title: Association of heme oxygenase 1 with the restoration of liver function after damage in murine malaria by Plasmodium yoelii.
abstract: The liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. However, the molecular events leading to the restoration of liver function after malaria are still obscure. To study this, we developed a suitable model wherein mice infected with Plasmodium yoelii (45% parasitemia) were treated with the antimalarial α/β-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. Liver function tests clearly indicated that complete recovery of liver function occurred after 25 days of parasite clearance. Analyses of proinflammatory gene expression and neutrophil infiltration further indicated that hepatic inflammation, which was induced immediately after parasite clearance from the blood, was gradually reduced. Moreover, the inflammation in the liver after parasite clearance was found to be correlated positively with oxidative stress and hepatocyte apoptosis. We investigated the role of heme oxygenase 1 (HO-1) in the restoration of liver function after malaria because HO-1 normally renders protection against inflammation, oxidative stress, and apoptosis under various pathological conditions. The expression and activity of HO-1 were found to be increased significantly after parasite clearance. We even found that chemical silencing of HO-1 by use of zinc protoporphyrin enhanced inflammation, oxidative stress, hepatocyte apoptosis, and liver injury. In contrast, stimulation of HO-1 by cobalt protoporphyrin alleviated liver inflammation and reduced oxidative stress, hepatocyte apoptosis, and associated tissue injury. Therefore, we propose that selective induction of HO-1 in the liver would be beneficial for the restoration of liver function after parasite clearance.
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Sumanta
authors.initials: S
authors.lastname: Dey
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Somnath
authors.initials: S
authors.lastname: Mazumder
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Asim Azhar
authors.initials: AA
authors.lastname: Siddiqui
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: M Shameel
authors.initials: MS
authors.lastname: Iqbal
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Chinmoy
authors.initials: C
authors.lastname: Banerjee
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Souvik
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Rudranil
authors.initials: R
authors.lastname: De
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Goyal
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Samik
authors.initials: S
authors.lastname: Bindu
authors.affiliation: Department of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India ubandyo_1964@yahoo.com.
authors.forename: Uday
authors.initials: U
authors.lastname: Bandyopadhyay
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000254:growth & development*
chemical_list: D000962:Antimalarials; D051547:Heme Oxygenase-1