RESUMO
Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.
Assuntos
Poluentes Atmosféricos/toxicidade , Dieta Hiperlipídica , Obesidade , Ozônio/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Comportamento Sedentário , Animais , Glicemia/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Feminino , Masculino , Gravidez , Ventilação Pulmonar/efeitos dos fármacos , Ratos , Ratos Long-Evans , Caracteres SexuaisRESUMO
The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity, which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22-day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 wk the rats ran 310 ± 16.3 km. Responses of SED and ACT rats to whole-body O3 (0, 0.25, 0.5, or 1.0 ppm; 5 h/day for 2 days) was assessed. Glucose tolerance testing (GTT) was performed following the first day of O3 ACT rats had less body fat and an improved glucose GTT. Ventilatory function (plethysmography) of SED and ACT groups was similarly impaired by O3 Bronchoalveolar lavage fluid (BALF) was collected after the second O3 exposure. SED and ACT rats were hyperglycemic following 1.0 ppm O3 GTT was impaired by O3 in both groups; however, ACT rats exhibited improved recovery to 0.25 and 1.0 ppm O3 BALF cell neutrophils and total cells were similarly increased in ACT and SED groups exposed to 1.0 ppm O3 O3-induced increase in eosinophils was exacerbated in SED rats. Chronic exercise from postweaning to adulthood improved some of the metabolic and pulmonary responses to O3 (GTT and eosinophils) but several other parameters were unaffected. The reduction in O3-induced rise in BALF eosinophils in ACT rats suggests a possible link between a SED lifestyle and incidence of asthma-related symptoms from O3.
Assuntos
Envelhecimento/fisiologia , Ozônio/farmacologia , Condicionamento Físico Animal , Desmame , Animais , Biomarcadores/sangue , Composição Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Suscetibilidade a Doenças , Feminino , Pletismografia , Ratos Long-Evans , Fatores de TempoRESUMO
Body fat serves as a storage compartment for lipophilic pollutants and affects the pharmacokinetics of many toxic chemicals. Understanding how body fat varies with gender, strain, and age may be essential for development of experimental models to study mechanisms of toxicity. Nuclear magnetic resonance (NMR)-based analysis serves as a noninvasive means of assessing proportions of fat, lean, and fluid in rodents over their lifetime. The aim of this study was to track changes in body composition of male and female Long-Evans (LE), Sprague-Dawley (SD), Fischer (F334), and Brown Norway (BN) rats from postweaning over a >2-yr period. Percent fat of preweaned LE and SD rats was markedly higher compared to the other strains. LE and SD strains displayed marked increases in body fat from weaning to 8 mo of age. Postweaned F344 male and females showed relatively low levels of percent fat; however, at 2 yr of age percent fat of females was equal to that of SD and LE in females. BN rats showed the highest levels of lean tissue and lowest levels of fat. Percent fat of the BN strain rose at the slowest rate as they aged. Percent fluid was consistently higher in males for all strains. Females tended to have higher percent fat than males in LE, SD, and F344 strains. Assessing changes in body fat as well as lean and fluid of various strains of male and female rats over their lifetime may prove useful in many research endeavors, including pharmacokinetics of lipophilic toxicants, mechanisms underlying obesity, and metabolic disorders.
Assuntos
Composição Corporal/genética , Ratos/fisiologia , Fatores Etários , Animais , Feminino , Estudos Longitudinais , Masculino , Ratos/genética , Ratos Endogâmicos BN/genética , Ratos Endogâmicos BN/fisiologia , Ratos Endogâmicos F344/genética , Ratos Endogâmicos F344/fisiologia , Ratos Long-Evans/genética , Ratos Long-Evans/fisiologia , Ratos Sprague-Dawley/genética , Ratos Sprague-Dawley/fisiologia , Fatores Sexuais , Especificidade da EspécieRESUMO
Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (O3); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and then exposed to O3 (acute - air or 0.8 ppm O3 for 5 h, or subacute - air or 0.8 ppm O3 for 5 h/d 1 d/week for 4 weeks). Body composition was measured non-invasively using NMR. Ventilatory parameters and exploratory behavior were measured after the third week of subacute exposure. Bronchoalveolar lavage fluid (BALF) and blood chemistry data were collected 18 h after acute O3 and 18 h after the fourth week of subacute O3. The diets led to increased body fat in male but not female rats. O3-induced changes in ventilatory function were either unaffected or improved with the fructose and fat diets. O3-induced reduction in exploratory behavior was attenuated with fructose and fat diets in males and partially in females. O3 led to a significant decrease in body fat of males fed control diet but not the fructose or fat diet. O3 led to significant increases in BALF eosinophils, increase in albumin, and reductions in macrophages. Female rats appeared to be more affected than males to O3 regardless of diet. Overall, treatment with high-fructose and high-fat diets attenuated some O3 induced effects on pulmonary function, behavior, and metabolism. Exacerbation of toxicity was observed less frequently.
