Polycyclic aromatic hydrocarbon burden in ambient air in selected Niger Delta communities in Nigeria.

The Niger Delta area in Nigeria has major oil producing and refining centers that characterized enormous industrial activities, especially in the petroleum sector. These industrial processes release different kinds of atmospheric pollutants, of which there is paucity of information on their levels and health implications. The objective of this study was to determine the ambient levels of polycyclic aromatic hydrocarbons (PAHs) in communities of a local government area (Eleme) where oil wells, petrochemical installations, a refinery, and a fertilizer complex are located. Respirable particulate matter (PM) in air were collected using Anderson high-volume sampler with PM with aerodynamic diameter > 10 microm (PM10) inlet for collecting filterable, particle-bound PAHs according to standard methods. PAHs were analyzed following standard methods for the 16 World Health Organization (WHO) prioritized components. The results were compared against the levels in another local government area (Ahoada East) with low industrial presence. The average total PAH concentration in Eleme of 9.2 microg/m3 was among the highest in the world; by contrast, the average concentration in Ahoada East was only 0.17 ng/m3. The most prominent PAHs at Eleme were those known to be carcinogenic and included benzo(a)pyrene (1.6 x 10(4) ng/m3 at bubu), benzo(k)fluoranthene (2.4 x 10(4) ng/m3 at Akpajo where a petrochemical is located), pyrene (3.1 x 10(3) ng/m3 at Ogale), and indeno(1,2,3-cd)pyrene (9.1 x 10(3) ng/m3 at Akpajo). Data from this study emphasize the need for a comprehensive source apportionment study and an assessment of the health effects of oil production on local communities of Nigeria where no such information currently exists.

The effect of modulation of glutathione levels on markers for aflatoxin B1-induced cell damage.

The modulatory effect of glutathione levels on markers for aflatoxin B1 (AFB1)-induced cell damage has been investigated in the rat (susceptible specie) and the (mouse resistant specie). The concentration of GSH was depleted and increased by administering paracetamol (PAM) and cysteine respectively and activities ofglutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) were determined. The effect ofAFB1 on hepatic lipid peroxidation in both species was also investigated. Treatment of rats with 2 mg/kg.bwt AFB1 intraperitoneally caused a depletion of GSH in the liver to a minimum at 6 h (80% of the control value) and the level returned to normal after 24 h. GST was similarly increased to a maximum at 6 h and the level also returned to normal after 24 h. GSH and GST activities were not significantly affected in AFB1-treated mice. Orally administered PAM (400 mg/kg.bwt) caused a depletion of GSH with a minimum at 6 h (59% and 36% of the control rats and mice respectively). Pretreatment of AFB1 with PAM produced a serious depletion at 6 h (34% and 35% of the control rats and mice respectively). GST activities were also marginally increased in both animals. AFB1 pretreatment mediated (P < 0.001) hepatic lipid peroxidation in rats but not in mice as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Treatment of rats and mice with oral cysteine (50 mg/kg bwt) elicited a significant elevation of GSH. Administration of cysteine with AFB to rats attenuated the toxic effects of AFB1 on GSH and inhibited the formation of TBARS. gamma-GT activity was significantly increased when AFB1 alone was administered to rats but was not increased (P > 0.05) when cysteine was pretreated alone with AFB1. Combined treatment of AFB, and PAM induced 177% increase in gamma-GT activity. Overall, our results suggest that the metabolism of aflatoxin B, by GSH does not lead to the formation of toxic products but rather GSH plays a protective role in AFB1-induced cell damage and GSH pathway is less utilised in mice.

Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds.

The chemopreventive effects of kolaviron, a natural antioxidant bioflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats. Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase (gamma-GT) by 62%, 56% and 72% respectively. Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1-treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and gamma-GT as well as lipid peroxidation caused by AFB1 (P<0.01). Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively. In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P<0.01). Pretreatment of rats with kolaviron, vitamins C and E alone did not exert genotoxicity assessed by the formation of micronucleated polychromatic erythrocytes (MNPCEs) (P>0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P<0.001) after 72 h. While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemopreventive agent against AFB1-induced genotoxicity and hepatic oxidative stress. Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.

Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats.

1. The hypolipidaemic effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria, was investigated in rats. The ability of Questran (Bristol-Myers Squibb, Hounslow, UK), a hypolipidaemic therapeutic drug, to attenuate hypercholesterolaemia in rats was also examined. 2. In order to assess the hypolipidaemic effect of this extract in experimental animals, thiobarbituric acid-reactive substances (TBARS), cholesterol, phospholipid, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglyceride levels were determined in the plasma and liver. 3. Cholesterol administered orally to rats at a dose of 30 mg/0.3 mL five times a week for 8 consecutive weeks resulted in a significant increase (P<0.001) in the relative weight of the heart of hypercholesterolaemic animals compared with control. However, cotreatment with kolaviron and Questran ameliorated the cholesterol-induced enlargement of the heart. Kolaviron (100 and 200 mg/kg) elicited 88.5 and 87.4% reductions, respectively, in plasma cholesterol levels of pretreated animals compared with the cholesterol-fed group. In addition, kolaviron produced a significant decrease (P<0.05) in post-mitochondrial fraction (PMF) cholesterol levels in treated animals compared with untreated hypercholesterolaemic animals. Similarly, Questran significantly decreased (P<0.05) the cholesterol-induced increase in plasma cholesterol levels compared with untreated hypercholesterolaemic animals. In addition, (100 and 200 mg/kg) significantly (P<0.05) decreased plasma LDL-C levels by over 70% in treated animals compared with untreated hypercholesterolaemic animals. Similarly, kolaviron significantly decreased (P<0.05) PMF LDL-C levels by over 60% in treated animals compared with untreated hypercholesterolaemic animals. 4. The significantly (P<0.05) higher values of plasma and PMF triglycerides obtained in cholesterol-fed animals compared with control animals were unaltered following cotreatment with kolaviron and Questran. In the present study, there was a significant decrease (P<0.05) in plasma formation of malondialdehyde in kolaviron- and Questran-treated animals compared with untreated hypercholesterolaemic animals. 5. The results of the present study demonstrate that kolaviron exerts a hypocholesterolaemic effect and reduces the relative weight of the heart in cholesterol-fed animals. This reduction and the favourable lipid profile indicate a possible anti-atherogenic property of the extract.

Concentrations of copper, iron, and zinc in the major organs of the wistar albino and wild black rats: a comparative study.

The concentrations of copper, iron, and zinc in the major organs of Wistar albino (Rattus norvegicus) and wild black rats (Rattus rattus) were measured by means of atomic absorption spectroscopy. The copper levels in the kidneys and liver of the Wistar albino rats (WARs) were significantly higher (p<0.05) than in the wild black rats (WBRs). There were no significant differences in the concentrations of zinc in the liver, lungs, kidneys, and brain between the two study groups, but zinc was significantly higher in the spleen (p<0.05) and lower in the heart (p<0.05) of WAR, compared to WBRs. Iron was significantly higher (p<0.05) in the heart and spleen of WBRs, compared to WARs. There were no extreme differences in the organ concentrations of trace elements between the two species, but, cumulatively, the WARs tend to have higher metallic concentrations in their system than the WBRs. The potential of these differences on the experimental results should not be overlooked and will serve as basis to further consider the complex interrelationships of these animals in their microenvironments and macroenvironments.

Inhibition of aflatoxin B1 genotoxicity in human liver-derived HepG2 cells by kolaviron biflavonoids and molecular mechanisms of action.

