title: Hepatoprotective effect of Arazyme on CCl4-induced acute hepatic injury in SMP30 knock-out mice.
abstract: Arazyme is a novel protease produced by the HY-3 strain of Aranicola proteolyticus, which is a Gram-negative aerobic bacterium that has been isolated from the intestine of the spider Nephila clavata. This study focused on the hepatoprotective effect of Arazyme on carbon tetrachloride (CCl4)-induced acute hepatic injury in senescence marker protein 30 (SMP30) knock-out (KO) mice and SMP30 wild-type (WT) mice. WT mice and SMP30 KO mice were divided into eight groups as follows: (i) two negative control groups (G1, G5) which were treated with a single intraperitoneal (i.p.) olive oil injection. (ii) Two positive control groups (G2, G6) which received a single i.p. CCl4 (0.4mL/kg) injection. (iii) Two vitamin C-treated groups (G3, G7) which received a single oral administration of vitamin C (100mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). (iv) Two Arazyme-treated groups (G4, G8) which received a single oral administration of Arazyme (500mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). Through present study, we could find that Arazyme-treated groups showed decreased degree of liver injury, increased expression of SMP30, decreased expression of phospho-Smad3 (p-Smad3), elevated expression of antioxidant proteins including sorbitol dehydrogenase, dihydropteridine reductase (DHPR), dehydrofolate reductase (DHFR), NADH dehydrogenase, glutathione S-transferase kappa 1 (GSTK1) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) compared with non-Arazyme-treated groups. Therefore, it is concluded that Arazyme plays a significant role in protecting injured hepatocytes by increasing the expression of SMP30, inhibiting the transforming growth factor-beta (TGF-beta)/Smad pathway and elevating the expression of antioxidant proteins.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Da-Hee
authors.initials: DH
authors.lastname: Jeong
authors.forename: Ho-Yong
authors.initials: HY
authors.lastname: Park
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Son
authors.forename: Dong-Ha
authors.initials: DH
authors.lastname: Shin
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Do
authors.forename: Hai-Jie
authors.initials: HJ
authors.lastname: Yang
authors.forename: Dong-Wei
authors.initials: DW
authors.lastname: Yuan
authors.forename: Il-Hwa
authors.initials: IH
authors.lastname: Hong
authors.forename: Moon-Jung
authors.initials: MJ
authors.lastname: Goo
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Ki
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018890:Chemoprevention; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D045726:Metalloproteases / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000378:metabolism; D040901:Proteomics; D012705:Serratia / Q000201:enzymology; D051900:Smad3 Protein / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D010088:Oxidoreductases; D045726:Metalloproteases; D001205:Ascorbic Acid