Effects of calcium antagonist diltiazem on liver calcium content and necrosis of hepatocytes in rats following treatment with CCL4.
To study the relationship between the changes in hepatocytes and calcium contents in the liver of 42 rats treated with CCl4 and the effect of a calcium antagonist diltiazem on the liver injury, we determined liver calcium content, serum alanine aminotransferase (ALT), and serum levels of triiodothyronine (T3), thyroxine (T4), the T3/T4 ratio, and calcium before and 6 to 72 hr after treatment with a single oral dose of CCl4 (0.5 ml/kg) in 21 rats (Group I) and in 21 rats treated with diltiazem (10 mg/kg) intraperitoneally three times, 24 hr before, simultaneously with, and 24 hr after administration of the same doses of CCl4 (Group II). The maximum calcium content in Group I was 259.7 +/- 53.3 micrograms/g wet weight at 24 hr after treatment, whereas it was 113.0 +/- 51.1 micrograms/g wet weight in Group II, and a significant difference was seen between them (p less than 0.05). The ALT levels in both groups elevated after 18 to 24 hr and a significant difference was also found between the two levels at 24 hr (p less than 0.05). The T3/T4 ratio in Group I decreased immediately, but increased later. The ratio in Group II maintained the level before treatment. Correlation between the calcium content and the grade of centrilobular necrosis was significantly seen in Group I (r = 0.82, p less than 0.001), but was not found in Group II. The grade of centrilobular necrosis appeared to be more severe at 24 to 48 hr in Group I than in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)
Itoh
S
S
Department of Medicine, Saitama Medical School, Japan.
Gohara
S
S
Matsuo
S
S
Yamaba
Y
Y
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D000410:Alanine Transaminase; D004110:Diltiazem; D002118:Calcium