Assuntos
Poluentes Atmosféricos/toxicidade , Dieta Hiperlipídica , Frutose/farmacologia , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Albuminas/metabolismo , Animais , Contagem de Células Sanguíneas , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Ingestão de Alimentos/efeitos dos fármacos , Eosinófilos/citologia , Feminino , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Macrófagos/citologia , Masculino , Atividade Motora/efeitos dos fármacos , Ventilação Pulmonar/efeitos dos fármacos , RatosRESUMO
Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65 days compared to sedentary (SED) housing in five female rat strains: Sprague-Dawley (SD), Long-Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise.
Assuntos
Tecido Adiposo/metabolismo , Metabolismo Basal/genética , Ingestão de Alimentos/genética , Atividade Motora/genética , Ventilação Pulmonar/genética , Redução de Peso/genética , Animais , Composição Corporal , Ingestão de Líquidos , Comportamento Exploratório , Feminino , Ratos , Ratos EndogâmicosRESUMO
NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improved longevity with caloric restriction (CR) in rodents. Little is known regarding effects of CR in genetically lean versus obese strains. Long-Evans (LE) and Brown Norway (BN) rats make an ideal comparison for a CR study because the percentage body fat of young adult LE rats is double that of BN rats. Male LE and BN rats were either fed ad libitum (AL) or were calorically restricted to 80 or 90% of their AL weight. The percentages of fat, lean and fluid mass were measured non-invasively at 2- to 4-week intervals. Metabolic rate and respiratory quotient were measured after 3, 6, 9 and 12 months of CR. Overall health was scored monthly. The percentage of fat of the LE strain decreased with CR, whereas the percentage of fat of the BN strain remained above the AL group for several months. The percentage of lean mass increased above the AL for both strains subjected to CR. The percentage of fluid was unaffected by CR. The average metabolic rate over 22 h of the BN rats subjected to CR was reduced, whereas that of LE rats was increased slightly above the AL group. The respiratory quotient of BN rats was decreased with CR. Overall health of the CR LE group was significantly improved compared with that of the AL group, whereas health of the CR BN rats was impaired compared with the AL group. Overall, the lean BN and obese LE strains differ markedly in fat utilization and metabolic response to prolonged CR. There appears to be little benefit of CR in the lean strain.
Assuntos
Composição Corporal , Peso Corporal , Restrição Calórica , Obesidade/metabolismo , Animais , Metabolismo Basal , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Long-EvansRESUMO
AIM: Few investigators have considered the possibility that skeletal muscles might contain thermosensitive elements capable of modifying thermoeffector responses. In this experiment, the temporal relationships between dynamic changes in deep-body and intramuscular temperatures and eccrine sweat secretion were explored during rhythmical and reproducible variations in heat production. METHODS: Eight subjects performed semi-recumbent cycling (25 °C) at a constant load to first establish whole-body thermal and sudomotor steady states (35 min), followed by a 24-min block of sinusoidal workload variations (three, 8-min periods) and then returning to steady-state cycling (20 min). Individual oesophageal, mean skin and intramuscular (vastus lateralis) temperatures were independently cross-correlated with simultaneously measured forehead sweat rates to evaluate the possible thermal modulation of sudomotor activity. RESULTS: Both intramuscular and oesophageal temperatures showed strong correlations with sinusoidal variations in sweating with respective maximal cross-correlation coefficients of 0.807 (±0.044) and 0.845 (±0.035), but these were not different (P = 0.40). However, the phase delay between intramuscular temperature changes and sweat secretion was significantly shorter than the delay between oesophageal temperature and sweating [25.6 s (±12.6) vs. 46.9 s (±11.3); P = 0.03]. CONCLUSION: The temporal coupling of eccrine sweating to intramuscular temperature, combined with a shorter phase delay, was consistent with the presence of thermosensitive elements within skeletal muscles that appear to participate in the modulation of thermal sweating.
