title: Lack of protective effect of D-003, a mixture of high-molecular-weight primary acids from sugar cane wax, on liver damage induced by galactosamine in rats.
abstract: D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, wherein octacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and prevents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- and paracetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galactosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this study was to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigated the effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive control group, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine (800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats were sacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the characteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepatocytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increase the percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for preventing the hepatic injury induced with galactosamine. Likewise, D-003 failed to change the content of necrotic and lipid-rich hepatocytes relative to positive controls. It is concluded that D-003 did not protect against the histological changes of galactosamine-induced hepatotoxicity.
authors.affiliation: Center of Natural Products from the National Center for Scientific Research, Havana City, Cuba. clinica@enet.cu
authors.forename: Miriam
authors.initials: M
authors.lastname: Noa
authors.forename: Sarahí
authors.initials: S
authors.lastname: Mendoza
authors.forename: Rosa
authors.initials: R
authors.lastname: Mas
authors.forename: Nilda
authors.initials: N
authors.lastname: Mendoza
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005227:Fatty Acids / Q000627:therapeutic use*; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology; D002479:Inclusion Bodies / Q000737:chemistry; D008055:Lipids / Q000032:analysis; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D008055:Lipids; D005688:Galactosamine