Chemopreventive effect of diclofenac on mammary carcinogenesis in Sprague-Dawley rats

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.

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.


2011 ◽  
Vol 5 (2) ◽  
pp. 277-282
Author(s):  
Mariem Yusuksawad ◽  
Narongsak Chaiyabutr

Abstract Background: Oxidative stress induces renal dysfunction in diabetes, in which renal mitochondrial disturbance was implicated. Vitamin C (VC) supplementation may ameliorate the renal dysfunction in diabetics. However, it is not clear whether VC supplementation is effective for renal mitochondrial disturbances in diabetes. Objective: Investigate whether long-term continuous VC supplementation could ameliorate the renal mitochondrial disturbances in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-five male Sprague-Dawley rats were used, and diabetes was induced by an injection of STZ. The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and diabetic rats supplemented by vitamin C (STZ-VC). The CON and STZ rats were given tap water, while STZ-VC rats received VC (1 g/L) every day for eight, 24 and 52 weeks. The kidney was isolated and homogenized. Oxygen comsumption (Vo2) was measured in mitochondria homogenate using an oxygen consumption monitor. Based on Vo2 tracings, the respiration control index (RCI) and P/O ratio (= ADP/ O ratio) were measured at week 8, 24 and 52. Results: At week eight, using either glutamate plus malate (for site I) or succinate (for site II) as substrates, both RCI and P/O ratio were not significantly different among three groups. The P/O ratio in STZ and STZ-VC rats increased from eight to 52 weeks after VC supplementation. At week 24, the P/O ratio at site II was normalized in STZ-VC rat. The increased P/O ratio (only site I) and the increased RCI (only site II) of STZ-VC rats were slower than those of STZ rats. Conclusion: Short-term VC supplementation might not influence the renal mitochondrial activity. The long-term VC supplementation could ameliorate the mitochondrial disturbances induced in STZ-induced diabetic rats.


1995 ◽  
Vol 20 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Takashi YAMADA ◽  
Tadahiro INOUE ◽  
Akinori SATO ◽  
Kumiko YAMAGISHI ◽  
Motonobu SATO

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.


2003 ◽  
Vol 284 (1) ◽  
pp. F133-F143 ◽  
Author(s):  
Ki Young Na ◽  
Yoon Kyu Oh ◽  
Jin Suk Han ◽  
Kwon Wook Joo ◽  
Jung Sang Lee ◽  
...  

Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na+ transporters, viz., the Na+-K+-2Cl− cotransporter in the thick ascending limb and the Na+-Cl−cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na+ transporters downstream from the primary site of action. Osmotic minipumps were implanted into Sprague-Dawley rats to deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To prevent volume depletion, all animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The diuretic/natriuretic response was quantified in response to both agents by using quantitative urine collections. Semiquantitative immunoblotting revealed that the abundances of thick ascending limb Na+-K+-2Cl− cotransporter and all three subunits of the epithelial Na+ channel (ENaC) were increased by furosemide infusion. HCTZ infusion increased the abundances of thiazide-sensitive Na+-Cl−cotransporter and β-ENaC in the cortex and β- and γ-ENaC in the outer medulla. Consistent with these results, β-ENaC immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with either diuretic treatment. These increases in the abundance of Na+transporters in response to chronic diuretic treatment may account for the generation of diuretic tolerance associated with long-term diuretic use.


1989 ◽  
Vol 256 (5) ◽  
pp. E682-E685 ◽  
Author(s):  
M. Kalimi

This study was conducted to investigate whether hypertension induced by long-term in vivo administration of dexamethasone in rats could be prevented by the newly synthesized potent antiglucocorticoid drug RU 486. Subcutaneous implantation of 5 mg of dexamethasone pellets in Sprague-Dawley rats resulted in a rapid increase in the blood pressure that remained elevated during the 3 wk of experimental observation. RU 486 (50 mg) administered alone surprisingly showed slight elevation of blood pressure over untreated control animals. However, the blood pressure leveled off to control levels over the next 2 wk. Interestingly, a 50-mg RU 486 pellet implanted along with 5 mg of dexamethasone effectively prevented the dexamethasone-induced increase in blood pressure. RU 486 administered together with dexamethasone prevented dexamethasone-induced diuresis and urinary Na+ excretion. However, RU 486 was unable to reverse the weight loss or involution of thymus observed by long-term treatment with dexamethasone alone. No abnormalities were found in either kidneys or hearts in any of the treated groups under microscopic examination. These results suggest that RU 486 successfully prevented the hypertension produced by the long-term administration of dexamethasone in male Sprague-Dawley rats.


2018 ◽  
Vol 42 (6) ◽  
pp. 498-505 ◽  
Author(s):  
Koffi KOUAME ◽  
Aniekan Imo PETER ◽  
Edidiong Nnamso AKANG ◽  
Misturah ADANA ◽  
Roshila MOODLEY ◽  
...  

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