The combined treatment of praziquantel with osteopontin immunoneutralization reduces liver damage in Schistosoma japonicum-infected mice.
The aim of this study was to evaluate the therapeutic effects of osteopontin neutralization treatment on schistosome-induced liver injury in BALB/C mice. We randomly divided 100 BALB/C mice into groups A, B, C, D and group E. Mice in all groups except group A were abdominally infected with schistosomal cercariae to induce a schistosomal hepatopathological model. Mice in group C, D and group E were respectively administered with praziquantel, praziquantel plus colchicine and praziquantel plus neutralizing osteopontin antibody. We extracted mouse liver tissues at 3 and 9 weeks after the 'stool-eggs-positive' day, observed liver histopathological changes by haematoxylin-eosin and Masson trichrome staining and detected the expression of osteopontin, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β1) by immunohistochemistry, RT-PCR and Western blot. We found that praziquantel plus neutralizing osteopontin antibody treatment significantly decreased the granuloma dimension, the percentage of collagen and the expression of osteopontin, α-SMA and TGF-β1 compared to praziquantel plus colchicine treatment in both the acute and chronic stage of schistosomal liver damage (P<0·05). So we believe that the combined regimen of osteopontin immunoneutralization and anti-helminthic treatment can reduce the granulomatous response and liver fibrosis during the schistosomal hepatopathologic course.
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
Bo-Lin
BL
Chen
Gui-Ying
GY
Zhang
Shi-Ping
SP
Wang
Qian
Q
Li
Mei-Hua
MH
Xu
Yue-Ming
YM
Shen
Lu
L
Yan
Huan
H
Gu
Jia
J
Li
Y L
YL
Huang
Yi-Bing
YB
Mu
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D001161:Arteriosclerosis; D004359:Drug Therapy, Combination; D005260:Female; D006099:Granuloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007153:Immunologic Deficiency Syndromes; D008099:Liver / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009404:Nephrotic Syndrome; D010009:Osteochondrodysplasias; D053495:Osteopontin / Q000276:immunology* / Q000378:metabolism; D011223:Praziquantel / Q000494:pharmacology / Q000627:therapeutic use*; D000081207:Primary Immunodeficiency Diseases; D011655:Pulmonary Embolism; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000472:pathogenicity; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016896:Treatment Outcome
D057134:Antibodies, Neutralizing; D053773:Transforming Growth Factor beta1; D053495:Osteopontin; D011223:Praziquantel