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Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl<sub>4</sub>-Induced Hepatotoxicity in ICR Mice

Go, Jun, Kim, Ji Eun, Koh, Eun Kyoung, Song, Sung Hwa, Sung, Ji Eun, Lee, Hyun Ah, Lee, Young Hee, Lim, Yong, Hong, Jin Tae, Hwang, Dae Youn
Nutrients 2016 v.8 no.3
alanine transaminase, alkaline phosphatase, antioxidants, aspartate transaminase, blood serum, carbon tetrachloride, caspase-3, cell death, collagen, hepatotoxicity, histopathology, interleukin-10, interleukin-6, lactate dehydrogenase, liver cirrhosis, malondialdehyde, mice, mitogen-activated protein kinase, phosphorylation, protective effect, secretion, signal transduction, superoxide dismutase, transforming growth factor beta 1, tumor necrosis factor-alpha
To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl<inf>4</inf>)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl<inf>4</inf> injection. The GEGR/CCl<inf>4</inf> treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl<inf>4</inf> treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl<inf>4</inf> treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl<inf>4</inf> treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-β1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl<inf>4</inf> treatment through upregulation of the anti-inflammatory and antioxidant system.