that of the controls. The elimination of NDMA and NMOR from the blood of the experimental animals over 8 hr following i.v. administration of the carcinogens, showed that the clearance rate of each nitrosamine was significantly lower in the kwashiorkor rats.

Contamination of some fermented Nigerian beverages by carcinogenic nitrosamines.

A survey to determine the extent of the nitrosamine contamination of some popular fermented Nigerian beverages by dimethyl- and diethylnitrosamine has been carried out in the Lagos, Ogun, Oyo, Ondo, Kwara and Benue States of Nigeria, following the mass spectrometric detection of these carcinogens in palm wine and nono (sour milk). The indication is that the contamination of the drinks, namely, palm-wine, nono, pito, burukutu, and ogogoro, by both nitrosamines is widespread and occurs at the part per billion level. 0.6 - 22 mu g nitrosamine/l was found by routine thin layer and gas liquid chromatographic methods using authentic nitrosamines as reference standards. Because of the widespread contamination of the test beverages by dimethyl- and diethylnitrosamine, and the usually frequent occurrence of nitrosamine precursors in nature, it is presumed that these potent and versatile carcinogens could play a significant role in the formation of human cancers in the Nigerian population.

Microbial nitrosamine formation in palm wine: in vitro N-nitrosation by cell suspensions.

The ability of certain species of bacteria and yeasts that usually contaminate fresh palm sap to induce the formation of the carcinogen dimethylnitrosamine from suitable precursors (trimethylamine, dimethylamine, nitrate, and nitrite) was investigated in vitro under neutral and acid pH conditions. In the incubation media containing cell suspensions of each species of test organism, namely, Aerobacter, Micrococcus, Serratia, Saccharomyces, and two unidentified yeasts and the precursors, added in varying concentrations, the presence of dimethylnitrosamine was indicated. The possible role of indwelling microorganisms in the elaboration of the hazardous compound in fermenting palm wine is discussed.