Kolaviron biflavonoids have demonstrated antihepatotoxic activity in animal studies. The present study investigated the possible chemopreventive potential of kolaviron in inhibiting aflatoxin B1 (AFB1) genotoxicity in HepG2 cells. Kolaviron inhibition of AFB1-induced cytotoxicity by clonogenic assay and genotoxicity by [3H]thymidine incorporation in unscheduled DNA synthesis were evaluated, including antioxidant potential of kolaviron determined by its reduction in the intracellular reactive oxygen species level induced by hydrogen peroxide. Induction of AFB1-detoxicating enzymes such as cytochrome P450 3A4 (3A4) and glutathione S-transferases (GSTs) A1-1/ A2-2 (alpha) and M1B (mu) was determined by reverse transcription polymerase chain reaction (RT-PCR) and northern blotting for the messages and western immunoblot analysis for protein. Kolaviron significantly (P < 0.01) and dose-dependently inhibited the cytotoxicity (by 71.6%) and genotoxicity (47.1%) of AFB1 in HepG2 cells. The antioxidant potential of kolaviron compared favourably with values for the standard antioxidant trolox C (53.8% at only 4.5 x 10(-2)-fold kolaviron concentration) but was below that of butylated hydroxyanisole (58.1% at a ninefold kolaviron concentration). It induced about threefold increases in the messages for 3A4 and GSTs alpha and mu, including a twofold increase in GSTalpha protein. Kolaviron may have chemopreventive potential in inhibition of human AFB1 genotoxicity and possibly hepatocarcinogenesis.

Effect of three structurally related antimalarial drugs on liver microsomal components and lipid peroxidation in rats.

Changes in microsomal drug oxidizing enzymes, microsomal lipids, hepatic glutathione (GSH), glutathione S-trans-ferase (GST) and malondialdehyde (MDA) formation following administration of rats with therapeutic doses of three structurally related antimalarial drugs, amodiaquine (AQ), mefloquine (MQ) and halofantrine (HF) were investigated. There was a significant decrease in the activities of aniline hydroxylase, p-nitroanisole O-demethylase and pentoxyresorufin O-dealkylase in AQ, MQ and HF treated rats. AQ elicited the greatest effect with 50, 37 and 67% reductions in the activities of aniline hydroxylase, p-nitroanisole O-demethylase and pentoxyresorufin O-dealkylase, respectively. All the drugs prolonged hexobarbital-sleeping time to varying extents. The three drugs increased significantly the cholesterol per phospholipid ratio. AQ, MQ and HF decreased significantly the GSH level, GST activity and increased the formation of MDA. The results indicate that the alterations in hepatic microsomal components and lipid peroxidation caused by the antimalarials are related to the structural differences in the compounds.

Chloramphenicol and ampicillin-induced changes in rat hepatic esterase and amidase activities.

The influence of ampicillin and chloramphenicol administered intraperitoneally singly or in combination on the protein content and the activities of hepatic esterase and amidase have been investigated in rats. The results have been compared to the effects of phenobarbitone (inducer) and p-nitrophenyl-phosphate (inhibitor) of hepatic hydrolases. Ampicillin pretreatment reduced protein level and amidase activity by 3.5% each but caused a significant increase (8.1%) in total esterase activity compared to controls. Chloramphenicol treatment caused an overall decrease in protein level, esterase and amidase activities respectively by 11%, 11%, and 35% over controls. Combined administration of both drugs resulted in a decrease in protein, esterase and amidase activities by 11.5%, 12.5%, and 41.2% respectively, thus mimicking the effects obtained with chloramphenicol alone. The changes induced by administration of the drugs particularly in combination on the constituent enzymes of rat hepatic hydrolases may affect the ability of the body to deal with exposure to environmental chemicals if extrapolated to man.

Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron--a Garcinia kola seed extract.

The effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria on hepatotoxicity and lipid peroxidation induced by 2-acetylaminofluorene (2-AAF) in rats was investigated. The ability of butylated hydroxyanisole (BHA) to attenuate the toxic effect of 2-AAF was also examined. Kolaviron administered orally to rats at a dose of 100mg/kg body weight twice a day for 1 week before challenge with 2-AAF (200mg/kg feed) and continuously for 3 weeks at a single dose of 200mg/kg body weight reversed the 2-AAF-mediated decrease in final body weight and relative organ weights, especially the liver. BHA was administered at a dose of 7.5g/kg feed to the animals for 4 weeks. The extract decreased significantly the 2-AAF-mediated increase in the activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and ornithine carbamyl transferase by 58%, 62%, 60% and 67%, respectively. BHA elicited respectively 55%, 63%, 57% and 65% reduction in the 2-AAF induced-increase in the activities of these enzymes. Histological examination of the liver slices correlated with the changes in serum enzyme alterations. Similarly, kolaviron decreased the 2-AAF reduction of 5'-nucleotidase and glucose-6-phosphatase activities by 63% and 60%, respectively while BHA elicited 59% and 61% decrease in the activities of these enzymes. Simultaneous administration of kolaviron with 2-AAF inhibited microsomal lipid peroxidation as assessed by the thiobarbituric acid reacting substances (TBARS) formation by 66%. BHA produced a 64% reduction in TBARS formation. In the present study, kolaviron appears to act as an in vivo natural antioxidant and an effective hepatoprotective agent and is as effective as BHA.

