Dose- and sex-related carcinogenesis by N-bis(2-hydroxypropyl)nitrosamine in Wistar rats

An initiation-promotion medium-term bioassay for detection of chemical carcinogens, developed in the male F344 rat, uses 0.1% N-bis(2-hydroxypropyl)nitrosamine (DHPN) among five genotoxic chemicals for the initiation of carcinogenesis in multiple organs. To establish this bioassay in the Wistar strain, the effects of two dose levels of DHPN were evaluated on the main DHPN rat target organs: lung, thyroid gland, kidneys and liver. Four groups of male and female animals were studied: Control--untreated group; Multi-organ initiated group (also referred to as DMBDD, based on the initials of the five initiators)-treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), N-butyl-N-(4-hydroxy butyl)nitrosamine (BBN, drinking water), N, N'-dimethylhydrazine (DMH, s.c.) and DHPN (drinking water) for 4 weeks; a third group treated with 0.1% DHPN in drinking water for 2 weeks and the last group treated with 0.2% DHPN in drinking water for 4 weeks. The animals were sacrificed after 30 weeks. DHPN at 0.2% induced preneoplasia in the liver and kidneys of rats of both sexes, the number and area of the putative preneoplastic liver glutathione S-transferase-positive hepatocyte foci being significantly increased in these animals. It also induced benign and malignant tumors in female and in male rats. However, there was no relationship between the increased incidence of preneoplastic lesions and tumor development in the 0.2% DHPN-exposed groups of both sexes. DHPN at 0.1% induced only a few preneoplastic lesions in the liver and kidney and no tumors in both male and female rats. A clear dose and sex-related carcinogenic activity of DHPN was registered, although Wistar rats of both sexes showed a relative resistance to the carcinogenic activity of this compound.

Anthropometrical parameters and markers of obesity in rats

The present study was undertaken to determine anthropometrical parameters in male adult Wistar rats. We tested the hypothesis that the anthropometrical index may identify obesity and may predict its adverse effects on lipid profile and oxidative stress in rats. Two experimental protocols were performed. in the first experiment, 50 male Wistar rats, 21 days old and fed a control chow were studied up to 150 days of age. in the second experiment, male Wistar rats, 60 days old, were divided into three groups (n = 8): control (C) given free access to a control chow; (S) receiving the control chow and drinking 30% sucrose ad libitum and (HQ fed a high-carbohydrate diet ad libitum. The first experiment showed that food consumption, energy intake and body weight increased with increasing age, while specific rate of body mass gain was significantly decreased. There were no significant differences in body length and thoracic circumference of rats from 60 days of age. The abdominal circumference (AC) and body mass index (BMI) significantly increased with enhancing age in rats up to 90 days of age and remained constant thereafter. In the second experiment, after 30 days of dietary treatment, the final body weight, body mass gain, carcass fat and BMI were higher in S and HC rats than in C. There were no significant alterations in body length and carcass protein among the groups. Triacylglycerol (TG), total cholesterol (CT), low-density lipoprotein cholesterol (LDL-C) and lipid hydroperoxide (LH) were higher in S and HC rats than in C. High-density lipoprotein cholesterol (HDL-C) decreased in HC rats and total antioxidant substances (TAS) decreased in S and HC rats. There were positive correlations between BMI with carcass fat, BMI with LH and BMI and serum TG concentration. In conclusion, the BMI for male adult Wistar rats ranged between 0.45 and 0.68 g/cm(2). Obesity may be easily estimated from the BMI in rats. Alterations in BMI were associated with dyslipidemic profile and oxidative stress in serum of rats and BMI may predict these adverse consequences of the obesity in rats.

