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Phenotyping of the glutathione S-transferase M1 polymorphism in Zimbabweans and the effects of chloroquine on blood glutathione S-transferases M1-A
No full textClinica Chimica Acta 265 (1997) 145-155The frequency of the null allele phenotype of glutathione S-transferase (GST) M1 was investigated in 114 Zimbabweans and results for a subset of 63 subjects were compared with
genotyping by PCR. In addition, the effect of the antimalarial chloroquine on blood levels of
GSTMl and GSTA in 19 subjects was studied. Quantification of GSTs was by enzyme linked
immunosorbent assays (ELISA). Thirty percent of the subjects were of the GSTMl null
phenotype. Comparison of results of phenotyping by ELISA and genotyping by PCR showed that
16% of samples were in discordance; unknown mutations in the GSTMl gene in the Zimbabwean
population may explain this observation. Chloroquine decreased levels of blood GSTM1 and
GSTA by 50% or more. In populations treated with chloroquine, these decreases in GST activities
might lead to compromised ability to detoxify xenobiotics, could confound GSTMl phenotyping
and might invalidate use of GSTA as an indicator of liver damage. O 1997 Elsevier Science B.V.
Keywords: Glutathione S-transferases; Phenotype; Black Zimbabweans; ChloroquineThe International Program in Chemical Sciences (lpics) Uppsala University. Sweden and the University of Zimbabwe Research Board
Combined use of phenyl-bonded phase clean-up and HPLC for the determination of aflatoxins
No full textarticle from the tropical science journal 1996;36, pages 197-200Phenyl?bonded phase clean-up and HPLC were used to measure aflatoxins in
groundnuts, peanut butter, beans, cowpeas and maize meant for human consumption. Of
277 samples, 84% were al or bleow the 20 pp.b. limil. Of 100 animal feed samples, 28%
were at or below 5 p.p.b., the proposed limit infeedfor milk-producing animals
A Comparison Of Organochlorine Pesticide Residues In Upper Ncema And Lower Umguza Dams, Zimbabwe.
No full textJournal article from page 26 to 30.This study examined the levels of chlorinated hydrocarbons (organochloride
pesticides) in the ecosystem of Ncema and Umguza dams. Samples of water,
water weeds, mud and fish were collected from each dam. The fish species
collected from the two dams were river sardine (Mesobo/a brevianus), branded
bream (Tilapia sparmanii), African catfish (e/arias gariepinus) and red-breasted
bream (Tilapia rendelli). The samples were analysed for hexachlorocyclohexane,
DDT, and its metabolites, DOE and DOD, aldrin and dieldrin. DDT was detected in
all the samples, its concentration ranging from 1,12 J.l9 per kg in water weeds to
265 J.l9 per kg in mud from Upper Ncema dam. Aldrin was also detected in all the
samples (except for branded bream from Upper Ncema dam), the highest level
__being 223 ~g per kg in_ ~atdln~$'-rom Lower Umguza dam. Traces.of
hexachlorocyclohexane were detected in some of the samples, the highest level
of 20,1 ~g per kg in African catfish from Upper Ncema dam. Dieldrin was detected
only in mud samples from Lower Umguza dam at a concentration of 80,5 ~g per
kg. Overall, this study indicates that Upper Ncema dam has a higher pesticide load
compared to Lower Umguza dam
Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney.
No full textA journal article with illustrationsThe effect of chloroquine (CHQ) administration on antioxidant enzymes in rat liver and kidney was
studied. Male Sprague-Dawley rats were administered 20 mglkg CHQ once a week for 4 weeks (chronic treatment)
or a single dose at 10 or 20 mglkg (acute treatment). Antioxidant enzyme activities were determined in cytosolic
fractions of liver and kidney, whereas reduced glutathione (GSH) and malondialdehyde (MDA) were determined in
tissue samples. Results indicate minimal effects of acute CHQ treatment, whereas chronic treatment with CHQ
differentially affected antioxidant enzymes in the two organs. Superoxide dismutase activity was increased nearly
twofold, while activities of selenium glutathione peroxidase (GPX), catalase, and NAD (P) H: quinone oxidoreductase
were decreased in livers of CHQ-treated rats compared to controls. No significant effects of CHQ on glutathione
reductase, GSH, and MDA levels were seen in the liver. Fewer effects of CHQ were observed in the kidney where
a decrease in GPX activity and an increase in MDA levels was seen. Lowering of antioxidant enzymes activities in
the liver by CHQ could render the organ more susceptible to subsequent oxidative stress; while increased MDA
production after CHQ treatment in the kidney indicate that the organ is being subjected to oxidative stress. This
could have implications for prolonged chloroquine intake.International Programme in the Chemical
Sciences (IPICS), Uppsala University, Sweden, and the University of
Zimbabwe Research Board
Hepatic Cytosolic Glutathione S-Transferases Of Ostrich (Struthio Camelus): Partial Characterization And Interaction With Xenobiotics
No full textThe glutathione S-transferases (GSTs) in affinity purified pools of male and
female ostrich liver were studied. The GSTs were purified from crude liver cytosols
by S-hexylglutathione sepharose affinity chromatography with yields comparable
to those reported for GST from mammalian livers. The K, for both glutathione
(GSH) and 1-chloro-2,4-dinitroSenzenzene (CDNB) were determined and found to be
within the range of values known for mammalian and invertebrate species. 1-
chloro-2,4-dinitrobenzene proved to be the best of nine substrates tested to
measure activity. Activity was inhibited by bromosulphophthalein and cibacron
blue which are well known inhibitors of the mammalian enzyme. Our results
indicate that the ostrich liver enzymes behave similarly to the mammalian liver
enzyme in terms of substrate requirements and inhibition characteristics.Zimbank.
