Marked depression of radiation-induced emesis in frogs following prior exposure to a brief dose of X-rays

2002 ◽  
Vol 80 (8) ◽  
pp. 828-832 ◽  
Author(s):  
Yukihisa Miyachi ◽  
Takahisa Koike ◽  
Kenzo Muroi ◽  
Tomoko Kanao ◽  
Taro Kawamoto ◽  
...  
Keyword(s):  
Low Dose ◽  
Lethal Dose ◽  
Prior Exposure ◽  
Whole Body ◽  
High Dose ◽  
X Rays ◽  
Sham Control ◽  
Toxic Dose ◽  
Acute Emesis ◽  
Radiation Induced

Acute emesis response to harmful doses of X-rays on frogs (Rana porosa porosa) was examined. Results showed that the number of radioemesis events following exposure to 0.85 Gy was slightly higher than in the sham control animals. The increase in emesis action became more pronounced when the total dose of radiation was raised to 2.5 Gy. Only 1 frog out of a total of 12 did not show vomiting following radiation, while no response was observed in sham control animals. Note that animals in which the low dose rate of radiation was applied to whole body did not display any changes in the emesis response relative to control animals. The present studies, and those by others, showed that a brief dose of X-rays prior to a second exposure to a sub-lethal dose might induce a tolerance to radiation. An additional experiment was conducted to examine whether a small conditioning dose could induce a depression of radioemesis (tolerance) following an exposure to high dose X-ray. With prior exposure to 0.3 Gy, only 1 frog out of a total of 5 frogs vomited as a result of radiation exposure. Suppression of the emetic response became significant when the pre-radiation dose was decreased to 0.1 Gy. On the contrary, increasing the small conditioning dose to 0.5 Gy resulted in a remarkable rise of radiation-induced emesis. This results indicate that exposure to the smaller dose of X-rays elicits a tolerance effect to toxic dose level of radiation.Key words: emesis, hormesis, low-dose X-rays, resistance, frog.

scholarly journals Optimal LDR to Protect the Kidney From Diabetes: Whole-Body Exposure to 25 mGy X-rays Weekly for 8 Weeks Efficiently Attenuates Renal Damage in Diabetic Mice

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878984 ◽  
Author(s):  
Jie Cheng ◽  
Fengsheng Li ◽  
Guanjun Wang ◽  
Weiying Guo ◽  
Shan Huang ◽  
...  
Keyword(s):  
Low Dose ◽  
Collagen Iv ◽  
Whole Body ◽  
Detectable Effect ◽  
X Rays ◽  
Diabetic Mice ◽  
Low Dose Radiation ◽  
Functional Changes ◽  
Renal Expression

To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.

A study of the effect of X-rays on the electrical properties of mammalian nerve and muscle

1963 ◽  
Vol 157 (969) ◽  
pp. 536-561 ◽  
Keyword(s):  
Dose Rate ◽  
Action Potentials ◽  
Time Course ◽  
Low Dose ◽  
High Dose ◽  
X Rays ◽  
Low Dose Rate ◽  
End Plate ◽  
Small Doses ◽  
Motor End Plate

Resting potentials, action potentials, and miniature end-plate potentials have been re­corded from isolated phrenic-diaphragm preparations of the rat during and after irradiation with X-rays. Relatively small doses of a few thousand roentgens have no obvious effect on the preparation for many hours but larger doses, of the order of 70 to 150 kr irreversibly block neuromuscular transmission. The block is not accompanied by any change in the size of action potentials, resting potentials, membrane constants or miniature potentials recorded in the muscle with intracellular electrodes, or in the size of action potentials recorded in the nerve. Records made at the motor end-plate show that the cause of the block is a ‘pre-synaptic ’ failure of impulse propagation in the intramuscular part of the nerve. The time course of the failure depends largely on the rate at which X-rays are delivered to the pre­paration: at a high dose-rate (70kr/min) the block develops rapidly and is accompanied by an increase in the frequency of miniature potentials; at a low dose-rate (7 kr/min) larger doses are required, the latency is longer and the miniature potentials continue at a normal frequency. The sequence in which different parts of the muscle become blocked, the abrupt nature of the failure at an individual motor end-plate, and the increase in frequency of the miniature potentials together suggest that the action of X-rays is to block conduction in the nerve near its terminals, possibly by depolarizing points where the axons branch and the safety factor for the propagation of impulses is low. The results reported in this paper do not support the hypotheses that small doses of X-rays at a high or a low dose-rate lead to an initial 'enhancement' of function or that they produce immediate and reversible changes in the permeability of excitable membranes to ions.

