Complete Liver Regeneration in One–Stage 90% Hepatectomized Rats Treated With Testosterone

Abstract

Major hepatectomy can be considered as a possible treatment for liver metastases or primary cancer of the liver. Unfortunately, the extent of liver resection must be kept below 80% for regeneration to occur. When 90% hepatectomy is performed in the rat, there is no regeneration of the 10% remnant. Instead, the major finding is overwhelming steatosis, and the animals do not survive beyond the 40th hr posthepatectomy (1,2). Since testosterone has been reported to reduce liver fat content after partial hepatectomy (3), we decided to ascertain whether, after 90% hepatectomy in the rat, testosterone would reduce steatosis and thereby allow regeneration to occur with ultimate survival of the animal. Histological evidence suggests that testosterone offers protection against steatosis. Moreover, the liver remnant was found to regenerate, accompanied by increased liver weight and survival.Two groups of 50 rats underwent 90% hepatectomy, one treated with testosterone oenanthate (Group 2), the other untreated (Group 1). A survival study was undertaken in 20 rats of each group. The others were sacrificed at different times posthepatectomy to determine liver remnant weight and histology.Survival time was strikingly different for the two groups: in Group 1, 100% of rats died before the 40th hr; in Group 2, 80% survived beyond the 40th hr, among these, 50% presented a normal life span. Moreover, as shown in Table 1, liver remnant weight was significantly higher in the treated group, even as early as 24 hr posthepatectomy. The testosterone-treated rats which survived showed marked liver remnant mass restoration: 400% at 72 hr and 600% at 96 hr posthepatectomy.

A Good Model of Hepatic Failure after Excessive Hepatectomy in Mice

“…is not yet well understood, and so, to clarify it, numerous animal models have been established [1][2][3][4][5][6][7][8][9][10][11][12]. Previously, we clearly demonstrated that 90%-hepatectomy is a safety limit for rat hepatectomy.…”

Anabolic‐androgenic steroid treatment of liver diseases

“…A reproducible sex difference has been observed in animal studies, showing that male sex protects against liver lipid accumulation induced by noxious substances and partial hepatectomy (90,91,92,93,94,95). In accordance, AAS decrease liver lipid accumulations induced by ethionine (93,96,97), carbon tetrachloride (98,99, loo), oxyterracin (101), rifampicin (102), ovariectomy (102, 103), acute and chronic ethanol administration (45, 92, 104) and partial hepatectomy (63,64,105). In contrast, AAS seem to have little or no effect on liver lipids in normal rats (102,103).…”

“…Further, AAS regulates hepatic estrogen receptors Castration and/or AAS administration do not affect hepatic DNA content in animals (57, 58, 59,60) and man (61), and AAS are not considered probable regulators of rat liver regeneration (62). In recent studies, pretreatment with testosterone enanthate significantly improved survival of rats subjected to 90% hepatectomy (63,64). In these studies hepatic DNA was not determined, and the mechanism is not clearly understood.…”

Analysis of Gene Expression Profiles in Fatal Hepatic Failure After Hepatectomy in Mice

“…Many rat models have been established to clarify the mechanism of fatal hepatic failure after excessive hepatectomy [1][2][3]. We developed a new technique of hepatectomy in rats, a procedure that enabled all 90%-hepatectomized rats to survive, while all 95%-hepatectomized rats died of hepatic failure within 96 h [4].…”