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Efficacy of MK615 for the treatment of patients with liver disorders.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2012 Aug 21; Vol. 18 (31), pp. 4118-26. - Publication Year :
- 2012
-
Abstract
- Aim: To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect.<br />Methods: Wistar rats were administered physiological saline (4 mL/kg) or MK615 solution (4 mL/kg) for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection (ip) of D-galactosamine hydrochloride (D-GalN) (600 mg/kg). Plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and liver tissues were used for histopathological analysis. Fifty-eight patients with liver disorders [hepatitis C (n = 40), non-alcoholic fatty liver disease (n = 15), and autoimmune liver disease (n = 3)] were orally administered commercially available Misatol ME-containing MK615 (13 g/d) daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various biochemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint.<br />Results: D-GalN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GalN, the plasma levels of ALT (475.6 ± 191.5 IU/L vs 225.3 ± 194.2 IU/L, P < 0.05) and AST (1253.9 ± 223.4 IU/L vs 621.9 ± 478.2 IU/L, P < 0.05) in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly decreased compared with pre-intake baseline levels from 103.5 ± 58.8 IU/L to 71.8 ± 39.3 IU/L (P < 0.05) and from 93.5 ± 55.6 IU/L to 65.5 ± 34.8 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 26 (45%) of the 58 patients, while 25 (43%) patients exhibited similar AST level reductions. The chronic hepatitis C group exhibited significant ALT and AST level reductions from 93.4 ± 51.1 IU/L to 64.6 ± 35.1 IU/L (P < 0.05) and from 94.2 ± 55.5 IU/L to 67.2 ± 35.6 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 20 (50%) of the 40 patients. ALT levels in both the combined ursodeoxycholic acid (UDCA) treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GalN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders.<br />Conclusion: These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.
- Subjects :
- Adult
Aged
Aged, 80 and over
Alanine Transaminase metabolism
Animals
Aspartate Aminotransferases metabolism
Chemical and Drug Induced Liver Injury drug therapy
Chemical and Drug Induced Liver Injury metabolism
Chemical and Drug Induced Liver Injury pathology
Disease Models, Animal
Fatty Liver metabolism
Fatty Liver pathology
Female
Galactosamine adverse effects
Hepatitis C metabolism
Hepatitis C pathology
Hepatitis, Autoimmune metabolism
Hepatitis, Autoimmune pathology
Humans
Liver enzymology
Liver pathology
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
Rats
Rats, Wistar
Treatment Outcome
Fatty Liver drug therapy
Hepatitis C drug therapy
Hepatitis, Autoimmune drug therapy
Plant Extracts therapeutic use
Prunus
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 18
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 22919243
- Full Text :
- https://doi.org/10.3748/wjg.v18.i31.4118