International Program in Chemical Sciences, Uppsala University, Sweden and the Research
Board, University of Zimbabwe
Xenobiotic metabolizing enzymes of the freshwater snails.Planorbella and lymnaea (RADIX)Natalensis.
No full textJournal of medical and applie macologyVery little is known about the ability of snails to metabolise and remove xenobiotics such as molluscicides. The present study was conducted to determine whether the
freshwater snails Planorbella duryi and Lymnaea (Radix) nntaIensis possess two of the
major enzyme systems of detoxication, namely the P450 monooxygenase system and the
glutathione Stransferases. We were able to measure microsomal cytochrome b5 and
NADPH cytochrome c reductase activity, indicating a functional mixed function oxidase
system. However, probing with three known substrates for the mammalian enzyme, we
were unable to detect any cytochrome P450 mediated activity. Glutathione Stransferase
activity was detectable in cytosolic fractions. In general, the activities detectable in snails
were much lower than in mammalian liver preparations. The existence of these enzymes
in snails suggests that studies should be undertaken to observe the interaction between
these enzymes and xenobiotics such as candidate molluscicides.
Key words: Planorbella duyi, Lyrnnaea (Radix) natalensis, cytochrome P450, glutathionelnternational Program in Chemical Science, Uppsala University Sweden and Research Board, University of Zimbabwe
Fault-plane solutions of the Deka Fault zone and mid-zambezi Valley
No full textAn analysis of twenty-one fault-plane solutions from the Deka Fault zone and the
mid-Zambezi Valley shows normal (dip-slip) faulting with a strike-slip component.
The fault planes strike in a south-westerly direction in conformity with the
north-easterly geologically observed striking lineaments. The T axes of the fauIt
planes obtained are nearly horizontal with their domains in the north-west and
south-east quadrants of the focal sphere. One composite focal mechanism solution
for the seismically active area just to the west-north-west of the Kariba dam is
constructed. The overall results are correlated with the known tectonics of the area.
The stress regime obtained in this study is predominantly influenced by a
north-west-south-east tensional stress field that is orthogonal to the orographic
strike direction of the main geological structures
Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats.
No full textAn article with illustrations.The effects of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on the phannac~kinetics of praziquantel (PZQ), a
schistosomicide were studied in Spnrgue-Dawley rats. Blood samples at different time intervals were obtained by severing the tail
vein and were analyzed for unchanged PZQ by HPLC. The PB-pretreated rats showed a &fold decrtase in AUC, a 5-fold decrease in
Cmax and an 8-fold increase in Ch compared to the saline treated controls. The MC-pretreated rats and their oliveoil treated
controls did not show any statistically significant diffmnces in the above parameters. These results suggest that PZQ is extensively
metabolised by PB-inducible cytochrome P-450 isoforms and not by MC-inducible isoforms. These findings also suggest that the
bioavailability of praziquantel could be altered to a significant extent in humans taking drugs that are phenobarbital type inducers.Research Board of the University of Zimbabwe and the International
Programme in the Chemical Sciences, Sweden
The effect of schistosomiasis on the covalent binding of 2-acetylaminofluorene to mouse liver macromolecules in vivo and in vitro
No full text1. Sprague DH, Yang JC and Ngai SH, Effects of isoflurane and halothane on contractility and the cyclic 3', 5'-adenosine monophosphate system in the rat aorta. Anesthesiology 40: 162-170, 1974. 2. Aronstam RS, Anthony BL and Dennison RL Jr, Halothane effects on muscarinic acetylcholine receptor binding in rat brain. Biochem Pharmaco135: 667-672, 1986.The covalent binding of [14C]acetylaminofluorene (AAF) to macromolecules in vivo and in vitro was measured in Schistosoma mansoni-infected and in non-infected mice. Liver microsomes from infected mice demonstrated a 42% decreased capacity to mediate covalent binding of AAF to DNA. In addition, the extent of binding of AAF to liver macromolecules in vivo was generally less in infected than non-infected mice.Research Support, Non-U.S. Gov't, In Vitr
The Effect Of Three Species Of Schistosomes On Hepatic Drug Metabolism In Male BALB/ Mice
No full textAn article published in the European Journal of Pharmacology.Schistosomiasis is a parasitic disease that affects over 200 million people in the world. S.mansoni and S.haematobium are of medical importance while S.mattheei is primarily of veterinary concern. It is important to know the effect that the disease has on elimination of xenobiotics. The effect of S.mansoni infection on thiopental sleeping times and zoxazolamine paralysis times has previously been reported by other workers as well as by us. Similar work on S.mattheei and S.haematobium infected animals, however, has not been reported in the literature. The effect of S.mattheei and S.haematobium on thiopental sleeping times was therefore studied and compared to results obtained for animals infected with S.mansoni. Thiopental sleeping times and egg loads of infected animals are shown in Table 1. Although S.haematobium infected animals did not have detectable levels of parasite eggs in their livers at 8 weeks post-infection, significant numbers of eggs were detectable at 12 weeks post-infection. This is in agreement with the observed delayed maturation of S.haematobium schistosomulae in rodents as compared to S.mansoni or S.mattheei. The number of worm pairs in each group was as follows: S.mattheei 20-25, S.mansoni 8-10, and S.haematobium (both 8 and 12 weeks post infection)
3-10 pairs. The sleeping times of all infected animals were prolonged when compared to their respective controls. The reasons for this are not clear but it is likely that the parasite egg-induced granulomas as well as the physical obstruction to portal blood flow caused by migration of?worms from mesenteric to portal veins play a significant role. Data obtained in this laboratory on drug metabolism in vitro in S.mansoni infected animals indicate that the activity of hepatic drug metabolising enzymes is also altered, but generlllly only in animals that have developed parasite egg-induced granulomas in their livers