Comparison of the effects of oral and transdermal adminstration of chloroquine on selected haematological parameters and inflammatory cytokines in P.berghei- infected male Sprague-Dawley rats.
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Date
2016
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Abstract
Introduction
Chloroquine (CHQ), the mainstay antimalarial drug accumulates in organs and alters physiological
function. Hypoglycaemia, impairment of kidney function and anaemia are among an array of
pathophysiological manifestations caused by malaria infection or oral CHQ treatment. However, it is
unclear whether this anaemia is solely due to the parasite or by CHQ. Therefore, there is need to
investigate and distinguish between the pathophysiological effects of malaria alone and those of CHQ
treatment. The purpose of the current study was to investigate and compare the effects of using oral
CHQ treatment or a transdermal CHQ patch in the treatment of malarial infection. To this effect, we
evaluated changes in haematological parameters as well as plasma cytokine concentrations in male
Sprague-Dawley rats. We also looked at the morphological effects of various visceral organs
following malarial infection and subsequent treatment with CHQ. The study duration was 3 weeks
divided into pre-treatment (days 0-7), treatment (8-12) and post treatment (13-21) periods. CHQ
treatment was either administrated orally (30mg/kg, twice daily) or via a once off CHQ matrix patch
(56mg/kg). Oral CHQ treatment reduced red blood cell count, haematocrit, haemoglobin and mean
corpuscular haemoglobin in non-infected and infected animals. Topical application increased the
above parameters in infected rats. Oral CHQ decreased pro-inflammatory cytokine concentration in
infected rats on the day (day 8 of the experiment) of the treatment period in comparison to pretreatment
(baseline) measurements. However, on the last day (day 12) of the treatment period and
during the post-treatment period there was an increase in pro-inflammatory cytokine concentration
while patch application decreased pro-inflammatory cytokine concentration in infected rats
throughout the experimental period. P.berghei-infected rats following oral and transdermal CHQ
delivery showed mild morphological changes on the liver, heart, kidney and spleen by comparison to
infected control animals. In non-infected rats oral CHQ treatment showed adverse morphological
effects on the architecture of these organs, while no changes were observed following transdermal
CHQ delivery. C-reactive protein is an acute phase protein, a component of innate immune response
and is useful in early detection of inflammation. Oral CHQ administration increased CRP
concentration. However, CRP concentration was not affected in patch treated animals. The results of
the current study have demonstrated that the once off patch application of the CHQ-formulation has
no morphological effects when compared to oral administration of CHQ on various organs. The
ability of the pectin-CHQ matrix patch to provide slow, sustained CHQ releases into the circulation,
avoids drug dumping in various tissue organs therefore circumventing the adverse effects associated
with oral administration of CHQ. In addition, our results show that both CHQ and malaria parasite
result in the development of anaemia by affecting RBCs and plasma pro-inflammatory cytokines.
These findings suggest that transdermal CHQ delivery could therefore be used in conjunction with or
as an alternative treatment in the management of malaria.
Description
Master’s Degree. University of KwaZulu-Natal, Durban.