Hepatoprotective effect of Arazyme on CCl4-induced acute hepatic injury in SMP30 knock-out mice.
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.
Park
Jin-Kyu
JK
Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Jeong
Da-Hee
DH
Park
Ho-Yong
HY
Son
Kwang-Hee
KH
Shin
Dong-Ha
DH
Do
Sun-Hee
SH
Yang
Hai-Jie
HJ
Yuan
Dong-Wei
DW
Hong
Il-Hwa
IH
Goo
Moon-Jung
MJ
Lee
Hye-Rim
HR
Ki
Mi-Ran
MR
Ishigami
Akihito
A
Jeong
Kyu-Shik
KS
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
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