title: Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.
abstract: The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/-) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyunseong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Dong June
authors.initials: DJ
authors.lastname: Keum
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jung won
authors.initials: Jw
authors.lastname: Kwak
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hwan-Suck
authors.initials: HS
authors.lastname: Chung
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea; Institute of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001514:Bee Venoms / Q000737:chemistry* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D054467:Phospholipases A2 / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D001514:Bee Venoms; D016207:Cytokines; C556062:IL10 protein, mouse; D020011:Protective Agents; D016753:Interleukin-10; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D054467:Phospholipases A2