Assuntos
Regulação da Temperatura Corporal/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Sudorese/fisiologia , Adulto , Temperatura Corporal/fisiologia , Glândulas Écrinas/fisiologia , Retroalimentação Fisiológica , Humanos , MasculinoRESUMO
Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O3) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O3 (6 h/day of 1 ppm O3 for 2 consecutive days/week for 13 weeks). Acute O3 initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O3. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O3 exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O3, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O3 exposure. MA was elevated in adults but not senescent rats during recovery from O3. Overall, acute effects of O3, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O3 in senescent rats may explain the relatively heightened physiological response to O3 in younger rats.
Assuntos
Envelhecimento , Poluentes Atmosféricos/toxicidade , Bradicardia/induzido quimicamente , Hipotermia/induzido quimicamente , Exposição por Inalação/efeitos adversos , Síndromes Neurotóxicas/fisiopatologia , Ozônio/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Oxidantes Fotoquímicos/toxicidade , Ratos Endogâmicos BN , Índice de Gravidade de Doença , Taquifilaxia , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , ToxicocinéticaRESUMO
Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2>1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation.
Assuntos
Intolerância à Glucose/patologia , Doenças Metabólicas/patologia , Ozônio/toxicidade , Adiponectina/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Fatores Etários , Animais , Biomarcadores/metabolismo , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Leptina/sangue , Lipoproteínas HDL/sangue , Lipoproteínas IDL/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/induzido quimicamente , Osteopontina/sangue , Fosforilação , Ratos , Ratos Endogâmicos BN , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Triglicerídeos/sangue , alfa-Macroglobulinas/metabolismoRESUMO
Ozone (O3) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O3; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O3 exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O3 for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O3 exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O3 7 d after exposure in both age groups was observed. O3 had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O3 affected 6/58; 2/58 showed an age-O3 interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O3 than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.
Assuntos
Comportamento Animal/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Adiponectina/metabolismo , Fatores Etários , Envelhecimento , Animais , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Suscetibilidade a Doenças , Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Insulina/metabolismo , Leptina/metabolismo , Lipocalinas/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos BN , Testes de Função RespiratóriaRESUMO
Recent research on the acute effects of volatile organic compounds suggests that extrapolation from short (â¼1 h) to long durations (up to 4 h) may be improved by using estimates of brain toluene concentration (Br[Tol]) instead of cumulative inhaled dose (C × t) as a metric of dose. This study compared predictions of these two dose metrics on the acute behavioral effects of inhaled toluene in rats during exposures up to 24 h in duration. We first evaluated estimates of Br[Tol] with a physiologically based toxicokinetic (PBTK) model for rats intermittently performing an operant task while inhaling toluene for up to 24 h. Exposure longer than 6 h induced P450-mediated metabolism of toluene. Adjusting the corresponding parameters of the PBTK model improved agreement between estimated and observed values of Br[Tol] in the 24-h exposure scenario. Rats were trained to perform a visual signal detection task and were then tested while inhaling toluene (0, 1125, and 1450 ppm for 24 h and 1660 ppm for 21 h). Tests occurred at times yielding equivalent C × t products but different estimates of Br[Tol], and also at 1 and 6 h afterexposure. Effects of toluene were better predicted by Br[Tol] than by C × t. However, even using Br[Tol] as the dose metric (after accounting for metabolic induction), acute dose-effect functions during 24-h exposures were shifted to the right relative to 1-h exposures, indicating that a dynamic behavioral tolerance also developed during prolonged exposure to toluene.
