title: Immunomodulatory effect of diethylcarbamazine citrate plus filarial excretory-secretory product on rat hepatocarcinogenesis.
abstract: Diethylcarbamazine citrate (DEC) had a significance in anti-filarial chemotherapy, while excretory-secretory product (ES) is released from adult filarial females. The target of the current study was to examine the immunomodulatory effect of DEC, Setaria equina ES or a combination of them on rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN). In vitro effect of combined DEC and ES or ES alone on lipopolysaccharide (LPS)-stimulated rat peripheral blood mononuclear cells (PBMCs) was tested through IFN-γ assay in culture supernatants. In addition, single or repeated doses of DEC, ES or DEC+ES have been applied in white albino rats to test the effect on HCC. Levels of IFN-γ and anti-ES IgG antibodies in rat serum were assayed using ELISA. Hemolytic complement activity (CH50) was determined in serum while the concentration of nitric oxide (NO) was assayed in liver tissue. The infiltration of NK cells as well as the expression of MHC Iproliferating cell nuclear antigen (PCNA), inducible NO synthase (iNOS), Bcl2 and p53 were determined using immunohistochemistry. There was a dose-dependent increase in IFN-γ after in vitro exposure to DEC+ES. Repeated ES doses increased NO concentration (p<0.05) and expression of iNOS but reduced CH50 (p<0.001), while repeated DEC+ES doses could increase anti-ES IgG (p<0.01), IFN-γ level (p<0.05) and NK cell infiltration. The same treatments could also reduce the expression of MHC I expression, PCNA, Bcl2 and p53. This study has shown immunomodulatory and protective effects of DEC+ES repeated doses on rat HCC.
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt. Electronic address: mahmoud_1232000@yahoo.com.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdel-Latif
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt.
authors.forename: Thabet
authors.initials: T
authors.lastname: Sakran
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: El-Shahawi
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt.
authors.forename: Hoda
authors.initials: H
authors.lastname: El-Fayoumi
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt.
authors.forename: Al-Mahy
authors.initials: AM
authors.lastname: El-Mallah
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy*; D002478:Cells, Cultured; D004049:Diethylcarbamazine / Q000008:administration & dosage*; D004052:Diethylnitrosamine / Q000008:administration & dosage; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017182:Setaria Nematode / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D007074:Immunoglobulin G; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D004052:Diethylnitrosamine; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D004049:Diethylcarbamazine
keywords: Diethylcarbamazine citrate; Excretory–secretory product; Hepatocarcinogenesis; Immunomodulation; Rat