Inhibition of experimentally induced cirrhosis in rats by hypothyroidism
Authors: R Oren
Journal: Hepatology (1996)

P õ .0001),indicating that the hypothyroid TAA-treated The coexistence of hyperkinetic circulation, hyperrats were less portal hypertensive.These results suggest metabolism, and hyperactivity of the sympathetic nerthat induced hypothyroidism can inhibit, whereas hyvous system is encountered in both cirrhosis and hyperperthyroidism can aggravate, the development of cirthyroidism.Several drugs, such as propylthiouracil and rhosis in a rat model.(HEPATOLOGY 1996;24:419-423.)propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis.We investigated the ef-Cirrhosis represents a dynamic biphasic process deterfects of experimentally induced hypo-and hyperthyroidmined by progressive fibrosis and severe distortion of normal ism on the development of cirrhosis induced in rats by lobular architecture because of regenerative nodules or pseuthioacetamide (TAA).We specifically examined whether dolobules. 1To date, there is no satisfactory medical treatment hypothyroidism could prevent and hyperthyroidism for preventing or reversing the fibrotic process. 2,3could aggravate liver damage.Hypothyroidism inducedThe effect of thyroid status on the induction, clinical course, by methimazole (MMI, 0.04%), propylthiouracil (PTU and survival of both animals and humans with various liver 0.05%), and by thyroidectomy was confirmed by a signifidiseases has received very little attention.However, there is cant elevation of thyroid-stimulating hormone (TSH) evidence that such an effect exists: propranolol, the most levels.Hyperthyroidism (decreased TSH levels) was inpotent beta blocker used in the treatment of portal hypertenduced by eltroxin (ELT:50 mg/kg).5][6] Propylthiogical-TAA), and hyperthyroid (4 groups: ELT 1.5 months uracil (PTU), the drug of choice for thyrotoxicosis, was proand 3 months, and ELT-TAA for 1.5 months and 3 posed as a possible therapeutic modality for alcoholic liver months).Hepatic fibrosis (scored from 0 to 3) was signifidisease. 7Moreover, recently, it has been shown that clinical cantly reduced (P õ .0001) in hypothyroid rats as comhypothyroidism was extremely rare even after 4 years of PTU pared with euthyroid controls, and was aggravated in treatment. 8We have recently shown in a rat model of portal TAA-treated hyperthyroid rats (P õ .0001).Quantitative vein ligation, that induced hypothyroidism was followed by microscopic analysis of liver biopsy specimens from all amelioration of the hyperdynamic circulation and reduction groups confirmed the semiquantitative histopathologiof the portal pressure. 9cal scores (P õ .001).Direct intrasplenic pressure mea-The present study was conducted to find out whether hyposurement revealed a significant portal pressure elevathyroidism could prevent hepatic damage in a rat model of tion in the TAA and the ELT-treated rats (from 4.7 { 0.1 liver cirrhosis.To rule out a direct drug effect, we used two in the euthyroid group to 8.1 { 2.3 and 10.2 { 2.1 and different antithyroid drugs, methimazole (MMI) and PTU, as 12.5 { 1.6 in the TAA, ELT and ELT-TAA groups, respecwell as surgical thyroidectomy; we also examined the effect tively).However, in the hypothyroid-TAA groups, the of hyperthyroidism, eltroxin (ELT) induced, on the developportal pressure was found to be within the euthyroid ment of thioacetamide (TAA)-induced hepatic damage.normal range (4.6 { 1.2 and 5.8 { 0.6 in the PTU-TAA MATERIALS AND METHODS and surgical-TAA, respectively).After 12 weeks, the mean spleen weight of rats receiving only TAA was sig-Animals.Female Wistar rats (200-250g), obtained from Tel Aviv nificantly higher than the TAA-treated hypothyroid rats University Animal Breeding Center, Tel Aviv, Israel, were kept in the animal breeding house of the Wolfson Medical Center and fed a Purina rodent chow ad libitum.TAA was obtained from Sigma Chemical Co.(St.Louis, MO).