Assuntos
Comportamento Animal/efeitos dos fármacos , Solventes/toxicidade , Tolueno/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Bases de Dados de Proteínas , Relação Dose-Resposta a Droga , Exposição por Inalação , Aprendizagem/efeitos dos fármacos , Masculino , Modelos Biológicos , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Detecção de Sinal Psicológico/efeitos dos fármacos , Solventes/farmacocinética , Fatores de Tempo , Tolueno/farmacocinética , Testes de Toxicidade AgudaRESUMO
Time of day of exposure is rarely considered in the study of insecticide toxicology. It would be expected that the circadian temperature rhythm (CTR) as well as the circadian rhythms of other physiological processes would affect the efficacy of anticholinesterase (antiChE) insecticides. The ability of antiChE insecticides to alter core temperature (T(c)) could be affected by time of exposure in relation to the CTR. To this end, we assessed time of exposure on the efficacy of the antiChE insecticides chlorpyrifos (CHP) and carbaryl (CAR) to alter T(c) in the rat. T(c) and motor activity (MA) were monitored by radiotelemetry. Rats were dosed orally with 0, 30, and 50 mg/kg CHP or 0, 25 and 75 mg/kg CAR at 09:00 and 15:00 h. Both insecticides caused an acute decrease followed by a delayed increase in T(c) by 24-48 h post-exposure. The temperature index (TI) (area under curve of DeltaT(c) with time) was significantly greater when CHP was given at 15:00 h as compared with 09:00 h. The maximum decrease in T(c) was similar for morning and afternoon CHP. The TI following CAR was similar for morning and afternoon exposure. CHP suppressed the 24 h MA equally when given in the morning and afternoon. CAR was more effective in reducing MA when given in the morning as compared with the afternoon. The T(c) increase measured 24 h after dosing was greater when CHP was given in the morning. Overall, time of day affected the thermoregulatory toxicity of CHP but not CAR. Another experiment showed that the hypothermic efficacy of oxotremorine, a muscarinic agonist, was greater when injected at 09:00 h as compared with 15:00 h. Hence, cholinergic stimulation is probably not the only mechanism to explain the effects of the chronotoxicogical effects of some antiChE insecticides.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Carbaril/toxicidade , Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Ritmo Circadiano/efeitos dos fármacos , Inseticidas/toxicidade , Animais , Relação Dose-Resposta a Droga , Privação de Alimentos/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Oxotremorina/farmacologia , Ratos , Ratos Long-Evans , TelemetriaRESUMO
Thermal dysthesia, characterized by a painful sensation of warm and cool surfaces, is one of many ailments in humans exposed to various marine algal toxins such as brevetoxin (PbTx). There is no animal model to study thermal dysthesia and little is known of the mechanism of action. There is also little known on the acute and delayed thermoregulatory effects of PbTx. In this study, we developed a behavioral system to assess the possible development of thermal dysthesia in mice exposed to PbTx. Female mice were implanted with radiotransmitters to monitor core temperature (Tc) and motor activity (MA). In one experiment, mice were dosed with the control vehicle or 180 microg/kg PbTx and placed on a floor temperature gradient to measure the selected foot temperature (SFT) while air temperature was kept constant. PbTx-treated mice underwent a 10 degrees C reduction in SFT concomitant with a 3 degrees C reduction in Tc within 30 min after exposure. In another study, Tc and MA were monitored in mice maintained in their home cages after dosing with 180 microg/kg PbTx. Tc but not MA increased for 2-5 days after exposure. SFT was unaffected by PbTx when tested 1-12 days after exposure. However, PbTx-treated mice underwent an increase in Tc when placed in the temperature gradient for up to 12 days after exposure. This suggests that PbTx augments the stress-induced hyperthermia from being placed in a novel environment. Overall, acute PbTx exposure leads to a regulated reduction in Tc as characterized by a preference for cooler SFTs and a reduced Tc. Thermal dysthesia was not apparent, but the exaggerated hyperthermic response with a normal SFT in the temperature gradient may suggest an altered processing of thermal stimuli in mice treated with PbTx.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Toxinas Marinhas/farmacologia , Neurotoxinas/farmacologia , Oxocinas , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Camundongos , TelemetriaRESUMO
Reducing body temperature of rodents has been found to improve their survival to ischaemia, hypoxia, chemical toxicants, and many other types of insults. Larger species, including humans, may also benefit from a lower body temperature when recovering from CNS ischaemia and other traumatic insults. Rodents subjected to these insults undergo a regulated hypothermic response (that is, decrease in set point temperature) characterised by preference for cooler ambient temperatures, peripheral vasodilatation, and reduced metabolic rate. However, forced hypothermia (that is, body temperature forced below set point) is the only method used in the study and treatment of human pathological insults. The therapeutic efficacy of the hypothermic treatment is likely to be influenced by the nature of the reduction in body temperature (that is, forced versus regulated). Homeostatic mechanisms counter forced reductions in body temperature resulting in physiological stress and decreased efficacy of the hypothermic treatment. On the other hand, regulated hypothermia would seem to be the best means of achieving a therapeutic benefit because thermal homeostatic systems mediate a controlled reduction in core temperature.