scholarly journals Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events

2017 ◽  
Vol 59 (suppl_2) ◽  
pp. ii11-ii17 ◽  
Author(s):  
Haruki Nagashima ◽  
Kumiko Shiraishi ◽  
Saori Ohkawa ◽  
Yuki Sakamoto ◽  
Kenshi Komatsu ◽  
...  
Keyword(s):  
Low Dose ◽  
Somatic Mutations ◽  
X Rays ◽  
Radiation Induced

Proteomics ofS-(1, 2-dichlorovinyl)-l-cysteine-induced acute renal failure and autoprotection in mice

2007 ◽  
Vol 293 (4) ◽  
pp. F994-F1006 ◽  
Author(s):  
Midhun C. Korrapati ◽  
Jaya Chilakapati ◽  
Frank A. Witzmann ◽  
Chundury Rao ◽  
Edward A. Lock ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Low Dose ◽  
Lethal Dose ◽  
High Dose ◽  
Two Dimensional Gel Electrophoresis ◽  
Α Subunit ◽  
Treatment Groups ◽  
Liquid Chromatography Tandem Mass

Previous studies (Vaidya VS, Shankar K, Lock EA, Bucci TJ, Mehendale HM. Toxicol Sci 74: 215–227, 2003; Korrapati MC, Lock EA, Mehendale HM. Am J Physiol Renal Physiol 289: F175–F185, 2005; Korrapati MC, Chilakapati J, Lock EA, Latendresse JR, Warbritton A, Mehendale HM. Am J Physiol Renal Physiol 291: F439–F455, 2006) demonstrated that renal repair stimulated by a low dose of S-(1,2-dichlorovinyl)l-cysteine (DCVC; 15 mg/kg ip) 72 h before administration of a normally lethal dose (75 mg/kg ip) protects mice from acute renal failure (ARF) and death (autoprotection). The present study identified the proteins indicative of DCVC-induced ARF and autoprotection in male Swiss Webster mice. Renal dysfunction and injury were assessed by plasma creatinine and histopathology, respectively. Whole-kidney homogenates were run on two-dimensional gel electrophoresis gels, and the expression of 18 common proteins was maximally changed (≥10-fold) in all the treatment groups and they were conclusively identified by liquid chromatography tandem mass spectrometry. These proteins were mildly downregulated after low dose alone and in autoprotected mice in contrast to severe downregulation with high dose alone. Glucose-regulated protein 75 and proteasome α-subunit type 1 were further investigated by immunohistochemistry for their localization in the kidneys of all the groups. These proteins were substantially higher in the proximal convoluted tubular epithelial cells in the low-dose and autoprotected groups compared with high-dose alone group. Proteins involved in energetics were downregulated in all the three groups of mice, leading to a compromise in cellular energy. However, energy is recovered completely in low-dose and autoprotected mice. This study provides the first report on proteomics of DCVC-induced ARF and autoprotection in mice and reflects the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicological paradigms.

Tolerance of rats to a cold environment during multiple exposures to a low dose of x rays

1961 ◽  
Vol 200 (5) ◽  
pp. 1039-1042 ◽  
Author(s):  
Bernard D. Newsom ◽  
Donald J. Kimeldorf
Keyword(s):  
Cold Exposure ◽  
Low Dose ◽  
Lethal Dose ◽  
Dose Fractionation ◽  
Cold Environment ◽  
X Rays ◽  
Time Intervals ◽  
Multiple Exposures ◽  
X Irradiation ◽  
Food Consumed

A lethal dose of X irradiation can be made sublethal by the fractionation of a dose into a series of smaller doses separated by adequate time intervals. The results reported here demonstrate how an environmental stress, such as cold, may affect this mitigating action of dose fractionation. Rats were maintained at 6 C while receiving a total dose of 600 r in one or eight exposures with various intervals between exposures. A greater interval was required between radiation exposures at 6 C than at 23 C to reduce the lethal response following irradiation. From the results of the food consumption measurements, it appears that cold exposure emphasizes the consequence of the reduced food intake which follows daily doses of 75 r in the rat. The irradiated rat was able to increase the amount of food consumed during cold exposure; however, the increase was not sufficient for adaptation. The lowered consumption which followed eight daily 75-r exposures was sufficient to cause death in pair-fed rats maintained at 6 C, but not at 23 C.

