The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats.
S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione (GSH) donor, has been studied mechanistically in vitro, in humans with clinical liver disease, and in experimental animal models of liver disease. Collective findings encourage its therapeutic use in necroinflammatory and cholestatic liver disorders. A chronic longitudinal study (pre- and posttreatment parameters compared) was undertaken with 15 clinically healthy cats given a stable 1,4-butanedisulfonate (S'S isomer) SAMe salt (enteric coated tablets providing 180 mg SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine physical and clinicopathologic assessments, red blood cell (RBC) osmotic fragility, liver function and histology, hepatic concentrations of reduced GSH (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe concentrations were evaluated. SAMe administered PO significantly increased plasma SAMe concentrations, and peak concentrations usually occurred 2-4 hours after dosing. Chronic SAMe administration did not change peak or cumulative plasma SAMe concentrations and did not [corrected] cause overt signs of toxicity. A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P < .002], liver GSH increased 35% [P < .002], liver RGSH: GSSG ratio increased 69% [P < .03]) and improved RBC resilience to osmotic challenge (P < .03) were observed. Results prove that this SAMe PO product is enterically available and suggest that it imparts biologic effects that might be useful for attenuating systemic or hepatic oxidant challenge.
Center
S A
SA
Department of Clinical Sciences and of Population Medicine and Diagnostic Services, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. sac6@cornell.edu
Randolph
J F
JF
Warner
K L
KL
McCabe-McClelland
J
J
Foureman
P
P
Hoffmann
W E
WE
Erb
H N
HN
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000502:physiology; D002415:Cats / Q000378:metabolism*; D004334:Drug Administration Schedule / Q000662:veterinary; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008137:Longitudinal Studies; D009996:Osmotic Fragility / Q000187:drug effects; D010084:Oxidation-Reduction; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000494:pharmacology*; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D012436:S-Adenosylmethionine; D005978:Glutathione; D019803:Glutathione Disulfide