Assuntos
Lesões Encefálicas/terapia , Isquemia Encefálica/terapia , Serviços Médicos de Emergência , Hipotermia Induzida , Intoxicação/terapia , Animais , Regulação da Temperatura Corporal/fisiologia , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/fisiopatologia , Homeostase/fisiologia , Humanos , Intoxicação/fisiopatologia , Roedores , Especificidade da Espécie , Estresse Fisiológico/fisiopatologiaRESUMO
Body (core) temperature (T(c)) directly affects all biological processes, including sensitivity to toxic chemicals, development, aging, and drug metabolism. To understand how T(c) affects these processes it is necessary to alter T(c) independently of other physiological processes. The purpose of this study was to determine whether selective breeding techniques can be used to develop lines of rats with hyperthermic and hypothermic T(c)'s. T(c) and motor activity of 24 female and 23 male rats (parental line) of the NIH heterogenous stock were monitored by telemetry for 96h at a T(a) of 22 degrees C. The mean 24h T(c) of the male and female rats was 37.3 degrees C with a range of 37-38.2 degrees C. T(c) was not correlated with motor activity or body weight. Pairs with the lowest and highest T(c)'s were selected for breeding. The F1 generation consisted of 10 offspring from the hyperthermic group and 20 from the hypothermic group. They were implanted with transmitters at 60d of age. T(c) of rats derived from the hyperthermic parental line had a significantly warmer T(c) than the rats derived from the hypothermic parental line. Motor activity was significantly higher in the hyperthermic F1 males and hypothermic F1 females. Breeding of hyperthermic and hypothermic rats has shown that adult offspring of the fourth generation maintain significantly different core temperatures but have similar patterns of motor activity. The results demonstrate that T(c) is heritable and that it should be feasible to develop lines of rats that regulate T(c) above or below normal.
RESUMO
Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing cholinergic stimulation in the central nervous system (CNS). Cholinergic systems are crucial in electroencephalogram (EEG) generation and regulation of behavior; however, little is known about how OP exposure affects the EEG and behavioral states. We recorded EEG, core temperature and motor activity before and after exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted with telemetric transmitters. The recording and reference electrodes were placed in the occipital and frontal bones, respectively. The animals received CHP, 25 mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant increase in delta (0.1-3.5 Hz), slow theta (4-6.5 Hz), gamma 2 (35.5-50 Hz), reduction in fast theta (7-8.5 Hz), alpha/sigma (9-14 Hz), beta 1 (14.5-24 Hz), beta 2 (24.5-30 Hz) and gamma 1 (30.5-35 Hz) powers, slowing of peak frequencies in 1-9 Hz range, hypothermia and decrease in motor activity. The drop in 7-14 Hz was associated with cholinergic suppression of sleep spindles. Changes in behavioral state were characterized by dramatic diminution of sleep postures and exploring activity and prolongation of quiet waking. There was recovery in all bands in spite of continued inhibition of AChE activity [44,45] in rats exposed to CHP. OX-induced EEG and behavioral alterations were similar to CHP except there was no increase in delta and the onset and recovery were more rapid. We did not find a correlation between the EEG and core temperature alterations. Overall, changes in EEG (except in delta band) and behavior following CHP were attributable to muscarinic stimulation. Cortical arousal together with increased quiet waking and decreased sleep after CHP occurred independently from inhibition of motor activity and lowering of core temperature.
