African Journal of Biomedical Research, Vol. 4, No. 3, Sept, 2001, pp. 159-160
Short communication
EFFECT OF CHRONIC
ADMINISTRATION OF INDOMETHACIN ON HAEMATOLOGICAL PARAMETERS IN RATS
ADEDAPO A.A*
AND AIYELOTAN O.
Department of Veterinary Physiology and Pharmacology, University of Ibadan.
Ibadan, Nigeria
*Author for correspondence
Received: July 1999
Accepted in final form: May 2001
Code Number: md01073
Chronic treatment with indomethacin (250mg/kg and 500mg/kg
decreased packed cell volume (PCV) haemoglobin (Hb), Red Blood Cell Count
(RBC) and neutrophil
values but increased the lymphocyte counts.
Keywords: Indomethacin, blood, rat
INTRODUCTION
Indomethacin is a non-steriodal anti-inflammatory
drug that was synthesized in 1963 for the treatment of rheumatoid arthritis.
It is an indolemathylate derivative that has anti-inflammatory, analgesic and
anti-pyretic activities (Gilman et al 1985). It contain not less than 98.5%
and not more that the equivalent of 100.5% of (1-(14-chlorobenzoyl)5-methoxy-indol-3-yl)
acetic acid, calculated with reference to the dried substance (British
Pharmacopoeia, 1998).
Indomethacin exert is effect by potently inhibiting postaglandin
synthesis (Libber et al, (1986). It is used in patient that are refractory to
other drugs. But despite it potency, indometacin is not continually used as an
analgesic or antiphyretic because it s toxic effects have become apparent with
its wider use (Schild, 1980). These adverse effects include gastric and peptic
ulceration which may involve haemorrhage and acute perforation of colonic diverticuli,
nausea, headache, dizziness, depression and psychosis (Gilman et al 1985). Infact
acute renal failure associated with the concomittant administration of indometacin
and triamterene has been reported (Clive and Stoff, 1984).
Indometacin has an intraperitoneal lethal dose of
13mg/kg in rats (Chambers, 988). Infact, this drug has been used widely as a rodenticide
in the local community and the drug is potent in causing death within 1-5 hours
of administration (Makinde, 1991).
In the present
study, the effect of indomethacin haematological parameters are studied in
rats.
MATERIALS
AND METHODS
The Animals
Albino rats of the Wistar
Strain were used for this experiment. The were bought from the Physiology
Department of the University of Ibadan and transferred to the experimental
animals house of the Department of veterinary Physiology and Pharmacology of
the same University. The animals were thus housed under standard laboratory
conditions and had free access to feed and clean water. The animals were fed
on growers mash and stabilized for 2 weeks before the start of the experiment.
Drug
administration
IndocidR was obtained
(strides, Belgium) 25mg capsules with a concentration
of 25mg. Each capsule was emptied carefully into the universal bottle and was
reconstituted using distilled water. The drug was orally administered in doses
of 250mg/kg and 500mg/kg were given to the animal in groups A, and B
respectively. Group C which served as control
Evaluation of Hematological
Parameters
After one-hour administration
through oral route, the blood samples were collected and investigated for
packed cell volume (PCV) using the microhaematocrit method, haemoglobin (HB)
concentration by cyanomethaemoglobin method and red blood cell (RBC) and white
blood cell (WBC) counts by the haemocytometer method.
The values of mean
corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC)
were calculated according to Schalm et al (1975).
The effects of this drug on
the haematological parameters of rats in group A and B were compared with the
control group using student-t-test. Values of P < 0.05 was taken as being
significant.
RESULTS
The results of this study are
as presented in table 1. Treatment of rats with indomethacin at both 250mg/kg
and 500mg/kg doses significantly decreased the PCV (P < 0.05 and P <
0.01), Hb concentration (P < 0.05 and P < 0.01), RBC (P < 0.001) and neutrophil
levels (P < 0.05) when compared with the untreated control (Group C). On
the other hand the total leucocyte count and lymphocyte count of the animals
treated with indomethacin was significantly increased when compared with the
control.
DISCUSSION
There was a marked reduction
in haematological parameters such as PCV, RBC, MCV, MCH and MCHC in the rats
were
administrated 250mg/kg and 500mg/kg doses of the drug. This observation may
be
as a result of the 25mg and 50mg are not doses. Doses are expressed in mg/kg,
e.t.c.
gastro intestinal tract which then lead to the loss of blood causing haemorrhagic
anemia. This has thus precipitated low Hb and RBC count causing low capacity
to carry oxygen with the resultant anoxia cyanosis and respiratory acidosis
which in turn caused the death of the rats within a short period of time (Makinde,
1991). The fact that indometacin is associated with toxic effects in a large
percentage of patients that have been administered with this drug have been established
(Schild, 1980). Infact it was reported that there was a 70-80% reduction by
indometacin of the second pressor response to ethanol. There is thus enhancement
of vasopressin activity by this drug and this can result in water retention (Libber
et al, 1986). This therefore give credence to the acute renal failure associated
with the concomitant use of this drug and triamterene
(Clive and Stoff, 1984).
Table 1- Effect of Indomethacin on Some Haematological
Parameters
Group
|
Dose (mg/kg)
|
PCV (%)
|
Hb g/dl
|
RBC (106)
|
WBC (x103)
|
Neut (%)
|
Lymph
(%)
|
A
|
250
|
32.80 ± 3.56
|
9.00 ± 1.25
|
5.40 ± 0.96
|
10.4 ± 0.48
|
24.00 ± 4.27
|
72.0 ± 5.31
|
B
|
500
|
23.00 ± 1.87
|
6.10 ± 0.5
|
3.30 ± 0.22
|
8.30 ± 0.46
|
24.00 ± 3.54
|
72.0 ± 3.54
|
C
|
Nil
|
38.00 ± 3.7
|
11.7 ± 0.67
|
6.09 ± 0.55
|
4.90 ± 0.68
|
42.00 ± 1.87
|
56.8 ± 1.79
|
Note: PCV=Packed cell Volume; Hb= Haemoglobin;
RBC = Red Blood Cell; WBC = White Blood Cell; Neut = Neutrophil; Lympho =
lymphocyte. *P < 0.05;
**P< 0.01; P< 0.001
The adverse effects of these
may involve haemorrhage and acute perforation of colonic diverticuli, nausea,
dizziness, depression and psychosis (Gilmand, et al, 1985). It is these
adverse effects that actually preclude the routine use of this drug as an
analgesic or antipyretic despite its potency. The 750mg/kg dose of the drug is
surprising not as potent as it should. This may be due to error in drug
administration.
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