The incidence of chronic progressive nephrosis in young Sprague-Dawley rats from two different breeders

1998 ◽  
Vol 32 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Maud Palm

Chronic progressive nephrosis (CPN) in rats may not only become a problem in long-term toxicity studies but also in short-term studies, if the breeding stock is not carefully selected with respect to the kidney function. This paper presents differences in kidney function between young rats of the same strain, Sprague-Dawley, but from two different breeders ('set A' and 'set B' rats). In set A rats, protein in the urine was present in the males, which is a common finding. In set B rats, not only the males but also the females excreted protein in the urine. The method used to detect protein in the urine does not normally show a positive protein result in the young female rats. At the age of 3 months signs of chronic progressive nephrosis were observed in 55% of the males and in 15% of the females in set B. Two months later, the incidence had increased to about 70–80% in males and 50% in females. At 8 months, the incidence was similar, but the severity had increased. These values were compared with those obtained from the set A rats, none of which showed any signs of the disease at the age of 5 months and only 5% of the males and females at the age of 8 months. The results indicated that an increased excretion of protein in the urine may be used as an indicator for chronic progressive nephrosis in the rat and that not only the strain but also the source is important in selecting laboratory rats for toxicity studies.

2020 ◽  
Vol 318 (2) ◽  
pp. R418-R427 ◽  
Author(s):  
Reham H. Soliman ◽  
Jermaine G. Johnston ◽  
Eman Y. Gohar ◽  
Crystal M. Taylor ◽  
David M. Pollock

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.


Biologia ◽  
2013 ◽  
Vol 68 (4) ◽  
Author(s):  
Peter Orendáš ◽  
Ivan Ahlers ◽  
Bianka Bojková ◽  
Monika Kassayová ◽  
Peter Kubatka ◽  
...  

AbstractChemopreventive effect of non-steroidal antiinflammatory drugs (NSAIDs) in mammary carcinogenesis was reported in several studies. In this study, the effect of a nonselective cyclooxygenase inhibitor diclofenac (DICLO) in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats was evaluated. NMU was administered to animals intraperitoneally in two doses of 50 mg kg−1 b.w. within postnatal days 42-48. In experiment A (short-term administration), DICLO was administrated intramuscularly (5 mg kg−1 b.w.) every other day, starting 3 days before and for subsequent 25 days after first NMU injection. In experiment B (long-term administration), DICLO was administered in tap water (0.01 mg ml−1) continually, starting 7 days before and for subsequent 22 weeks after first NMU dose. The study was terminated 22 weeks after the first dose of NMU in both experiments. After DICLO treatment, tumor frequency per group was reduced in both variants of drug administration: in experiment A by 38% and in experiment B by 39.5%. Moreover, DICLO decreased tumor incidence by 11.5% and delayed tumor latency by 14 days in experiment B. In our preventive-curative experiments DICLO decreased some parameters of NMU-induced rat mammary carcinogenesis, mainly the tumor frequency.


1997 ◽  
Vol 9 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Alon Eliakim ◽  
Mark Y. Moromisato ◽  
David Y. Moromisato ◽  
Dan M. Cooper

In this study, the hypothesis that improvements in functional and structural measures could be detected in the young, female rat with only 5 days of moderate treadmill training was tested. Eight-week-old female Sprague-Dawley rats were divided randomly into control (n = 10) and training groups (n = 11). Over the 5-day period, running duration and treadmill speed increased progressively. Maximal running time and gas exchange were measured on Day 6. In trained compared with control rats, maximal running time was 54% greater (p < .005), right hindlimb muscle was 16% heavier (p < .01), and end-exercise respiratory exchange ratio (RER) was 17% lower (p < .05). Substantial metabolic and structural adaptations occurred in young female rats after only 5 days of treadmill training. This protocol may be useful in discovering the initiating mechanisms of the training response in the young organism.


2007 ◽  
Vol 76 (3) ◽  
pp. 371-377 ◽  
Author(s):  
M. Kassayová ◽  
E. Adámeková ◽  
B. Bojková ◽  
P. Kubatka ◽  
I. Ahlers ◽  
...  

The aim of this study was to evaluate the effect of melatonin (MEL) on N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20). Immobilization (2 h per day) began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21%) when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.