Modulation of carbon tetrachloride-induced lipid peroxidation and xenobiotic-metabolizing enzymes in rats fed browned yam flour diet.

The modulatory effect of browned yam flour diet, a dietary, staple in south-western Nigeria, on carbon tetrachloride (CCl4)-mediated lipid peroxidation and on the activities of liver microsomal and cytosolic enzymes was studied in male rats. Browned yam flour diet fed at the level of 25% and 50% to rats for 5 weeks significantly reduced the lipid peroxidation induced by CCl4 (0.5 ml/kg/wk) administered two weeks after starting the animals with the diets. The diets elicited 62% and 79% reductions in CCl4-mediated peroxidation, respectively, in the absence of exogenously added oxidants. The activities of microsomal aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), pentoxyresorufin-O-dealkylase (PROD) and cytosolic GSH S-transferase (GST) were increased when rats were fed the 25% or 50% browned yam flour diets. Browned yam flour fed at the level of 25% to rats decreased the CCl4-mediated reduction in the activities of microsomal AH, APD, PROD and GST by 64%, 28%, 58% and 25%, respectively, and by 82%, 48%, 83% and 55% when rats were fed with 50% of the diet. The results suggest that browned yam flour diet could protect against chemically-mediated lipid peroxidation and tissue damage possibly by scavenging chemically generated reactive species and enhancing carcinogen-detoxifying system.

Hepatic drug metabolizing enzyme induction and serum triacylglycerol elevation in rats treated with chlordiazepoxide, griseofulvin, rifampicin and phenytoin.

Five days intraperitoneal administration of rats with chlordiazepoxide (0.4 mg/kg), griseofulvin (7 mg/kg), rifampicin (8. 6 mg/kg), phenytoin (4.3 mg/kg) and phenobarbitone (1.4 mg/kg; an established inducer of microsomal enzymes) caused a significant increase in serum triacylglycerol (P<0.001) and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase (P<0.001). Aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase activities were increased 1.48-, 1.15- and 1.47-fold, respectively, in chlordiazepoxide-treated rats, 1.65-, 1.20- and 1.38-fold in griseofulvin-treated rats, 1.74-, 1.36- and 1.44-fold in rifampicin-treated rats, 1.56-, 1.29- and 1.62-fold in phenytoin-treated rats and 2.26-, 1.72- and 1.93-fold in phenobarbitone-treated rats. Chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone increased the activity of cytosolic phosphatidate phosphohydrolase by 52, 58, 67, 73 and 82%, respectively, while the drugs elicited 50, 60, 60, 73 and 87% increases in the activity of the microsomal phosphatidate phosphohydrolase. Similarly, chlordiazepoxide, griseofulvin, rifampicin, phenytoin and phenobarbitone elicited 2.4-, 2.39-, 2.34-, 1.69- and 3.75-fold increases in serum triacylglycerol concentrations. The correlations between serum triacylglycerol concentrations and the activities of aniline hydroxylase, aminopyrine N-demethylase and p-nitroanisole O-demethylase were significant in all treatment groups (r=0.83, r=0.92 and r=0.87, respectively, n=30, P<0.001). Our results suggest that induction of hepatic enzymes by the administered drugs may lead to hypertriglyceridaemia as an adverse effect, possibly by inducing the activity of regulatory enzymes in the biosynthesis of triglyceride.

Possible modulatory effect of browned yam flour diet on chemically-induced toxicity in the rat.

