TY - JOUR
T1 - Ethanol extracts collected from the Styela clava tunic alleviate hepatic injury induced by carbon tetrachloride (CCl4) through inhibition of hepatic apoptosis, inflammation, and fibrosis
AU - Koh, Eun Kyoung
AU - Kim, Ji Eun
AU - Song, Sung Hwa
AU - Sung, Ji Eun
AU - Lee, Hyun Ah
AU - Kim, Kil Soo
AU - Hong, Jin Tae
AU - Hwang, Dae Youn
N1 - Publisher Copyright:
© 2017 The Japanese Society of Toxicologic Pathology.
PY - 2017
Y1 - 2017
N2 - The Styela clava tunic (SCT) is known as a good raw material for preparing anti-inflammatory compounds, wound healing films, guided bone regeneration, and food additives. To investigate whether ethanol extracts of the SCT (EtSCT) could protect against hepatic injury induced by carbon tetrachloride (CCl4) in ICR mice, alterations in serum biochemical indicators, histopathology, hepatic apoptosis, inflammation, and fibrosis were observed in ICR mice pretreated with EtSCT for 5 days before CCl4 injection. EtSCT contained 15.6 mg/g of flavonoid and 37.5 mg/g phenolic contents with high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (93.3%) and metal chelation activity (46.5%). The EtSCT+CCl4-treated groups showed decreased levels of ALT, LDH, and AST, indicating toxicity and a necrotic area in the liver, while the level of ALP remained constant. The formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the EtSCT+CCl4-treated groups. Furthermore, the levels of pro- and anti-inflammatory cytokines and the phosphorylation of p38 in the TNF-α downstream signaling pathway rapidly recovered in the EtSCT+CCl4-treated groups. The EtSCT+CCl4-treated groups showed a significant decrease in hepatic fibrosis markers including collagen accumulation, MMP-2 expression, TGF-β1 concentration, and phosphorylation of Smad2/3. Moreover, a significant decline in malondialdehyde (MDA) concentration and enhancement of superoxide dismutase (SOD) expression were observed in the EtSCT+CCl4-treated groups. Taken together, these results indicate that EtSCT can protect against hepatic injury induced by CCl4- derived reactive intermediates through the suppression of hepatic apoptosis, inflammation, and fibrosis.
AB - The Styela clava tunic (SCT) is known as a good raw material for preparing anti-inflammatory compounds, wound healing films, guided bone regeneration, and food additives. To investigate whether ethanol extracts of the SCT (EtSCT) could protect against hepatic injury induced by carbon tetrachloride (CCl4) in ICR mice, alterations in serum biochemical indicators, histopathology, hepatic apoptosis, inflammation, and fibrosis were observed in ICR mice pretreated with EtSCT for 5 days before CCl4 injection. EtSCT contained 15.6 mg/g of flavonoid and 37.5 mg/g phenolic contents with high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (93.3%) and metal chelation activity (46.5%). The EtSCT+CCl4-treated groups showed decreased levels of ALT, LDH, and AST, indicating toxicity and a necrotic area in the liver, while the level of ALP remained constant. The formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the EtSCT+CCl4-treated groups. Furthermore, the levels of pro- and anti-inflammatory cytokines and the phosphorylation of p38 in the TNF-α downstream signaling pathway rapidly recovered in the EtSCT+CCl4-treated groups. The EtSCT+CCl4-treated groups showed a significant decrease in hepatic fibrosis markers including collagen accumulation, MMP-2 expression, TGF-β1 concentration, and phosphorylation of Smad2/3. Moreover, a significant decline in malondialdehyde (MDA) concentration and enhancement of superoxide dismutase (SOD) expression were observed in the EtSCT+CCl4-treated groups. Taken together, these results indicate that EtSCT can protect against hepatic injury induced by CCl4- derived reactive intermediates through the suppression of hepatic apoptosis, inflammation, and fibrosis.
KW - Apoptosis
KW - Fibrosis
KW - Hepatic injury
KW - Inflammation
KW - Styela clava tunic
KW - Superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=85032191976&partnerID=8YFLogxK
U2 - 10.1293/tox.2017-0021
DO - 10.1293/tox.2017-0021
M3 - Article
AN - SCOPUS:85032191976
SN - 0914-9198
VL - 30
SP - 291
EP - 306
JO - Journal of Toxicologic Pathology
JF - Journal of Toxicologic Pathology
IS - 4
ER -