Comparative Uptake of Quinine into Sections of Mouse Brain

Abstract

A quinine rectal formulation will be useful in pre-referral in primary health facilities, in homes and rural areas where health facilities are not located. It will also be life-saving in hospitals in cases of circulatory collapse in severe malaria. Cerebral malaria (CM) affects some specific regions of the brain focusing on local events around the cerebral microvasculature. Quinine and quinidine have been reported to block the neuronal connexin 36, the major receptor for parasite sequestration in the microvasculature of infected subjects. A new formulation of quinine suppository to be used in early initiation of treatment of CM was tested on the murine mice model which mimics the human CM. The model was used to assess the uptake of quinine from the suppository into the various sections of the mouse brain and compare uptake between the parasitized and the non-parasitized brain sections. Quinine uptake was quantified using the high pressure liquid chromatography. Uptake of quinine from this suppository formulation was confirmed in the four sections of the brain of the two groups of mice within 30 min. ANOVA and paired t-test revealed a non-significant difference in uptake between the parasitized and non-parasitized animals {F(1,46)=0.42, p -value=0.52>0.05}. F-test to check equality of variance, {F=3.60, p- value=0.003 <0.05} was however statistically significant at the 0.05 level and it can be concluded that the expected difference between the two groups exists. The medulla oblongata had the highest uptake at 30min while the olfactory lobe consistently had the highest concentration of quinine thereafter (60min-240 min) and cerebrum had the lowest quinine uptake. Presence of parasites does not seem to affect uptake into the brain, it however seems to affect the disposition of the absorbed quinine in parasitized animals. Time has a significant effect on quinine uptake in the brain sections of the two groups. Uptake amongst the four brain sections in the parasitized animals is statistically different and appears to be biphasic.