INHIBITION OF EXPERIMENTALLY-INDUCED CIRRHOSIS IN RATS BY HYPOTHYROIDISM

The coexistence of hyperkinetic circulation, hypermetabolism, and hype ractivity of the sympathetic nervous system is encountered in both cir rhosis and hyperthyroidism, Several drugs, such as propylthiouracil an d propranolol, that are beneficial for treating some patients with chr onic liver diseases are also prescribed for the treatment of thyrotoxi cosis, We investigated the effects of experimentally induced hypo and hyperthyroidism on the development of cirrhosis induced in rats by thi oacetamide (TAA), We specifically examined whether hypothyroidism coul d prevent and hyperthyroidism could aggravate Liver damage, Hypothyroi dism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%) , and by thyroidectomy was confirmed by a significant elevation of thy roid-stimulating hormone (TSH) levels, Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 mu g/kg). Thirteen groups of 1 0 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups: ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months), Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) i n hypothyroid rats as compared with euthyroid controls, and was aggrav ated in TAA-treated hyperthyroid rats (P < .0001), Quantitative micros copic analysis of Liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001), Direct intraspl enic pressure measurement revealed a significant portal pressure eleva tion in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euth yroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TA A, ELT and ELT-TAA groups, respectively), However, in the hypothyroid- TAA groups, the portal pressure was found to be within the euthyroid n ormal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-T AA, respectively), After 12 weeks, the mean spleen weight of rats rece iving only TAA was significantly higher than the TAA-treated hypothyro id rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive, These results suggest that induced hypo thyroidism can inhibit, whereas hyperthyroidism can aggravate, the dev elopment of cirrhosis in a rat model.