Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice.
We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6, 12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.
Kume
Eisuke
E
Exploratory Toxicology and DMPK Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan. e-kume@tanabe.co.jp
Fujimura
Hisako
H
Matsuki
Naoaki
N
Ito
Masahito
M
Aruga
Chinami
C
Toriumi
Wataru
W
Kitamura
Kazuyuki
K
Doi
Kunio
K
D000208:Acute Disease; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000473:pathology*; D005704:Gallbladder / Q000187:drug effects / Q000473:pathology; D005705:Gallbladder Diseases / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D006943:Hyperglycemia / Q000139:chemically induced; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors; D014456:Ulcer / Q000139:chemically induced / Q000150:complications / Q000473:pathology
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin