Olumbe Bassir

Oxidative metabolism of aflatoxin B1 by mammalian liver slices and microsomes.

Abstract The metabolism of aflatoxin B 1 in mammals involves both hydroxylation and demethylation. The species differences in the metabolism of aflatoxin B 1 in demethylation and hydroxylation have been investigated. The differences in the metabolism of the toxin are due principally to differences in enzymic action of microsomal enzymes. Aflatoxin B 1 is metabolized relatively slowly in the liver tissues of dog, rat and sheep than in the mouse, goat, guinea pig, rabbit and golden hamster. Also the sheep demethylates aflatoxin B 1 poorly but the dog does not demethylate the toxin. Differences also exist in the hydroxylation of the toxin; of all the mammals studied, only the mouse does not produce aflatoxin M 1 .

The conjugation of phenol, benzoic acid, 1-naphthylacetic acid and sulphadimethoxine in the lion, civet and genet.

In the domestic cat (FeZis catus) phenol is converted mainly to phenylsulphate with only small amounts of phenylglucuronide [l] . The cat’s ability to form the glucuronides of foreign compounds is low compared with other species [2] and it forms little or no glucuronide with phenol [I], benzoic acid [3], sulphadimethoxine [4] , or 1-naphthylacetic acid [5]. It was of interest therefore to find out whether catlike animals were similar to the domestic cat. The above four compounds were administered to weaned lion cubs (Panthera Zeo) and adult African civets (Viverra civet&) and forest genets (Genetru par&m) and their urine examined for metabolites. These animals showed little or no glucuronide formation with these compounds and they excreted phenol almost entirely as phenylsulphate, benzoic acid mainly as hippuric acid, 1-naphthylacetic acid as the glycine conjugate and sulphadimethoxine as such and as the N4-acetyl derivative. As far as conjugation is concerned, these compounds behave in the lion, civet and genet much as they do in the domestic cat.

Drug metabolism in ”exotic” animals

SummaryMost studies of foreign compound metabolism have been performed in a restricted number of common laboratory animal species. The examination of animals not commonly found in the laboratory may aid in understanding the effects of environmental chemicals on wild animals and in the search for better animal models for human drug metabolism. We have performed a number of studies in “exotic” animals, such as the lion, civet, genet, hyena, elephant, various bats and reptiles, and this review compares the findings with those in common laboratory animals, to explore the possibility that drug metabolism studies may aid in the zoological classification of animals.

Effects of aflatoxin B1 on the swelling and adenosine triphosphatase activities of mitochondria isolated from different tissues of the rat

Although the cells most affected in aflatoxin poisoning are those around the portal vein and bile duct [l] it has also been reported [2,3] that the mitochondria of rat liver cells are vulnerable to aflatoxin. Not all tissues respond in the same degree to the in vivo administration of aflatoxin. Wogan and his coworkers [4, 51 investigated the distribution of a single-dose injection of [ 14C]aflatoxin in the rat and found that high concentrations occurred in the liver, considerably smaller amount in the kidney and negligible amounts in the heart and the testis. There seemed to be no published quantitative data on the biochemical functions of mitochondria in the presence of atlatoxin. Therefore, it appeared to us desirable to obtain information on the in vitro osmotic behaviour of mitochondria from various tissues. In view of the involvement of adenosine triphosphatase (ATPase) in processes of energy conservation, we have also investigated the effect of aflatoxin on mitochondrial ATPase activities in the liver, kidney, heart and testis.

The uncoupling effect of N-(phosphonomethyl)glycine on isolated rat liver mitochondria.

Abstract The rates of oxygen consumption by rat liver mitochondria, respiring on either succinate, a two-site substrate, or β-hydroxybutyrate, a three-site substrate, and in the presence of varying concentrations of the isopropylamine salt of N -(phosphonomethyl) glycine (PMG) have been measured polarographically. The respiratory control ratios of these mitochondria were shown to be significantly reduced, by at least 10 per cent by the addition of 3.95 × 10 −5 M PMG. There was a larger decrease in these ratios, up to 50 per cent, as the concentration of the herbicide was raised to 1.25 × 10 −3 M. At concentrations ranging from 3.12 × 10 −4 M to 1.25 × 10 −3 M, PMG restored respiration of mitochondria previously inhibited by oligomycin. Adenosine triphosphatase (ATPase) activity was enhanced by the addition of PMG. In this respect, the maximal increase, 3-fold, was obtained at 6.25 × 10 −4 M PMG. These findings suggest that N -(phosphonomethyl) glycine uncouples oxidative phosphorylation in isolated rat liver mitochondria.

