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ASIATIC ACID INFLUENCES GLUCOSE HOMEOSTASIS IN P. BERGHEI MURINE MALARIA INFECTED SPRAGUE-DAWLEY RATS.

ABSTRACT: Glucose homeostasis derangement is a common pathophysiology of malaria whose aetiology is still controversial. The Plasmodium parasite, immunological and inflammatory responses, as well as chemotherapeutics currently used cause hypoglycaemia in malaria. Anti-parasitic and anti-disease drugs are required to combat malaria while ameliorating the pathophysiology of the infection. Asiatic acid has anti-hyperglycaemic, antioxidant, pro-oxidant properties useful in glucose homeostasis but its influence in malaria is yet to be reported. Here we present findings on the influence of asiatic acid on glucose metabolism in vivo using P. berghei-infected Sprague Dawley rats.Acute as well as sub-chronic studies were carried out in vivo where physicochemical properties and glucose homeostasis were monitored after administration of asiatic acid (10mg/kg) in both non-infected and infected animals. Glucose metabolism associated biochemical changes in malaria were also investigated.In acute studies, asiatic acid improved oral glucose response while in the sub-chronic state it maintained food and water intake and suppressed parasitaemia. Normoglycaemic control was maintained in infected animals through insulin suppression and increasing glucagon secretion, in both acute and chronic studies. Asiatic acid administration curtailed lactate concentration towards normal.Per oral post-infection asiatic acid administration preserved drinking and eating habits, inhibited sickness behaviour while suppressing parasitaemia. Reciprocal relationship between insulin and glucagon concentrations was maintained influencing glucose homeostasis positively and inhibition of hyperlactaemia in malaria. Abbreviations: ip -intraperitoneal, po -per oral, ig -intragastric, AA-Asciatic acid, OGTT-oral glucose tolerance test, OS-oxidative stress, ROS-reactive oxygen species, NO-nitric oxide, ONOO- - peroxynitrite, BRU-Biomedical Research Unit, SD-Sprague Dawley.

SUBMITTER: Alfred MG

PROVIDER: S-EPMC5416651 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:Background Plasmodium falciparum and tissue dwelling helminth parasites are endemic in sub-Saharan Africa (SSA). The geographical overlap in co-infection is a common phenomenon. However, there is continued paucity of information on how the co-infection influence the blood glucose and insulin profiles in the infected host. Animal models are ideal to elucidate effects of co-infection on disease outcomes and hence, blood glucose, insulin and glycogen profiles were assessed in Sprague-Dawley rats co-infected with P. berghei ANKA (Pb) and Trichinella zimbabwensis (Tz), a tissue-dwelling nematode. Methods One-hundred-and-sixty-eight male Sprague-Dawley rats (weight range 90–150 g) were randomly divided into four separate experimental groups: Control (n = 42), Pb-infected (n = 42), Tz-infected (n = 42) and Pb- + Tz-infected group (n = 42). Measurement of Pb parasitaemia was done daily throughout the experimental study period for the Pb and the Pb + Tz group. Blood glucose was recorded every third day in all experimental groups throughout the experimental study period. Liver and skeletal muscle samples were harvested, snap frozen for determination of glycogen concentration. Results Results showed that Tz mono-infection and Tz + Pb co-infection did not have blood glucose lowering effect in the host as expected. This points to other possible mechanisms through which tissue-dwelling parasites up-regulate the glucose store without decreasing the blood glucose concentration as exhibited by the absence of hypoglycaemia in Tz + Pb co-infection group. Hypoinsulinemia and an increase in liver glycogen content was observed in Tz mono-infection and Tz + Pb co-infection groups of which the triggering mechanism remains unclear. Conclusions To get more insights into how glucose, insulin and glycogen profiles are affected during plasmodium-helminths co-infections, further studies are recommended where other tissue-dwelling helminths such as Taenia taeniformis which has strobilocercus as the metacestode in the liver to mimic infections such as hydatid disease in humans are used.

Project description:BackgroundAnisakiasis is an emerging public health problem, caused by Anisakis spp. nematode larvae. Anisakiasis presents as variable and unspecific gastrointestinal and/or allergic clinical symptoms, which accounts for the high rate of misdiagnosed cases.Methodology/principal findingsThe aim of this study was to characterize the early cellular (6-72 h p.i.) and molecular (6 h p.i.) immune response and general underlying regulatory mechanism in Anisakis infected rats. Each Sprague-Dawley rat was infected with 10 Anisakis spp. larvae by gastric intubation. Tissues with visible lesions were processed for: i) classic histopathology (HE), immunofluorescence (CD3, iNOS, S100A8/A9), and transmission electron microscopy (TEM); ii) target genes (Il1b, Il6, Il18, Ccl3, Icam1, Mmp9) and microRNA (Rat Immunopathology MIRN-104ZF plate, Quiagen) expression analysis; and iii) global DNA methylation. Histopathology revealed that Anisakis larval migration caused moderate to extensive hemorrhages in submucosal and epimysial/perimysial connective tissue. In stomach and muscle, moderate to abundant mixed inflammatory infiltrate was present, dominated by neutrophils and macrophages, while only mild infiltration was seen in intestine. Lesions were characterized by the presence of CD3+, iNOS+, and S100A8/A9+ cells. The greatest number of iNOS+ and S100A8/A9+ cells was seen in muscle. Il6, Il1b, and Ccl3 showed particularly strong expression in stomach and visceral adipose tissues, but the order of expression differed between tissues. In total, three miRNAs were differentially expressed, two in stomach (miRNA-451 and miRNA-223) and two in intestine (miRNA-451 and miRNA-672). No changes in global DNA methylation were observed in infected tissues relative to controls.Conclusions/significanceAnisakis infection induces strong immune responses in infected rats with marked induction of specific proinflammatory cytokines and miRNA expression. Deciphering the functional role of these cytokines and miRNAs will help in understanding the anisakiasis pathology and controversies surrounding Anisakis infection in humans.

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ASIATIC ACID INFLUENCES GLUCOSE HOMEOSTASIS IN P. BERGHEI MURINE MALARIA INFECTED SPRAGUE-DAWLEY RATS.

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