Plasmodium-Salmonella Coinfection Induces Intense Inflammatory Response, Oxidative Stress, and Liver Damage: A Mice Model Study for Therapeutic Strategy.
2018
: Impairment of host immune response in malaria favors bacteremia caused by typhoidal or nontyphoidal serovars of Salmonella enterica. Ofloxacin and Artesunate are the drugs that are clinically proven for treating typhoid and malaria, respectively. The study evaluates the host responses upon treatment with antibiotic (Ofloxacin) and antimalarial (Artesunate) in a standardized mice model harboring coinfection. BALB/c mice (18-22 g) were simultaneously coinfected with Plasmodium yoelii nigeriensis (Pyn) and S. enterica serovar Typhimurium (STm) and then treated with Ofloxacin or/and Artesunate from day 4 to day 7. The bacterial burden, liver function enzymes, oxidative stress, m-RNA expression of Toll-like receptors (TLR-2 and TLR-4), Th1/Th2 cytokines, hemeoxygenase-1, and NFкB were assessed. Ofloxacin treatment failed to counter the bacterial proliferation in Pyn-STm coinfected mice. However, upon controlling parasitemia with antimalarial, the efficacy of Ofloxacin could be regained. Elevated bacterial burden with malaria induces the expression of TLR-2 and TLR-4 triggering intense inflammatory response (NFκB, Th1/Th2 cytokines) in coinfected mice. This results in critical liver damage (ALT, AST, and ALP), oxidative stress (lipid peroxidation, total GSH, catalase, and super oxide dismutase), and hemeoxygenase-1 (HO-1). The study concludes that malaria infection aggravates the secondary infection of Salmonella serovars and the control of septicemia is critical in recovery of the coinfected subject.
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