Two new metabolites of Aspergillus flavus (Link)

About a dozen different fluorescent substances have been isolated from cultures of Aspergillus flaws (Link) in natural and synthetic media by Smith and McKernam [l] and by Asao, Buchi et al. [2] . Only the aflatoxins B,, B,, G,, G, and three related quinones have been reported as being toxic. We therefore decided to investigate the nature and toxic properties of two substances previously referred to as fractions 10 and 11 by Smith and McKernam [ 1 ] . It is shown in this report that these substances may be purified as crystalline, unsaturated fatty acids. The substance B, which gives a blue fluorescence is as toxic to chick embryo as aflatoxin B, while that which gives a green fluorescence in ultraviolet light (Go) is as toxic as aflatoxin G,.

Alterations in function, enzyme activities, and histopathology of the liver of the rat after administration of phytohemagglutinins (Lectins)

Abstract The administration of phytohemagglutinins (lectins) to rats induced impairment of liver function, activation of some dehydrogenase enzymes connected with carbohydrate metabolism, and finally coagulative necrosis of the liver. Some of the lectins elicited more severe biochemical changes than others. However, the histopathological alterations were similar in all cases.

Effects of phytohemagglutinins from immature legume seeds on the function and enzyme activities of the liver, and on the histopathological changes of some organs of the rat

Abstract Toxic phytohemagglutinins (lectins) were detected in some half-matured edible legume seeds. Studies were conducted to evaluate the effects of these lectins on liver function, ATPase, fumarase, and dehydrogenase activity in the rat. Histopathological alterations caused by these lectins on some organs of the animals were also monitored. Generally, these lectins induced marked toxic effects. It is therefore suggested that these young edible legume seeds be thoroughly processed before eating to prevent toxicological hazards. Grazing livestock probably should be prevented from eating these immature legume seeds.

Conjugation of foreign compounds in the elephant and hyaena

Little is known about the metabolism of foreign compounds in exotic animals. French et al. [ 1 ] have examined lions, genets and civets and Ette et al. [2] and Idle et al. [3] have studied the Indian fruit bat. In this paper we report some observations made on the African elephant (Loxodonta) and the spotted hyaena (Crocuta crocutu). There is a report in the literature that the elephant (Indian?) forms hippuric acid [4], but no data seems to have been obtained on the hyaena. In this work it will be shown that like most species of mammals, the African elephant converts benzoic and phenylacetic acid into their glycine conjugates and phenol into its sulphate and glucuronic acid conjugates. In the case of the hyaena phenol, at a level of 10 mg/ kg, forms only sulphate conjugates and is thus similar to the cat, lion, civet and genet and also the caracal [5]. The hyaena also does not acetylate the aromatic amino group of sulphadimethoxine and is in this respect like the domestic dog [6] rather than the cats which acetylate the drug [ 1 ] . The hyaena, however, converts phenylacetic acid to phenacetylglycine like many other species. 1-Naphthylacetic acid is conjugated in the hyaena mainly with glycine and to a lesser extent with taurine as it is in both the cat [7] and the dog [8], but there is also a substantial glucuronide conjugation of this acid in the hyaena which does not occur in the cat [7] and only slightly in the dog 181. 2. Experimental

A comparative assessment of toxic effects of dimethylnitrosamine in six different species

The hepatotoxicity which usually accompanies the oral administration of dimethylnitrosamine (DMN) to laboratory animals was studied in male rats, guinea pigs, cats, lizards, ducks, and monkeys. A single dosage of 50 mg/kg, which is necrotizing to rat liver, in most cases produced within 30 hr more acute liver damage in cats than in guinea pigs, rats, or monkeys, in that order of susceptibility, but was not toxic to lizards or ducks. DMN (5 mg/kg), given daily, induced the same degree of liver damage in guinea pigs and rats as did a single dose of the same compound. However, in cats and monkeys the effect of a single dose of 50 mg/kg was less severe than that obtained after the administration of 5 mg/kg over a period of 5–11 days. DMN (1 mg/kg), administered daily over a period of 30 days, was particularly harmful to cats and lizards. Clinicopathologic signs of overt toxicity were also monitored. Our results would support the view that species differences and dosage rates are both critical factors determining the different susceptibilities of various animals to nitrosamine toxicity.