Left ventricular function during lethal and sublethal endotoxemia in swine

1986 ◽  
Vol 251 (2) ◽  
pp. H364-H373 ◽  
Author(s):  
R. D. Goldfarb ◽  
L. M. Nightingale ◽  
P. Kish ◽  
P. B. Weber ◽  
D. J. Loegering
Keyword(s):  
Low Dose ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Lethal Dose ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
High Dose ◽  
Adrenergic Stimulation ◽  
And Function

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

Molecular mechanisms of enhanced renal cell division in protection against S-1,2-dichlorovinyl-l-cysteine-induced acute renal failure and death

2005 ◽  
Vol 289 (1) ◽  
pp. F175-F185 ◽  
Author(s):  
Midhun C. Korrapati ◽  
Edward A. Lock ◽  
Harihara M. Mehendale
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Cell Division ◽  
Cyclin D1 ◽  
Renal Cell ◽  
Low Dose ◽  
Lethal Dose ◽  
S Phase ◽  
High Dose ◽  
Priming Dose

Sustained activation of ERK 1/2 by a low dose (15 mg/kg ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) 72 h before administration of a lethal dose of DCVC (75 mg/kg ip) enhances renal cell division and protects mice against acute renal failure (ARF) and death (autoprotection). The objective of this study was to determine correlation among extent of S-phase DNA synthesis, activation of transcription factors, expression of G1/S cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors downstream of ERK 1/2 following DCVC-induced ARF in autoprotection. Administration of the lethal dose alone caused a general downregulation or an unsustainable increase, in transcriptional and posttranscriptional events thereby preventing G1-S transition of renal cell cycle. Phosphorylation of IκBα was inhibited resulting in limited nuclear translocation of NF-κB. However, cyclin D1 expression was high probably due to transcriptional cooperation of AP-1. Cyclin D1/cyclin-dependent kinase 4 (cdk4)-cdk6 system-mediated phosphorylation of retinoblastoma protein was downregulated due to overexpression of p16 at 24 h after exposure to the lethal dose alone. Inhibition of S-phase stimulation was confirmed by proliferating cell nuclear antigen assay (PCNA). This inhibitory response was prevented if the lethal dose was administered 72 h after the low priming dose of DCVC due to promitogenic effect of the low dose. NF-κB-DNA binding is not limited if mice were pretreated with the priming dose. Cyclin D1/cdk4-cdk6 expression stimulated by the priming dose of DCVC was unaltered even after the lethal dose in the autoprotected group, explaining higher phosphorylated-pRB and S-phase stimulation found in this group. These results were corroborated with PCNA immunohistochemistry. These findings suggest that the priming dose relieves the block on compensatory tissue repair by upregulation of promitogenic mechanisms, normally blocked by the high dose when administered without the prior priming dose.

scholarly journals Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans

2009 ◽  
Vol 297 (3) ◽  
pp. E767-E773 ◽  
Author(s):  
Susan A. Phillips ◽  
Jacqueline Kung ◽  
Theodore P. Ciaraldi ◽  
Charles Choe ◽  
Louis Christiansen ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Low Dose ◽  
Whole Body ◽  
Serum Adiponectin ◽  
High Dose ◽  
Hmw Adiponectin ◽  
Dose Combination ◽  
Cell Expression ◽  
The Impact

Adiponectin, an insulin-sensitizing factor secreted from adipose tissue, is decreased in individuals with type 2 diabetes (T2D) and increased in response to thiazolidinedione (TZD) therapy. Changes in its secretion and assembly into higher-order forms affect insulin sensitivity. To determine the relative potency of TZDs on intra-adipocyte multimerization and secretion of adiponectin, we assessed the impact of in vivo low- or high-dose rosiglitazone treatment alone or combined with metformin in subjects with T2D. T2D subjects received high-dose rosiglitazone (8 mg/day), high-dose metformin (2,000 mg/day), or low-dose combination rosiglitazone-metformin therapy (4 mg + 1,000 mg/day) for 4 mo. All subjects were then switched to high-dose rosiglitazone-metformin combination therapy (8 mg + 2,000 mg/day) for another 4 mo. Low-dose rosiglitazone increased serum adiponectin, whereas the high dose increased both adipocyte content and serum adiponectin levels. TZDs selectively increased the percentage of circulating adiponectin in the potent, high-molecular-weight (HMW) form. No TZD effects were evident on multimer distribution in the cell. Expression of the chaperone protein ERp44, which retains adiponectin within the cell, was decreased by TZD treatment. No changes occurred in Ero1-Lα expression. Metformin had no effect on any of these measures. Increases in adiponectin correlated with improvements in insulin sensitivity. In vivo, TZDs have apparent dose-dependent effects on cellular and secreted adiponectin. TZD-mediated improvements in whole body insulin sensitivity are associated with increases in circulating but not cellular levels of the HMW adiponectin multimer. Finally, TZDs promote the selective secretion of HMW adiponectin, potentially, in part, through decreasing the expression of the adiponectin-retaining protein ERp44.

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