Mitochondrial ubiquinol-cytochrome C reductase a chemotherapeutic target in human malarial parasite

Orcrl Sessions I Purasitology

242

INDICATION

OF

O-0457

BENZIMIDASOLE

RESISTANCE IN SHEEP, CATTLE IN NORTH-WEST PART POLAND Ram&

International 47 (Suppl.) (1998) 133-281

AND PIGS

A., Balicka-Ramisz A.

CHANGES IN SHEEP IN INVITRO STUDIES

INDUCED

NODULAR

WORM

Kumar Dinesh* and Lal S.S. Deptt. of Zoology, C.C.S. University,

Department of Animal Hygiene and Prophylaxis, University of Agriculture, Dr Judyma St. 6,72-466

MEBENDAZOLE

Szczecin, Poland

Oesophagostomm

The authehnintic resistance of mematodes in sheep, cattle and sows was investigated on 3 farms in North-West part Poland in 1997. On all farms a questionnaire was filled in with relevant data for the survey, such as anthelmintic usage during the last years, grasing management in sheep and cattle, way of pig feeding etc. The farms were visited thrice - before and twice 7 and 14 days after treatment. During the first visit, groups of 15 animals were formed. All animals were weighed before treatment and from each animal faecal samples were individually taken. One group in each farm remained untreated as a control. Benzimidazoe - fenbezan (fenbendazol) was administered in following doses- sheep, pigs - Smg/kg body weight, cattle-7,5 m@g body weight The drug resistance was ascertained by the faecal eggcount depression test (FECDT). Results. Based on the FECRT, benzimidazole gastrointestinal nematodes resistance animals were demonstrated in all farms In sheep the efficacy of tretment ranged from 30,9 to l9,7 per cent, in cattle from 40 to 16.6 percent and in sows against Oesophagoronimum sp from 50 to 25 5 per cent respectively 7 and 14 days aRer treatment

Meerut-

250 005 INDIA

is commonly

colwmbianum

in sheep and sometimes in man. Prevalances high and morbidity 1995).

is significant

found

of infection are

(Polderman

and Blotkamp

In present studies low and high dose 10 pg/ml and

50 pgiml concentration

of Mebendazole

treatment

was given

in invitro method to the parasite. Light and scanning electron microscopic

studies were done after 6, 8, and I2 hours. Light

microscopy

showed that the body wall and intestine

were

severely affected part by the action ofan anthelmentic showed degeneration vaculation

in the hypodermis,

at both concentrations

were observed in hypodermos.

Worm

disorganisation

(10 rgiml

Electron

and

and 50 pg/ml)

microscope

studies

have shown that the cuticle was affected at high concentration 50 &ml

of Mebendazole showing shrinkage, wrinkles, folding,

rupturing and evaginations

Mebendazole was able to penetrate

into the cuticle of Oesophugostomum

columbranttm

shrinkage and evagination or folding at 50 &ml Slight alteration at 10 pgiml

rupturing

causing

concentration,

and folding were also observed

The present studies revealed that mebendazole

is more toxic for Oesophagostomm

cohttbtanmt.

Mebandazole

induced more severe changes in the cuticle, hypodermis. somatic muscles, intestine and all absorptive The toxicity

and harmfullness

surfaces of the parasite.

should be taken seriously by

the anthelmintic leading pharmaceuticals The knowledge derived from above

studies would

O-0458

0-0156

MITOCHONDRIAL

be helpful

WIOUINOL-CYTOCHROME

CHEMOTHERAPEUTIC

THE FIRST OCCURRENCE OF ANTHELMINTIC RESISTANCE IN STRONGYLID NEMATODES SHEEP AND HORSES IN CZECH REPUBLIC

OF Kiunokrai.,

Chroust K

Rama

The etficacg of levamisole. mebendazole. ivermectm and

may enzyme

gastrointestinal fenbenda/ole

ncmdlodc~

to le\ ainiwle the etficac!

(5 meI#’ I \rith

(7 5 1113 kc.‘)awi values c,? 67 XoO and

10330,

of the

malarIaI

for antlmalanal

sites

of the

had llnle

7~lc/tr,\/,,r,/r~1,///\ spp Considcrnhle rt’Gstance t0 niebend;irolr (8 mg Lg.‘) and ltnbendarole (7 5 my bs ‘). ~.lth the rrrpr‘crl\c FECR’I value3 of61 5”” and X_( IOU. !!a> tbund 111equine vn.111 stronyyles The rwslancc iu hen71m1da/~~l~s \tas wntirnwd I>\

have

llnle

reductase

drug

lnhlbltory was

more

design

was

markedly

effect senswe

In human

was

found

Our

and also the

resuts drug

would

Unlverslty.

lower

enzyme.

growth

to InhibitIon

provide

parasite,

catalytic

m.

enzyme

of

efflclency

the mouse qulnone

were

lnterestlng,tne drug, than

potential

the

liver

bIndIng

and myxothlazole.whlch

by antImalarial

therapeutic

system

mltochondrla

different

antimycln

the malarial

from

that from

affecting

on P.falclDarum against

than

transport

malarial

that

chlorophenyl)cyclohexyll-3-hydroxy-1,4-naphthoqu~none, enzyme

P

electron

purified

lnhlbltors

reductase acwties

A

PARASITE

Chulalongkorn

was

L[UILtlP.lt

ClassIcal

mammalian

antlmalarlal

Prapunwattana,

the mitochondrlal

c reductase

reductase enzyme

N,

MALARIAL

ThaIland

cultivated

mitochondrial

C REDUCTASE

IIN HUMAN

Suraveratum.

that

ublquinol-cytochrome

Plasmodlum

TARGET

Facultyof Medicine,

to demonstrate

be a target

83 7’b. respecllvel! The Infecttous lar\ar: obtained ti.onl c’g!psot resistant slrains \berc identitied as (hwrkrg/frspp and

the HiA as well The rehi\lancc \~as non Iiwnd it1 CAIIC I‘hr above-tllerltiolled tinding\ cc)ntirnl the ncccs~~r~ ot‘<)thel btudies ofanthelmitil~c rcsislancc 111donwsrlc anilllills iii the C/cch Republtc

Rd, Bangkok

In order

doramectin was studied in selected farms of sheep. cattle and horses with naturally acquired stronyylid infections To prove the anthelmintic resis1ance He used II) WIYI tiwal eg count reduction test (FE<‘RT) and in the case ~~l‘benzinlidazol~ anthelmintics also 1~ \‘//ro egg haich assa\ (Eli:\) The FECRT results in sheep proved the occurrence ot’resistanr strains of

of Bochemlstry.

IV

Department of Parasitology. Faculty of Veterinary Medicine. University of Veterinary and Pharmaceutical Sciences. Brno. Czech Republic

SR,

Krungkrai.

Department

in drug designing.

found

to

malarIaI

2-[&a&4-(4’the

mammalian

of the enzyme

target