Anxiety levels and wild running susceptibility in rats: assessment with elevated plus maze test and predator odor exposure

It is reported in the literature that nearly 20% of rats are susceptible to displays of wild running (WR) behavior when submitted to high intensity acoustic stimulation. Some characteristics of WR suggest that it can be viewed as a panic-like reaction. This work aimed to test whether WR-sensitive rats show higher levels of anxiety in elevated-plus-maze (EPM) and predator-odor exposure paradigms in comparison with WR-resistant ones. Male adult Wistar rats were submitted to two trials of acoustic stimulation (104 dB, 60 s) in order to assess WR susceptibility. Seven WR-sensitive and 15 WR-resistant rats were evaluated by the EPM test. Other 13 WR-sensitive and 18 WR-resistant animals were submitted to the predator-odor exposure test which consisted of a 10 min-session of free exploration in a specific apparatus containing two odoriferous stimuli: cotton swab imbedded with snake cloacal gland secretion or with iguana feces (control). WR-sensitive rats presented a significantly higher closed-to open-ann-entry ratio in the EPM test. All rats responded with anxiety-like behaviors to the predator odor exposure, although the WR-sensitive ones showed a marked behavioral inhibition regardless of the odor condition. We conclude that WR-sensitive rats present elevated levels of anxiety manifested by means of passive behavioral strategies. (C) 2004 Elsevier B.V. All rights reserved.

SEX-RELATED DIFFERENCES IN CARDIOVASCULAR-RESPONSES TO COMMON CAROTID OCCLUSION IN CONSCIOUS RATS

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female tats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20 s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.

Developmental lead exposure induces depressive-like behavior in female rats

The involvement of neurotoxicants in the etiology of emotional pathologies is becoming an issue in neurotoxicology. Lead (Pb) exposure during childhood has been associated with increased impulsivity, aggressivity, and delinquency. Considering the paucity of experimental studies investigating the involvement of developmental Pb exposure in emotional disorders, our objective was to investigate whether Pb exposure during pregnancy and/or lactation could be related to depressive symptoms in adult male and female rats. Wistar dams received 10 mg of Pb, as Pb acetate, or 13.4 mg of Na acetate, by gavage, daily, during pregnancy and lactation. By cross-fostering at the time of birth, pups were either exposed to Ph or Na acetate during pregnancy only, lactation only, or during both pregnancy and lactation. At 70 days of age, animals were submitted to the open-field test followed by the forced swimming test. Ph levels were measured in the blood of dams (weaning) and pups (after behavioral evaluation). The results demonstrated that exposure to Ph during both pregnancy and lactation induced, in males, an increased emotionality state detected in the open-field test, and in females, depressive-like behavior detected in the forced swimming test. These alterations were observed at residual blood Pb levels (i.e., around 5 mug/dL).

Cardiac benefits of exercise training in aging spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Energy Expenditure and Oxygen Consumption as Novel Biomarkers of Obesity-induced Cardiac Disease in Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Is gender crucial for cardiovascular adjustments induced by exercise training in female spontaneously hypertensive rats?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Environmentally induced antinociception and hyperalgesia in rats and mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Protein synthesis studies in skeletal muscle of aging rats. II. In vitro studies with 0.5M potassium chloride washed polyribosomes

To investigate further the age-related reduction in muscle protein synthesis activity found previously using a crude polyribosome/pH 5 system (Pluskal et al., 1984), a 0.5M KCl washing procedure was utilized to remove the nonribosomal factors from polyribosomes isolated from male Sprague-Dawley rats in the following age groups: young (1 to 2 months), mature (12 months), and aged (22 to 24 months). Using a common source of enriched elongation factor fraction from young animals, it was not possible to demonstrate any significant difference (p > .05) in protein synthesis between the 0.5M KCl-washed polyribosomes isolated from the various age groups. Using a cell-free system containing young salt washed polyribosomes stimulated by the addition of 0.5M KCl-wash fractions, however, it was shown that the mature and aged salt-wash fractions were less (p < .05) active than material from young animals. Thus, the observed decline in protein synthesis efficiency during aging may be attributed to a reduced capacity to promote initiation/elongation by the nonribosomal salt wash fractions of muscle polyribosomes.