The possible modulatory effect of browned yam flour, a local dietary staple in south western Nigeria, on the toxicity of 7,12-dimethylbenzanthracene (DMBA), 3-methylcholanthrene (3-MC), carbon tetrachloride (CCl4) and bromobenzene (BrB) in rats was investigated. Feeding rats with 25% browned yam flour 2 wk before treatment with 65 mg/kg DMBA (single dose) and 5 mg/kg 3-MC and continued for 3 wk significantly decreased the reduction in final body weight or weight gain and organ weights caused by the two compounds. Similarly, the diet decreased the reduction in body weight or weight gain and the increase in relative liver weight mediated by oral treatment with 0.5 ml CCl4/kg and 2.5 mmol BrB/kg body weight. Incorporation of 25% browned yam flour into rat diet significantly reduced the DMBA-mediated decrease in haemoglobin content, packed cell volume, red blood cell count and white blood cell count by 7, 5, 20 and 10%, respectively; while the diet reduced the 3-MC-mediated decrease in these parameters by 15, 28, 9 and 17%, respectively. The same diet elicited 23, 45, 13 and 33% decreases in CCl4 mediated reduction in these parameters and 23, 18, 16 and 29% in the case of BrB. Browned yam flour diet caused 10, 14 (P < 0.001) and 4% (P < 0.05) reductions in the DMBA-mediated increase in serum aspartate aminotransferase, alanine aminotransferase and serum alkaline phosphatase, respectively; and 32, 31 (P < 0.05) and 13% (P < 0.001) in the case of the 3-MC-mediated increase. Also, the diet reduced CCl4-mediated increase in the activities of these by 40, 34 and 31%, respectively and by 23, 30 and 29% following BrB treatment. These results suggest that browned yam flour diet could possibly be a modulator of chemically induced toxicity.

Covalent binding and glutathione depletion in the rat following niridazole (ambilhar) pretreatment.

In vivo and in vitro studies with rats have shown that (14C) niridazole (Ambilhar) binds covalently to tissue proteins, but not to nucleic acids. In the in vitro experiments, binding required the presence of NADPH in the incubation medium, suggesting the production of an active metabolite via a cytochrome P-450-mediated reaction. Niridazole also caused significant dose-dependent decreases in liver and kidney glutathione levels, even though it had no apparent effect on blood glutathione. Alteration of tissue glutathione availability by pretreatment with chloracetamide or cysteine respectively either increased or decreased the NADPH-dependent covalent binding. Pretreatment with phenobarbital, 3-methylcholanthrene or cobaltous chloride, which change the rate of metabolism of (14C) niridazole, similarly altered the extent of protein binding. It is shown that the decrease in tissue glutathione concentration is not due to an effect of the drug on the activities of either glucose-6-phosphate dehydrogenase or glutathione-S-transferases. However, there is a significant reduction in glutathione reductase activity in all the tissues studied. The possible relationships between the results obtained and the cytotoxic effects of niridazole have been discussed.

Drug induced alterations in some rat hepatic microsomal components: a comparative study of four structurally different antimalarials.

Alterations in microsomal drug metabolizing enzymes, microsomal lipids and some serum enzymes following pre-treatment of rats with therapeutic doses of four structurally different antimalarial compounds, chloroquine (CQ), quinine (Q), quinacrine (QK) and primaquine (PQ) have been investigated. CQ and Q significantly decreased the activities of aminopyrene N-demethylase, aniline hydroxylase and both microsomal and cytosolic glutathione S-transferases. Only aniline hydroxylase was markedly decreased by QK, while PQ did not have much effect on any of these enzymes. CQ, Q and QK significantly increased the cholesterol:phospholipid ratio while all four compounds decreased the phosphatidyl choline:sphingomyelin (PC/S) ratio. All the drugs increased the activities of the serum enzymes glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and alkaline phosphatase. The possible relationships of these results to structural variations in the four drugs being investigated has been discussed.

Effect of dietary vitamin E (alpha-tocopherol) on aflatoxin B metabolism.

