scholarly journals Some Biochemical and Histological Effects of 2-Chloroethanol in Rats

1992 ◽  
Vol 1 (3) ◽  
pp. 37-56 ◽  
Author(s):  
Leonard Friedman ◽  
John Scalera ◽  
James E. Keys ◽  
Edmund L. Peters ◽  
Dennis W. Gaines ◽  
...  

The effects of 2-chioroethanol (2-CE) on rat tissue following in vitro and in vivo exposure were studied. At concentrations as low as 2.5 mg/ml, protein synthesis in liver slices was inhibited; at concentrations of 25 mg/ml and above, RNA synthesis and respiration were also impaired. Single oral doses of 2-CE to young adult rats at levels of 15-40 mg/kg body weight depressed liver nonprotein sulfhydryl (GSH) concentration and liver protein but not RNA synthesis. Liver lipid was increased by 7 hr after a single oral dose of 30 mg/kg. The time courses and dose-response relationship for GSH depletion and restoration and for protein synthesis inhibition and recovery were similar. The livers of female rats were more sensitive than the livers of male rats to the effects of 2-CE. Protein synthesis was also depressed in kidneys of 2-CE-treated male rats but at higher doses than those needed for this effect to occur in livers of the same animals. Liver polysome disaggregation also occurred after oral 2-CE doses of 20 mg/kg and greater. The effects of 2-CE on ribosome profiles and protein synthesis were at least partially reversed by concurrent intraperitoneal administration of cysteine. The possible relationship of these findings to a role of GSH in protein synthesis is discussed.

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy


1999 ◽  
Vol 277 (6) ◽  
pp. G1189-G1199 ◽  
Author(s):  
Robert F. Rotundo ◽  
Peter A. Vincent ◽  
Paula J. McKeown-Longo ◽  
Frank A. Blumenstock ◽  
Thomas M. Saba

Fibronectin (Fn) is a major adhesive protein found in the hepatic extracellular matrix (ECM). In adult rats, the in vivo turnover of plasma Fn (pFn) incorporated into the liver ECM is relatively rapid, i.e., <24 h, but the regulation of its turnover has not been defined. We previously reported that cellular Fn (cFn) and enzymatically desialylated plasma Fn (aFn), both of which have a high density of exposed terminal galactose residues, rapidly interact with hepatic asialoglycoprotein receptors (ASGP-R) in association with their plasma clearance after intravenous infusion. With the use of adult male rats (250–350 g) and measurement of the deoxycholate (DOC)-insoluble125I-labeled Fn in the liver, we determined whether the ASGP-R system can also influence the hepatic matrix retention of various forms of Fn. There was a rapid deposition of 125I-pFn,125I-aFn, and125I-cFn into the liver ECM after their intravenous injection. Although125I-pFn was slowly lost from the liver matrix over 24 h, more than 90% of the incorporated125I-aFn and125I-cFn was cleared within 4 h ( P < 0.01). Intravenous infusion of excess nonlabeled asialofetuin to competitively inhibit the hepatic ASGP-R delayed the rapid turnover of both aFn and cFn already incorporated within the ECM of the liver. ECM retention of both125I-aFn and125I-cFn was also less than125I-pFn ( P < 0.01) as determined in vitro using liver slices preloaded in vivo with either tracer form of Fn. The hepatic ASGP-R appears to participate in the turnover of aFn and cFn within the liver ECM, whereas a non-ASGP-R-associated endocytic pathway apparently influences the removal of normal pFn incorporated within the hepatic ECM, unless it becomes locally desialylated.


1992 ◽  
Vol 262 (1) ◽  
pp. E1-E5 ◽  
Author(s):  
A. G. Baillie ◽  
P. J. Garlick

One-year-old adult female rats were fasted for 12 or 36 h followed by a 30-min infusion of insulin. The responses of the fractional rate of protein synthesis (Ks) in the individual muscles (measured in vivo) to fasting were small and mostly nonsignificant. After 12 h of fasting, only the epitrochlearis muscle (ET) showed a significant decrease in Ks, and, even after 36 h of fasting, a significant decrease in Ks was seen in only ET, extensor digitorum longus, and tensor fasciae latae (TFL). After the 36-h fast, infusion of insulin restored the fed Ks in all muscles except TFL. The fiber-type composition of the individual muscles appeared to influence the muscles' responsiveness to the fasting, since the highly glycolytic TFL was the most sensitive (particularly after 36 h of fasting), whereas the highly oxidative adductor longus and soleus muscles were unaffected by either fasting or insulin. In a second experiment, refeeding of fasted adult rats also had little effect on Ks, consistent with the low sensitivity to fasting shown by the first experiment. The parallel results in the two experiments confirmed that the low responsiveness to fasting and insulin infusion in these adult rats was not a result of failure to absorb in “fed” animals or insufficient levels of insulin during insulin infusions. In contrast, a third experiment showed that muscle protein synthesis in the gastrocnemius muscle from young adult (5-mo-old) female rats was significantly reduced after only 12 h of fasting.