A pro-inflammatory role of lymphoid cells in acute pleurisy in rats

The effect of viable splenic lymphoid cells and their constituents (filtrate) on carrageenan-induced acute pleurisy was investigated in rats. Suspensions of lymphoid cells administered intravenously to recipients just prior to initiation of pleurisy enhance both the volume of exudate and cell accumulation in the pleural cavity 3 h after the irritation. Similar results were observed when filtrate of disrupted lymphoid cells was injected either 30 or 5 min before the carrageenan, but not when administered 30 min afterwards. Suspensions of bone marrow cells, on the contrary, were ineffective in producing an enhancement of the parameters studied. When administered into the pleural cavity together with carrageenan, the lymphoid cell filtrate augmented the inflammatory response to the irritant. Nevertheless, it was ineffective, per se, to elicit any local change. It is suggested that lymphoid cells may play a pro-inflammatory role in the initiation of the process by enhancing both the fluid and the cellular components of inflammation.

Effects of acute cold exposure on rectal temperature, blood glucose and plasma free fatty acids in alloxan-diabetic rats

These experiments were carried out to study the effects of acute cold exposure (0-2°C/4 hr) on rectal temperature, blood glucose and plasma free fatty acids (FFA) in alloxan-diabetic rats. Male Wistar rats weighing 170-190 g were used and diabetes was induced by i.v. alloxan injection (40 mg/kg body wt). Cold exposure produced severe hypothermia in diabetic rats. After 4 hr of cold, blood glucose of diabetic rats was reduced from 296±16 to 86t±12 mg/dl (P<0.01), and FFA increased slightly, but was not statistically different (P>0.05) from the initial value. As expected, interscapular brown adipose tissue (IBAT) and retroperitoneal and epididymal white adipose tissues were significantly lower in diabetic than in control rats. Cold exposure reduced total IBAT lipids in control but not in diabetic animals. The results of this experiment suggest that diabetic rats were unable to maintain body temperature in the cold, probably because of a failure to generate an adequate amount of heat by nonshivering thermogenesis in brown adipose tissue.

Pressor, dipsogenic, natriuretic and kaliuretic responses to central carbachol in rats with lesion of the medial septal area

In the present study we investigated the effect of electrolytic lesion of the medial septal area (MSA) on the dipsogenic, natriuretic, kaliuretic and pressor responses elicited by intracerebroventricular (i.c.v.) injection of the cholinergic agonist carbachol. Freely moving rats with sham or MSA lesion (1-7 days and 14-18 days) and a stainless steel cannula implanted into the lateral ventricle were studied. In sham rats, i.c.v. injection of carbachol (7.5 nmol) produced an increase in water intake (10.2 ± 1.5 ml/h), mean arterial pressure (MAP) (35 ± 5 mmHg) and urinary Na+ and K+ excretion (551 ± 83 and 170 ± 17 μEq 120 min, resp.). The pressor (18 ± 3 and 14 ± 4 mmHg, resp.) and natriuretic responses (178 ± 58 and 172 ± 38 μEq 120 min) produced by i.c.v. carbachol in acute or chronic MSA-lesioned rats were reduced. No change was observed in urinary K+ excretion and a reduced water intake (5 ± 1.3 ml/h) was observed only in acute MSA-lesioned rats. These results suggest that the MSA plays an important role for the pressor and natriuretic responses induced by central cholinergic activation in rats. A small influence of this structure on water intake may also be suggested. © 1991.

Free autogenous cartilage grafts to the mandible of rats-histological study.

The present study was designed to histologically evaluate the behavior of free autogenous cartilage grafts to the mandible of rats. A 3-mm segment was removed from the last rib of male adult rats and transplanted fresh to a receptor bed prepared on the mandibular ramus. The results showed that the grafts maintained their vitality up to 120 days and the perichondrium was biologically integrated to the osseous bed. Appositional growth of the grafts was found. New bone formation was observed in close proximity to the grafts, but newly formed trabeculae did not arise from perichondrium.