Retrospective evaluation of serum ornithine carbamyltransferase activity as an index of hepatotoxicity in toxicological studies with rats.
The sensitivity of elevated serum ornithine carbamyltransferase (OCT) as an index of hepatotoxicity in rats was assessed in different studies conducted over a number of years and originally designed to examine the toxicity or carcinogenicity of a variety of test chemicals and diets. Changes in serum OCT activities were compared with the more widely used clinical endpoints, alanine aminotranserase (ALT) and aspartate aminotransferase (AST). In the first study, rats received a single oral dose of the hepatotoxic and hepatocarcinogenic fungal toxin aflatoxin B(1) (AFB(1)). The increase in enzyme levels between control and AFB(1)-treated rats was greater for serum OCT than for ALT or AST. This response was similar to the changes in serum enzyme levels in studies where rats ingested a hepatotoxic and hepatocarcinogenic choline deficient (CD) diet. When rats were exposed to the hepatotoxic and nephrotoxic fungal toxin fumonisin B(1) (FB(1)) by intraperitoneal injection for 6 days, serum AST and ALT were significantly elevated above control levels while OCT was unaffected. The peroxisome proliferator ciprofibrate caused elevated ALT and AST but not OCT at week 52 of dietary exposure, after the development of liver nodules and tumours. Of the two liver-specific enzymes examined in all of the studies, ALT was more consistently predictive of hepatotoxicity than OCT.
Bondy
G S
GS
Toxicology Research Division, 2204D2, Food Directorate, Health Protection Branch, Health Canada, 2E Banting Building, Ottawa, Canada. genevieve_bondy@hc-sc.gc.ca
Armstrong
C L
CL
Curran
I H
IH
Barker
M G
MG
Mehta
R
R
D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001377:Azaserine / Q000008:administration & dosage / Q000633:toxicity*; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000633:toxicity*; D002796:Choline Deficiency / Q000201:enzymology; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D058607:Fibric Acids; D037341:Fumonisins; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity; D009954:Ornithine Carbamoyltransferase / Q000187:drug effects* / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000008:administration & dosage / Q000633:toxicity; D011237:Predictive Value of Tests; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies
D000903:Antibiotics, Antineoplastic; D002264:Carboxylic Acids; D058607:Fibric Acids; D037341:Fumonisins; D009183:Mycotoxins; D020025:Peroxisome Proliferators; C056933:fumonisin B1; D002995:Clofibric Acid; D001377:Azaserine; D016604:Aflatoxin B1; D009954:Ornithine Carbamoyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C019304:ciprofibrate