Evaluating plasmodium berghei infection influence and asiaticacid administration efficacy in sprague dawley male rats: effects on parasitamia, glucose homeostasis and renal electrolyte handling.
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Date
2016
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Abstract
Introduction: Five human-infecting Plasmodium species orchestrate varied pathophysiology
culminating in malaria. Despite being treatable, malaria has high mortality and morbidity in
pregnant women and children under five years. Current treatment is hampered by drug resistance,
toxicity and failure to address malaria induced pathology directly. Asiatic acid has antioxidant,
pro-oxidant, antihyperglycaemiac renoprotective qualities which may be anti-disease properties
in malaria. Very little is currently known or reported about these asiatic acid anti-disease
perspectives in malaria and therefore require further investigations. The aim of this study was to
investigate the influence of asiatic acid administration and malaria infection on parasitaemia
suppression, glucose homeostasis, renal function and electrolyte handling in Plasmodium
berghei-infected Sprague Dawley male rats.
Methods: Three sub-chronic studies and one acute study were conducted. The sub-chronic
protocol involved per-oral pre- and post-infection administration of asiatic acid (5, 10, 20 mg/kg)
and post-infection transdermal drug delivery system application of asiatic acid (5, 10, 20 mg/kgamidated
hydrogel matrix pectin patch). Acute studies included post-infection oral glucose
tolerance response to asiatic acid. Influence of asiatic acid on %parasitaemia changes,
physicochemical changes, immunological effects of malaria, haematological results of malaria,
antioxidant capacity, glucose homeostasis, renal function and renal electrolyte handling were
investigated.
Results: Asiatic acid suppressed parasitaemia to varying extents with asiatic acid 10mg/kg and
5mg/kg emerging as the most efficacious amongst the three doses by per oral administration and
transdermal delivery drug delivery system, respectively. Malaria suppression occurred in both
pre-infection and post-infection administration of asiatic acid. Asiatic acid preserved
physicochemical parameters, ameliorated haematological effects of malaria, influenced
immunological effects of malaria, modulated glucose homeostasis in malaria, protected renal
function and electrolyte handling in malaria. Asiatic acid improved glucose tolerance response in
acute malarial states. Antioxidant status was also improved in malaria.
Conclusions: Asiatic acid displayed chemoprophylactic and chemotherapeutic effects in malaria.
Asiatic acid has both glucose homeostatic and renoprotective properties in malaria. The
antioxidant characteristics of the amphiphilic asiatic acid seem to exert anti-disease and antiparasitic
effects in malaria. Asiatic acid may be used as an antimalarial compound with ability to
ameliorate malaria associated pathophysiology.
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Doctoral Degree. University of KwaZulu-Natal, Durban