ABSTRACT
<p><b>OBJECTIVE</b>To study the immunotoxicity induced by 9,10-dimethyl-1,2-benzathrancene (DMBA) in metallothionein gene-knocked-out mice [MT(-/-)] as compared with that in wild-type mice [(MT(+/+)].</p><p><b>METHODS</b>Female mice were treated with 25 mg/kg and 50 mg/kg of DMBA i.p., respectively and immunized with sheep red blood cells (SRBC) i.v. on the following day and rechallenged by injection of SRBC via footpad s.c. on the fourth day post-immunization. Humoral and cell-mediated immune function was assessed by the number of spleen IgM antibody plaque formation cells (PFC) to SRBC and cell-mediated delayed-type hypersensitivity (DTH) measured by footpad swelling thickness.</p><p><b>RESULTS</b>After treatment with 25 mg/kg DMBA, a decrease in weight of their spleen and thymus and PFC/spleen were observed in MT(-/-) mice, while only decrease in thymus weight of MT(+/+) mice. The humoral function was suppressed by 72% in MT(-/-) mice. No obvious change in cell-mediated immune function was observed both in MT(-/-) and MT(+/+) mice. Both humoral and cell-mediated immune function were suppressed more severe (91%) in MT(-/-) mice treated with 50 mg/kg DMBA than those treated with 25 mg/kg DMBA (72%). DTH was not altered by DMBA in MT(+/+) mice. The weight of their spleen and thymus decreased and humoral immune function suppressed in MT(+/+) mice, but these changes were significantly less severe. No obvious suppression of cell-mediated immune function was observed in MT(+/+) mice.</p><p><b>CONCLUSION</b>Their humoral and cell-mediated immune function was more susceptible to being suppressed by DMBA in MT(-/-) mice, indicating that MT could protect their immune function from damage caused by DMBA.</p>
Subject(s)
Animals , Mice , 9,10-Dimethyl-1,2-benzanthracene , Toxicity , Immunity , Metallothionein , Physiology , Mice, Inbred C57BL , Mice, Knockout , Organ SizeABSTRACT
Objective To investigate the hepatoprotective effect of Propolis alcohol-extract (PAE) against acetaminophen (APAP)-induced acute hepatic damage in mice and to explore the possible mechanism.Methods Sixty-three C57BL/6 MT(-/-)mice were equally randomized into 9 groups.The normal control group and the model group received gastric gavage of normal saline (20 mL?kg-1),four PAE groups were given PAE in the dose of 12.5,25,50 and 100 mg?kg-1 respectively,alcohol +APAP group and alcohol control group received 20 %alcohol 20 mL?kg-1 and PAE control group was given PAE in the dose of 100 mg?kg-1 qd,for 4 consective days.Thirty miniutes after last administration,the mice in the normal control group,PAE control group and alcohol control group received saline 10 mL?kg-1,and the mice in other groups received APAP 380 mg?kg-1 to induce acute hepatic injury.The activities of serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined,and the liver tissues were collected for histopathological assessment by HE staining under light microscope.The ratio of glutathione (GSH) and oxidized glutathione (GSSG),and the content of GSH,GSSG and malondialdehyde (MDA) in liver homogenate were also measured.Results Compared with the model group,PAE could markedly decrease serum ALT,AST and LDH activity,reduce the MDA level in liver homogenate,and increase hepatic GSH content and the ratio of GSH/GSSG in the liver homogenate.The hepatic histopathological changes in liver were also significantly ameliorated.In PAE control group,GSH content and the ratio of GSH/GSSG were also increased.However,the above indexes remained unchanged in alcohol control group.Conclusion The propolis alcohol-extract can prevent the liver from PAP-induced acute hepatic injury.