Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice.
In the search of hepatoprotective agents from natural sources, alpha- and beta-amyrin, a triterpene mixture isolated from the trunk wood resin of folk medicinal plant, Protium heptaphyllum was tested against acetaminophen-induced liver injury in mice. Liver injury was analysed by quantifying the serum enzyme activities and by histopathological observations. In mice, acetaminophen (500 mg/kg, p.o.) caused fulminant liver damage characterized by centrilobular necrosis with inflammatory cell infiltration, an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, a decrease in hepatic glutathione (GSH) and 50% mortality. Pretreatment with alpha- and beta-amyrin (50 and 100 mg/kg, i.p. at 48, 24, and 2 h before acetaminophen) attenuated the acetaminophen-induced acute increase in serum ALT and AST activities, replenished the depleted hepatic GSH, and considerably reduced the histopathological alterations in a manner similar to N-acetylcysteine, a sulfhydryls donor. Also, the acetaminophen-associated mortality was completely suppressed by terpenoid pretreatment. Further, alpha- and beta-amyrin could potentiate the pentobarbital (50 mg/kg, i.p.) sleeping time, suggesting the possible suppression of liver cytochrome-P450. These findings indicate the hepatoprotective potential of alpha- and beta-amyrin against toxic liver injury and suggest that the diminution in oxidative stress and toxic metabolite formation as likely mechanisms involved in its hepatoprotection. In conclusion, this study supports the traditional use of Protium heptaphyllum resin as a medicinal agent and suggests the feasibility of developing herbal drugs for treatment of liver disorders.
Oliveira
Francisco A
FA
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel Nunes de Melo 1127, Porangabussu Caixa Postal 3157, 60430-270 Fortaleza, Ceará, Brazil.
Chaves
Mariana H
MH
Almeida
Fernanda R C
FR
Lima
Roberto C P
RC
Silva
Regilane M
RM
Maia
Juliana L
JL
Brito
Gerly Anne A C
GA
Santos
Flávia A
FA
Rao
Vietla Satyanarayana
VS
D000082:Acetaminophen; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D029403:Burseraceae / Q000737:chemistry*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D010424:Pentobarbital / Q000494:pharmacology; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D012116:Resins, Plant / Q000737:chemistry / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D014315:Triterpenes / Q000627:therapeutic use*
D020011:Protective Agents; D012116:Resins, Plant; D014315:Triterpenes; D000082:Acetaminophen; D009828:Oleanolic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D010424:Pentobarbital; C036380:beta-amyrin