Liver cell necrosis and regeneration following injections of carbon tetrachloride. Effects of the thyrotropin-releasing hormone and somatostatin.

Mice were given 10 micrograms somatostatin or 25 micrograms TRH intraperitoneally 10 min before s.c. injection of 2 or 20 mg CCl4. The extent of liver cell necrosis and nuclear size were measured by the electronic Mini Mop method and the extent of necrosis and nuclear pleomorphism were estimated by a visual linear analogue scale of 100 mm, and compared to plasma concentrations of ASAT and ALAT. Pre-treatment with TRH or somatostatin resulted in significant reduction in the extent of necrosis 24 h after CCl4-injections (25%), with a lowering of ASAT from 13209 +/- 2955 U/l to 5144 +/- 924 after TRH and to 6186 +/- 966 after somatostatin, and of ALAT from 14343 +/- 3209 to 7718 +/- 1727 and 6494 +/- 1253 U/l, respectively. After 3 days the necroses were reduced from 16.5 +/- 1.7% by the Minimop method to 1.4 +/- 0.5% (90%) in mice given CCl4 alone, and from 12.3 +/- 1.7% to 3.8 +/- 1.2% in mice pretreated with TRH, and from 12.3 +/- 1.8% to 3.8 +/- 1.7% (70%) in mice pretreated with somatostatin. The plasma concentrations of ASAT and ALAT were reduced correspondingly. After 5 days no necroses were seen, and the plasma ASAT and ALAT were normal. After 6 months of weekly injections of TRH or somatostatin before 20 mg CCl4 the liver cell nuclear size (10.5 and 9.7 0.3 mu 2) was similar to that after CCl4 alone (9.7 0.3 mu 2), and twice that of controls (4.6-5.4 0.1 mu 2). Liver cell necrosis was not seen. The plasma concentrations of ASAT (131 8.6-162 11.3) and ALAT (98 8-104 9 Iu/l) were similarly 2-3 times those in controls. TRH and somatostatin thus reduced liver cell injury and delayed regeneration after single injections of CCl4. After 6 months of weekly injections no effects were observed.