2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.


1975 ◽  
Vol 26 (6) ◽  
pp. 1063
Author(s):  
LEA Symons ◽  
WO Jones

Incorporation of radioisotopically labelled L-leucine into skeletal muscle proteins was measured in vivo and in vitro, and into liver proteins in vivo in three groups of sheep: (1) infected by Trichostrongylus colubriformis, (2) uninfected, pair-fed with the infected animals, (3) uninfected, fed ad lib. Incorporation of [14C]L-leucine by an homogenate of wool follicles from infected and uninfected sheep was also measured. Incorporation of leucine by muscle, and hence muscle protein synthesis, was equally depressed in the anorexic infected sheep losing weight, and in pair-fed animals, whether measured in vivo or in vitro, or expressed in terms of either RNA or DNA. Incorporation into protein was elevated equally in vivo in the livers of the infected and pair-fed sheep when expressed in terms of content of tissue nitrogen, but not in terms of cither nucleic acid. Incorporation by the wool follicular homogenate was appreciably depressed by the infection and is consistent with the poor wool growth in nematode infections. These results show that the same depression of skeletal muscle and, possibly, elevation of liver protein synthesis occur in a ruminant as were reported earlier for laboratory monogastric animals with intestinal nematode infections. Pair-feeding uninfected animals in both this and the earlier experiments emphasized the importance of anorexia as a major cause of these effects on protein synthesis. The importance of these effects upon production is discussed briefly.


1989 ◽  
Vol 77 (6) ◽  
pp. 651-655 ◽  
Author(s):  
S. D. Heys ◽  
A. C. Norton ◽  
C. R. Dundas ◽  
O. Eremin ◽  
K. Ferguson ◽  
...  

1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 μg/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 μmol/100 g body weight) 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane.


Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.


1981 ◽  
Vol 241 (3) ◽  
pp. E221-E225 ◽  
Author(s):  
K. Taya ◽  
G. S. Greenwald

Thirty-day-old rats given a single subcutaneous injection of 5 IU pregnant mare serum gonadotropin (PMS) at 0900 h ovulated on the morning of day 33 (= estrus). However, the second ovulation did not occur until 9.4 days later. To determine the mechanism responsible for the delay in the second ovulation, in vivo and in vitro determinations of steroid and peptide hormones were compared between PMS-primed immature rats and adult cyclic rats. In PMS-primed rats, the corpora lutea (CL) produced progesterone for 2 days longer (until day 36) than the CL of the adult rat. Serum levels of 20 alpha-dihydroprogesterone, testosterone, and estradiol in PMS-primed rats were significantly lower than the corresponding values in adult rats. Serum LH was consistently lower in the PMS-primed rats. An increase in serum FSH occurred on days 36–37, which may be responsible for maturation of the follicles destined to ovulate at the second ovulation. On day 37, the nonluteal ovary of the PMS-primed rats also began to produce in vitro appreciable amounts of testosterone and estradiol. These findings suggest that the greater levels of prolactin and/or low levels of luteinizing hormone during estrus in PMS-primed rats may be responsible for the prolonged secretion of progesterone by the CL. This in turn inhibits follicular maturation, indirectly by lowering serum LH, which is reflected in reduced ability of the follicles in vitro to produce testosterone and estradiol until the CL regress.


1999 ◽  
Vol 18 (2) ◽  
pp. 106-110
Author(s):  
Livia Secondin ◽  
Stefano Maso ◽  
Andrea Trevisan

1 Nephrotoxic effects of 1,3-dichloropropene (cis and trans isomers mixture) was investigated in vitro by means of renal cortical slice model in male and female rats, including treatment with metabolism modifiers as an inducer of cytochrome P-450 1A class (β-naphtho-flavone), a reduced glutathione depleting (DL-buthio-nine-[S, R]-sulfoximine), an inhibitor of g-glutamyltransferase (AT-125) and inhibitor of cysteine conjugate β-lyase (aminooxiacetic acid).2 Dose-dependent decrease of p-aminohippurate uptake was observed in male renal cortical slices. Only the high doses (3.0 and 4.0×10-4M) caused a significant loss of organic anion uptake in females.3 β-Naphthoflavone and α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) partially, but significantly, reduced organic anion loss in males. In females, DL-buthionine-[S, R]-sulfoximine significantly increased in females but in males loss of organic anion accumulation caused by 1,3-dichloropropene. Aminooxyacetic acid did not ameliorate 1,3 D effects in vivo and in vitro in male rats. It appeared very toxic for female rats (all rats died) after in vivo injection.4 Sensitivity to nephrotoxicity induced by 1,3-dichlor-opropene in vitro was about double in male than female rats. Reduced glutathione conjugation appeared involved in nephrotoxicity induced in males but in females, probably by means of a chloropropylcysteinylglycine-conjugate formation; slight toxicity in females is likely related to oxidative metabolism.


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