Partial hepatectomy

Schmidt The liver is sort of an example, and the practical answer to the question of why it is useful to know is because sometimes we want to reconstitute livers. When you do a two-thirds partial hepatectomy all the cells divide. Suppose you push this to a limit and take out 90% of a liver, the hope is that there is something called a liver stem cell which is at something called GO, which is capable of reconstituting 90% as opposed to 67%. Is this a practical definition of GO ... 

Brooks, A. L., Benjamin, S. A., Jones, R. K. and McClellan, R. O. (1972). Effect of l44Ce-ll4Pr and partial-hepatectomy on the production of liver tumors in the Chinese hamster, page 241 in Fission Product Inhalation Program Annual Report 1971-1972, Report No. LF-45 (Lovelace Foundation, Albuquerque, New Mexico). 

Delaney, B. and Kaminski, N.E., Liver-immune interactions induced by hepatic regeneration similarities between partial hepatectomy and chemically mediated hepatotoxicity, in Experimental Immunotoxicology, Smialowicz, R J. and Holsapple, M.P., Eds., CRC Press, Boca Raton, 1996. 

Bell AN, Young RA, Lockard VG, et al. 1988. Protection of chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality by partial hepatectomy. Arch Toxicol 61 392-405. 

Dolak JA, Britton R, Glende EA Jr, et al. 1987. Chlordecone does not interfere with hepatic repair after carbon tetrachloride or partial hepatectomy. J Biochem Toxicol 2 57-66. 

Two studies were located in which rats received di- -octylphthalate dietary exposures of 250 or 500 mg/kg/day for either 10 or 26 weeks (Carter et al. 1992 DeAngelo et al. 1986). Five male rats were first initiated with a single subcarcinogenic intraperitoneal dose of diethylnitrosamine (30 mg/kg), followed by partial hepatectomy. Di-w-octylphthalatc caused substantial increases in gamma-glutamyltranspeptidase (GGT) positive liver foci when compared with the controls (e.g., from 3.5 to 20.8 foci/cm2) or in hepatic levels of marker enzymes for altered cellular foci (GGT and glutathione 5-transferase [GST]). Only a slight increase (threefold) was observed for carnitine acetyltransferase (CAT) activity, a marker for peroxisome... 

Rats exposed to di-n-octylphthalate in the diet for either 10 or 26 weeks following a single subcarcinogenic intraperitoneal injection of diethylnitrosamine and partial hepatectomy exhibited increases in GGT-positive liver foci that were not associated with peroxisome proliferation (Carter et al. 1992 DeAngelo et al. 1986). These results suggest that di-n-octy lph thal ate may be effective in promoting preneoplastic lesions in the rat liver, probably by a mechanism that does not rely on peroxisome proliferation. 

M. Jokanovic, Liver Esterases and Soman Toxicity in the Rat Following Partial Hepatectomy , Biochem. Pharmacol. 1990, 39, 797-799. 

Dibromoethane was administered orally in corn oil to Sprague-Dawley rats in doses up to 120 mg/kg body weight in an initiation protocol that included partial hepatectomy (Milks et al. 1982). This treatment did not cause an increase in g-glutamyl transpeptidase (GGT) positive foci after 2 months. When 1,2-dibromoethane was orally administered in corn oil at doses of 10 or 30 mg/kg in a promotion protocol with N-nitrosodiethylamine as an initiator, there was a significant increase in production of GGT positive foci after 2 months. Based on their results, the authors speculated that... 

In another liver foci study using Sprague-Dawley (Crl CD) rats, 1,2-dibromoethane in corn oil given by gavage was used as an initiator. Two dose regimens were used 75 mg/kg 1,2-dibromoethane at 0 and 24 hours or corn oil at 0 hours and 75 mg/kg 1,2-dibromoethane at 24 hours. Partial hepatectomies and phenobarbital in drinking water also were part of the protocol. With this system, at 16 months, 1,2-dibromoethane-exposed rats had increased numbers of foci of hepatic cellular alteration. Rats that received the two doses of 1,2-dibromoethane had increased numbers of nodules on hematoxylin and eosin-stained sections as well as increased number and size of GGT positive foci (Moslen 1984). These results indicate that 1,2-dibromoethane can act as an initiator. 

Under normal conditions, many of the enzymes involved in the pathway for pyrimidine biosynthesis de novo may not operate at maximum efficiency but rather exist in an inhibited state. This inhibition is released during the course of regeneration (for example after partial hepatectomy [133] or castration... 

To assess this methodology s diagnostic capability in impaired livers, a partial hepatectomy was surgically performed on three rats, followed by measurement of the time dependence of fluorescence at the ear pre- and post-injection of ICG. Fig. 10 depicts the comparison of clearance rates between normal and impaired functioning livers. The time constants for the rats with normal and dysfunctional livers are shown in Table 1. The difference between the animals with normal and impaired livers is huge and quantifiable. 

Normal Rats with normal functioning liver. Abnormal Rats with partial hepatectomy. 

Cai Z, Mehendale HM. 1991b. Prestimulation of hepatocellular regeneration by partial hepatectomy decreases toxicity of carbon tetrachloride in gerbils. Biochem pharmacol 42 633-644. 

Kodavanti PR, Joshi UM, Young RA, et aj. 1989b. Protection of hepatotoxic and 4 by partial hepatectomy. Toxicdl Pathol 17 494-505. 

Lindroos PM, Zarnegar R, Michalopoulos GK. 1990. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DMA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration. Hepatology 13 743-750. 

Suda H, Masui T, Ikawa E, et al. 1987. Compared promoting potential of D- galactosamine, carbon tetrachloride and partial hepatectomy in rapid induction of prenaoplastic liver lesions in the rat. Cancer Lett 37 163-171. 

AAF, 2-acetylaminofluorene BBN, W-butyl-W-(4-hydroxybutyl)nitrosamine EHEN, W-ethyl-W-hydroxyethylnitrosamine NDEA, W-nitrosodiethylamine F, female M, male i.p., intraperitoneal injection i.g., intragastric PEI, partial hepatectomy... 

PH, partial hepatectomy AAF, 2-acetylaminofluorene CCI4, carbon tetrachloride... 

Groups of 18-20 male Fischer rats (weighing 160 g) were given a single intra-peritoneal injection of 200 mg/kg bw NDEA. Two weeks later, they were fed a diet containing 3000 ppm di(2-ethylhexyl) phthalate [purity unspecified] for six weeks. At week 3, they were subjected to a partial hepatectomy. All rats were killed at week 8. Di(2-ethylhexyl) phthalate-treated rats had no increase in foci staining positively for glutathione S-transferase placental form (8.5 per cm versus 11.6 for NDEA alone) (Ito etal., 1988). 

Treatment of neonatal animals, or those subjected to partial hepatectomy, with single doses of dimethylnitrosamine, leads to hepatic tumors, as in these cases the liver cells are actively dividing and are more susceptible. It has been found that the liver cells in culture are susceptible at particular stages in the cell cycle. 

Two groups of 14 and 15 male Fischer 344 rats, six weeks of age, were administered a single intraperitoneal injection of 200 mg/kg bw NDEA in 9% (w/v) saline. After a two-week recovery period, rats were given either 10 000 mg caprolactam [purity im-specified]/kg diet (ppm) or basal diet for six weeks. At week 3, all rats were subjected to a two-thirds partial hepatectomy and killed at week 8. Quantitative analysis of GST-P-positive foci of the liver was performed. There were no significant differences in either the numbers or areas of GST-P-positive foci between the caprolactam-treated group and the controls (Hasegawa Ito, 1992). 

Groups of 7-10 male Sprague-Dawley rats, weighing 200 g, were administered catechol (purity, > 98%) at concentrations of 0 or 100 mg/kg in the diet for six weeks beginning one week after partial hepatectomy and intraperitoneal injection of 30 mg/kg bw /V-nitrosodietliylamine to initiate liver carcinogenesis. Catechol after initiation did not increase the multiplicity of liver enzyme-altered (y-glutamyltranspeptidase) foci (Stenius et al., 1989). 

Positive when mice were treated intraperitoneally with 180 mg/kg bw/day epichlorohydrin Positive only when mice received partial hepatectomy before treatment... 

In a single study, epichlorohydrin bound to DNA of mice and rats treated in vivo. One study reported that sister chromatid exchanges were induced in the bone marrow of partially hepatectomized CBA/J mice treated with epichlorohydrin by a single intraperitoneal injection. Sister chromatid exchange frequencies in mice that did not receive partial hepatectomy before treatment with epichlorohydrin were comparable to the control frequencies. One of two studies reported that epichlorohydrin induced chromosomal aberrations in mouse bone marrow. Positive results were also reported for epichlorohydrin in the mouse host-mediated assay in one of three studies. In single studies, epichlorohydrin caused sperm head abnormalities in rats but not mice. It did not induce micronuclei or dominant lethal mutations in mice in vivo. 

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