Intraperitoneal injection of rats with 2 mg/kg ring labelled 14C AFB1 (spec. act. 110 mCi/mM/nmole) showed a higher level of radioactivity in the urine of test animals on diets containing 600 mg/kg vit. E 24 h after pretreatment. Analysis of the urine by chloroform extraction, thin layer chromatography and liquid scintillation counting of the various fractions showed less aflatoxin M1 (AFM1) and less unmetabolized AFB1 in test samples than in controls. Incubation of ring labelled 14C AFB1 with hepatic 10,000 g supernatant fractions, however, showed increased metabolism of AFB1 by fractions from test animals as compared with the controls. Rate of disappearance of 14C AFB1 and the consequent formation of AFM1 was greater in the test fractions than in the controls. At 30 days all test animals showed higher levels of serum vitamin E than the controls. Hepatic aniline hydroxylase and ethyl morphine N-demethylase activities of the liver fractions and blood glutathione reductase activity were greater in the tests. P-nitroanisole-O-demethylase activity was reduced while hepatic and serum reduced glutathione levels remained basically unaltered.

Covalent binding of niridazole (Ambilhar) to tissue proteins of the rat.

In vivo and in vitro experiments have shown that [14C] niridazole ( NDZ ) can covalently bind to the proteins of rat liver, kidney and testes, but not to the DNA in these tissues. The covalent binding was dose dependent, and the greatest amount of binding was found in the microsomal fraction. The binding of [14C] NDZ to microsomal protein was linear with time and with protein concentration. Reduced nicotinamide adenine dinucleotide phosphate was necessary for the binding, while cobaltous chloride pretreatment inhibited it, demonstrating that a cytochrome P-450 dependent mixed function oxidase mediated the binding. Pretreatment of rats with other compounds, such as phenobarbital, 3-methyl-cholanthrene and chloracetamide which alter the rate of metabolism of [14C] NDZ similarly affected the extent of hepatic binding of the radiolabelled metabolite. The possible relationships between these results and the cytotoxic effects of NDZ have been discussed.

Response of the rat's hepatic drug-metabolizing enzyme system to chemotherapy of Trypanosoma b. brucei infections with Berenil and Suramin.

Berenil (4,4-diamidinodiazoaminobenzene-diacetamide acetate) or Suramin [sodium salt of 8-(3-benzamido-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid] treatment of rats infected with Trypanosoma b. brucei enhanced hepatic microsomal aniline hydroxylase and p-aminopyrine N-demethylase activities. While Suramin inhibited significantly the activities of cytoplasmic glutamate dehydrogenase and lactate dehydrogenase, Berenil had no effect. The kinetic profiles of these enzymes consistently showed a Km value similar to that of controls. Both cytosolic and microsomal glutathione-S transferase and microsomal epoxide hydratase were unaffected by Suramin. However, a significant increase in cytosolic glutathione-S transferase was observed with Berenil. Microsomal phospholipids were not affected by any of the drugs.

Effect of 1.1.1 trifluoro-N-(2-methyl-4-phenyl sulfonyl) methane sulfonamide (Destun 50WP) on rat hepatic microsomal enzymes, aniline hydroxylase and amino-pyrine N-demethylase.

Investigations have been carried out to determine the effects of the herbicide 1.1.1 trifluoro-N-(2-methyl-4-phenyl sulfonyl) methane sulfonamide (Destun) on some hepatic microsomal drug metabolizing enzymes in rat. Administration of 100 mg herbicide/kg rat (i.p. or oral) resulted in a stimulation of aniline hydroxylase and p-aminopyrene N-demethylase activities by 1.3 fold and 1.6 fold respectively. A dose-related increase in enzyme activities was observed with a maximum effect at about 100 mg Destun/kg rat. The increased microsomal protein content, liver weight: body weight ratio and decreased sleeping time in the herbicide-treated animals indicated the possibility of Destun being an "inducer". Results of investigations on the kinetic properties of aniline hydroxylase and p-aminopyrene-N-demethylase on administration of Destun suggests that in addition to its inducer effect, the herbicide could stimulate the enzyme activities by decreasing the affinity of these enzymes for their respective substrates.