Enhancement by Estradiol 3-Benzoate in Thioacetamide-Induced Liver Cirrhosis of Rats

Abstract

As part of an investigation on the role of estrogen in liver disease, we tested the effects of estradiol-3-benzoate (EB) in the thioacetamide (TAA)-induced rat liver cirrhosis model. Male F344 rats (n = 100) were divided into six groups. Animals of groups 1-4 received TAA (0.03% in drinking water) for 12 weeks, and groups 5 and 6 served as controls without TAA. For the exposure period, EB pellets were implanted subcutaneously to give doses of 0 (groups 1 and 5), 1 (group 2), 10 (group 3), and 100 mug (groups 4 and 6) simultaneously. All animals were sacrificed at week 12. Significant increase of liver cirrhosis, liver weight, collagen content, and lipid peroxidation in the livers was evident in groups 3 and 4 (p < 0.05) compared with group 1. Formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly elevated in group 4 (p < 0.01), along with expression of alpha-smooth muscle actin (alpha-SMA) and stellate cell activation-associated protein (STAP), as determined by RT-PCR analysis (p < 0.01). However, there were no differences in liver weight, collagen content, lipid peroxidation, 8-OHdG formation, and alpha-SMA and STAP mRNA expression between groups 5 and 6. We conclude that EB treatment enhances TAA-induced cirrhosis, associated with increase of oxidative stress and activation of hepatic stellate cells.

Signal profile on Gd-EOB-DTPA-enhanced MR imaging in non-alcoholic steatohepatitis and liver cirrhosis induced in rats: correlation with transporter expression

“…The administration of thioacetamide (TAA) to rats is a wellestablished model of chemically induced liver cirrhosis, and the cirrhosis induced by TAA is claimed to be morphologically well defined and uniform, reflecting the major features of human disease [22][23][24][25]. In addition to TAA rats, we used choline-deficient diet-induced NASH rats that showed diffuse macrovesicular steatosis, various levels of inflammation and fibrosis.…”

“…The rats in the cirrhosis group received 0.03% thioacetamide (Nacalai tesque, Kyoto, Japan) solution as drinking water for 12 weeks to induce liver cirrhosis (TAA group) [22][23][24][25] and were divided into two subgroups as follows: Group 1 for MRI (n=7) and Group 2 for polymerase chain reaction (PCR, n=5). The rats in the two NASH groups (7-and 10-week groups) were fed a cholinedeficient diet (product No.…”

Thioacetamide Intoxication Triggers Transcriptional Up-Regulation but Enzyme Inactivation of UDP-Glucuronosyltransferases

“…Primers for rat UGT1A1, UGT1A6, UGT2B1, and glyceraldehyde phosphate dehydrogenase (GADPH) were designed using the primer select software (Primer Premier 5.0; PREMIER Biosoft International, Palo Alto, CA) on the basis of previous reports (Nozu et al, 1992;Kang et al, 2005). Sequences of the polymerase chain reaction (PCR) primers are as follows (sense and antisense for each isoform, 5Ј-3Ј, respectively): UGT1A1 (554 bp), ACG AAG TGG TGG TCA TAG CA, CTG TAA GAT TTC AGT GGC AAG; UGT1A6 (270 bp), TGG TGC TAG TGC CAG AAG TCA A, GAG CAT CAA ACT GGT TCT CCC T; UGT2B1 (439 bp), GTC ACG GTT CTT GTA TCT TCG G, GAA CAA CAG GCA CAT AGG AAG G; and GAPDH (352 bp), CGG GAA GCT TGT CAT CAA TGG, GGC AGT GAT GGC ATG GAC TG.…”

“…Thioacetamide (TAA), originally used as a fungicide, is a potent hepatotoxicant and has been widely used in developing experimental liver fibrosis/cirrhosis models mimicking the human liver fibrosis/ cirrhosis (Nozu et al, 1992;Kang et al, 2005). As the largest metabolic organ in biological systems, the liver, endowed with many types of drug-metabolizing enzymes, plays a critical role in the metabolic elimination of many endogenous substances and exogenous toxicants.…”

Estrogen derivatives

“…Other problems to be resolved Unexpectedly, estrogen treatment enhanced fibrosis or cirrhosis in a thioacetamide-induced liver cirrhosis model and BDL rats, associated with an increase in oxidative stress and activation of HSCs [107][108][109]. This difference in action appears to reflect variations in estrogen metabolism and interactions with different hepatotoxins [107].…”