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.

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.