Assuntos
Comportamento Animal/efeitos dos fármacos , Clorpirifos/administração & dosagem , Eletroencefalografia/efeitos dos fármacos , Oxotremorina/administração & dosagem , Administração Oral , Animais , Temperatura Corporal/efeitos dos fármacos , Inibidores da Colinesterase/administração & dosagem , Feminino , Injeções Subcutâneas , Monitorização Ambulatorial/instrumentação , Atividade Motora/efeitos dos fármacos , Agonistas Muscarínicos/administração & dosagem , Postura , Ratos , Ratos Sprague-Dawley , Processamento de Sinais Assistido por Computador , Sono/efeitos dos fármacos , Sono/fisiologia , Telemetria , Vigília/efeitos dos fármacos , Vigília/fisiologiaRESUMO
Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set point) as well as the response to infectious fever Chlorpyrifos (CHP), an organophosphate insecticide, also affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. This study examined whether chronic exercise training in the rat alters the thermoregulatory response to CHP. Core temperature and motor activity were monitored by radiotelemetry in female Sprague-Dawley rats housed individually at an ambient temperature of 22 degrees C. The rats were either given continuous access to running wheels or housed in standard cages without wheels. The exercise group ran predominately at night. After 8 weeks, the rats were gavaged with corn oil or 15 mg/kg CHP. CHP induced a transient hypothermic response followed by a delayed fever, beginning 1 day after exposure. Relative to controls, T7 decreases were not significantly different between the exercise (1.6 degrees C) group and the sedentary (0.5 degrees C) group given CHP. The sedentary and exercise group administered CHP developed a fever the day after CHP treatment. The fever response was greater in the sedentary group and persisted for approximately 3 days post-injection. Fever of the exercise group persisted for just one-half of 1 day after CHP. It is well known that chronic exercise training improves aerobic capacity; however, trained rats were not protected from the hypothermic effects of CHP. Training did ameliorate the febrile effects of CHP. Thus, exercise training may afford protection to the toxic effects of organophosphate insecticides.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Condicionamento Físico Animal , Animais , Colinesterases/sangue , Feminino , Ratos , Ratos Sprague-DawleyRESUMO
How borderline impairment of thyroid function can affect thermoregulation is an important issue because of the antithyroidal properties of a many environmental toxicants. This study compared the efficacy of heat and cold stress to identify thermoregulatory deficits in rats subjected to borderline and overt hypothyroidism via subchronic exposure to propylthiouracil (PTU). After 3 wk of exposure to PTU in the drinking water (0, 2.5, 5, 10, and 25 mg/l), rats were subjected to a heat stress challenge (34 degrees C for 2.5 h). After one more week of PTU treatment, the same rats were subjected to a cold stress challenge (7 degrees C for 2.5 h). Core temperature (T(c)) was monitored by radiotelemetry. Baseline T(c) during the light phase was reduced by treatment with 25 mg/l PTU. The rate of rise and overall increase in T(c) during heat stress was attenuated by PTU doses of 10 and 25 mg/l. Cold stress resulted in a 1.0 degrees C increase in T(c) regardless of PTU treatment. The rate of rise in T(c) during the cold stress challenge was similar in all PTU treatment groups. There was a dose-related decrease in serum thyroxine (T(4)) at PTU doses >/=5 mg/l. Serum triiodothyronine (T(3)) was reduced at PTU doses of 5 and 25 mg/l. Serum thyroid-stimulating hormone (TSH) was marginally elevated by PTU treatment. Overall, heat stress was more effective than cold stress for detecting a thermoregulatory deficit in borderline (i.e., 10 mg/l PTU) and overtly hypothyroid rats (i.e., 25 mg/l PTU). A significant thermoregulatory deficit is manifested with a 78% decrease in serum T(4). A thermoregulatory deficit is more correlated with a reduction in serum T(4) compared with T(3). Serum levels of TSH are unrelated to thermoregulatory response to heat and cold stress.
Assuntos
Aclimatação/fisiologia , Regulação da Temperatura Corporal/fisiologia , Hipotireoidismo/fisiopatologia , Ciclos de Atividade , Animais , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Temperatura Baixa , Temperatura Alta , Hipotireoidismo/induzido quimicamente , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Propiltiouracila/farmacologia , Ratos , Ratos Long-Evans , Estresse Fisiológico , Tri-Iodotironina/sangueRESUMO
Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25 degrees. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t)) concomitant with a 0.5 degrees reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS.