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Title: Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

Abstract

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCL/sub 4/) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine amino-transferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VHM) in CCl/sub 4/-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VHM stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl/sub 4/ injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve, possibly by affecting liver metabolism more than the blood flow change to the liver.

Authors:
;
Publication Date:
Research Org.:
Ehime Univ. School of Medicine (Japan)
OSTI Identifier:
5284506
Resource Type:
Journal Article
Resource Relation:
Journal Name: Life Sci.; (United States); Journal Volume: 42:19
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; AMINOTRANSFERASES; ENZYME ACTIVITY; CARBON TETRACHLORIDE; TOXICITY; HYPOTHALAMUS; BIOLOGICAL FUNCTIONS; LIVER; BLOOD FLOW; PATHOLOGICAL CHANGES; NITROSAMINES; NERVES; RATS; AMINES; ANIMALS; BODY; BRAIN; CENTRAL NERVOUS SYSTEM; CHLORINATED ALIPHATIC HYDROCARBONS; DIGESTIVE SYSTEM; ENZYMES; FUNCTIONS; GLANDS; HALOGENATED ALIPHATIC HYDROCARBONS; MAMMALS; NERVOUS SYSTEM; NITROGEN TRANSFERASES; NITROSO COMPOUNDS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; RODENTS; TRANSFERASES; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology

Citation Formats

Iwai, M., and Shimazu, T. Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats. United States: N. p., 1988. Web. doi:10.1016/0024-3205(88)90021-5.
Iwai, M., & Shimazu, T. Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats. United States. doi:10.1016/0024-3205(88)90021-5.
Iwai, M., and Shimazu, T. Fri . "Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats". United States. doi:10.1016/0024-3205(88)90021-5.
@article{osti_5284506,
title = {Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats},
author = {Iwai, M. and Shimazu, T.},
abstractNote = {The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCL/sub 4/) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine amino-transferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VHM) in CCl/sub 4/-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VHM stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl/sub 4/ injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve, possibly by affecting liver metabolism more than the blood flow change to the liver.},
doi = {10.1016/0024-3205(88)90021-5},
journal = {Life Sci.; (United States)},
number = ,
volume = 42:19,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 1988},
month = {Fri Jan 01 00:00:00 EST 1988}
}
  • >Urinary levels of formaldehydogenic steroids (FGS) in rats with liver injury induced by carbon tetrachloride showed a tendency to increase in the acute stage of cirrhosis 4 to 8 weeks later and decreased slightly in the chronic stage 17 to 28 weeks later. In the late stage of cirrhosis the response of urinary FGS to ACTH injection was diminished. Rats treated with dimethylaminoazobenzene (to produce hepatomas) excreted large amounts of FGS in the intermediate stage (8 months later) and the response of urinary FGS to ACTH injection was nearly normal. Urinary FGS levels were not decreased in the course ofmore » experiment. In rats with liver injury caused by ethionine the urinary FGS level was decreased markedly at the initial stage of the experiment, and the response of urinary FGS to ACTH was barely demonstrable. This suggests that the adrenocortical activity is reduced in rats whose liver is injured by ethionine. Hypothalmic lesions in other rats generally caused a marked decrease of the urinary FGS. In rats exposed to 900-r whole-body x radiation, urinary FGS decreased gradually after the 3rd day, and increased transiently before death. Response of urinary FGS to ACTH in the rats irradiated by 900 r of x rays or Co/sup 60/ gamma rays was somewhat delayed, particularly on the 5th day after exposure. In rats irradiated with 600 r of x rays, no change of urinary FGS excretion was found, and the response of urinary FGS to ACTH was normal. In the rats irradiated by lethal dose (900 r) of gamma rays, prolongation of life was effected by subcutaneous injection of 4 units of ACTH on the 2nd day after exposure. The results suggest an increased demand for adrenocortical hormone shortly after lethal irradiation. (TCO)« less
  • Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After /sup 3/H-estradiol (/sup 3/H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of /sup 3/H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females withmore » ARC lesions had very few /sup 3/H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although /sup 3/H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell.« less
  • In this study, quantitative assessment of the synergistic and independent effects of estradiol and progesterone on protein synthesis in the ventromedial hypothalamus (VMN) and the preoptic area (POA) was accomplished using in vitro 35S-methionine and 35S-cystein labeling, two-dimensional gel electrophoresis, and computerized densitometry. Ovariectomized (OVX) rats were divided into four groups. Group 1 was implanted with estradiol (E) capsules for 6 hr and injected with progesterone (P; 0.1 ml, 5 mg/ml propylene glycol) at 20 hr. Group 3 was sham-implanted for 6 hr and injected with 0.01 ml P at 20 hr. Group 4 was sham-planted for 6 hr andmore » injected with vehicle alone at 20 hr. All animals were sacrificed at 24 hr. A number of proteins in both VMN and POA were found to be increased or decreased in labeling by E plus P, E alone, and P alone. Two important synergistic effects of the hormones were found. First, the effects of E on labeling of several proteins in both brain regions were countered by P, and conversely, the effects of P on labeling of several proteins in both brain regions were countered by E. Second, E priming increased the number of proteins affected in labeling by P in both brain regions. Comparison of the effects of E and P on proteins in the VMN and POA indicated that the populations of proteins affected in labeling were markedly different. These results begin to clarify the mechanism in which E and P affect neuronal functioning in two regions involved in the control of reproduction and lend support to the hypothesis that gonadal steroids accomplished their action on brain tissue via a mechanism that is partly unique to the brain region.« less