2021 ◽  
Author(s):  
Mahfoudh Almuslai Mohammed Abdulghani

Abstract Background Monosodium glutamate (MSG) is commonly used in the Middle East and worldwide as a flavour enhancer in food. MSG is called Chinese salt and is commonly used by the food processing industry, restaurants, and institutional services. The current study was conducted to investigate the effects of monosodium glutamate on the uterine tissue of adult female Sprague Dawley rats with a regular estrus cycle. Results The mean relative values of progesterone and estrogen to the control in the MSG-treated animal group significantly affect (P < 0.05) compared with the control group. The means of the relative lumen area (um2) showed smaller than the control group. Conclusions MSG may cause disturbance in serum progesterone and estrogen levels in young female rats. So, a precautionary utilised for this compound, especially for females under risk factor of hormonal abnormality, is recommended. Further study should be conducted to evaluate the effect of MSG on corpus lutea function.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Omeed Rahimi ◽  
Jay L Kirby ◽  
Jasmina Varagic ◽  
E. Ann Tallant ◽  
Patricia E Gallagher

Doxorubicin (Dox), a commonly used and effective chemotherapeutic agent, often produces cumulative dose-dependent cardiovascular toxicity, resulting in long-term hypertrophy and fibrosis which can lead to heart failure. Adjunct therapies are thus needed to reduce Dox-induced cardiovascular toxicity and enhance long-term quality-of-life in cancer patients, especially in pediatric patients. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system that improves cardiac and vascular function by reducing hypertrophy and fibrosis in various animal models. In this study, juvenile Sprague-Dawley rats (male and female, n = 8-10) were administered Dox (cumulative dose of 22 mg/kg) for 6 week, in the presence and absence of Ang-(1-7) [24 μg/kg/h]. Aortic function was measured using a Vevo 2100 small animal ultrasound system. In both males and females, Dox administration increased pulse wave velocity (PWV), a measure of arterial stiffness, and co-treatment with Ang-(1-7) attenuated the Dox-induced increase (Males - 5.6 ± 0.5, Sham; 9.7 ± 1.4, Dox; 7.8 ± 0.6 m/s, Dox/Ang-(1-7), p < 0.01; Females - 5.1 ± 0.5, Sham; 14.3 ± 1.5, Dox; 7.7 ± 1.2 m/s, Dox/Ang-(1-7), p < 0.001); Ang-(1-7) alone had no effect. Dox increased aortic thickness and decreased aortic diameter at systole in males only, which was attenuated by Ang-(1-7) (aortic thickness - 0.28 ± 0.01, Sham; 0.33 ± 0.01, Dox; 0.28 ± 0.01 mm, Dox/Ang-(1-7), p < 0.01; aortic diameter - 2.8 ± 0.6, Sham; 2.3 ± 0.1, Dox; 2.5 ± 0.1 mm, Dox/Ang-(1-7); p < 0.01). No change in aortic thickness or diameter was observed following treatment with Ang-(1-7) alone. Conversely, Dox increased fibrosis in female aorta only, measured by immunohistochemistry with Picrosirius red, which was attenuated by Ang-(1-7) (5.4 ± 0.3, Sham; 7.2 ± 0.6, Ang-(1-7); 12.8 ± 2.0, Dox; 8.0 ± 1.0%, Dox/Ang-(1-7); p < 0.001). These results demonstrate that Dox causes aortic dysfunction in both males and females, albeit through different mechanisms—an increase in aortic hypertrophy in males and aortic fibrosis in females. Ang-(1-7) attenuated both the hypertrophy and fibrosis, suggesting that treatment with the heptapeptide hormone may serve as an effective adjuvant to improve Dox-induced aortic dysfunction.


2011 ◽  
Vol 40 (1) ◽  
pp. 40-54 ◽  
Author(s):  
Yuval Ramot ◽  
Moti Rosenstock ◽  
Ety Klinger ◽  
Dizza Bursztyn ◽  
Abraham Nyska ◽  
...  

Glatiramer acetate (GA), the active ingredient in Copaxone®, is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, without systemic effects or death. Protiramer administration was not as well tolerated as GA and led to dose- and time-related mortalities, probably mediated through severe injection-site lesions both in rats and in monkeys. Bridging fibrosis in the liver and severe progressive nephropathy were seen in rats. A dose-related increase in eosinophils was observed in monkeys. The protiramer toxicity studies show that minor variations in the manufacturing of glatiramoids may lead to significant toxic effects. It is therefore essential that the safety of any new glatiramoid be studied in long-term preclinical studies before exposing humans.


2006 ◽  
Vol 82 (4) ◽  
pp. 285-291 ◽  
Author(s):  
H. J. Lee ◽  
S. H. Kim ◽  
S. Y. Choi ◽  
Y. M. Gimm ◽  
J. K. Pack ◽  
...  

2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.


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