scholarly journals MO019MATERNAL UNDERNUTRITION AMELIORATES CYST GROWTH IN ADPKD MODEL MICE*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Junpei Yoshikawa ◽  
Nishio Saori ◽  
Fumihiko Hattanda ◽  
Daigo Nakazawa ◽  
Tatsuya Atsumi
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Food Restriction ◽  
Mapk Pathway ◽  
Weight Ratio ◽  
Mtor Pathway ◽  
Nutrient Restriction ◽  
Body Weight Ratio ◽  
Maternal Undernutrition ◽  
Ad Libitum

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The major factors predicting disease progression in ADPKD are total kidney volume, genotype, age, sex. Recently, several studies have suggested that dietary intervention might be a potential treatment to prevent ADPKD progression. On the other hand, it has been reported that low-birth weight infants because of maternal global nutrient restriction are at increased risk for hypertension, type 2 diabetes, and metabolic syndrome and chronic kidney disease. However, little has been reported on relationship between maternal undernutrition and cyst formation in ADPKD. Therefore the purpose of this study is to clarify whether maternal undernutrition is associated with progression in ADPKD. Method We used Pkd1 conditional knockout mice (Pkd1flox/flox･Mx1-Cre mice). The offspring of dams given food ad libitum (control(CON)) and those subjected to nutrient restriction throughout pregnancy (food restriction (FR)) were examined. In FR, nutrient-restricted mothers were given about half amount of food by control mice during pregnancy. After delivery, food for children was given ad libitum. Mice were injected with polyinosinic-polycytidylic acid for 6 consecutive days from postnatal day 5 (P5) to P10 to inactivate Pkd1. We analyzed the phenotype of cystic kidneys by kidney/body weight ratio (2KW/BW), and cystic index (CI) which was defined as the percentage of areas occupied by cysts at P20, 35, 56. We carried out a series of analyses by kidney/body weight ratio, liver /body weight ratio or cystic index (CI) which was defined as the percentage of areas occupied by cysts. Elastica-Masson staining was performed for analyzing tissue fibrosis. The fibrotic index (FI) was expressed as the (fibrotic area/ total non-cystic area) ×100 (%). For evaluation of glomerular hypertrophy, glomerular area was measured in PAS-stained kidney sections using Image J software. The assay of renal function was performed by using UN-ML kit. We also performed western blotting of signaling pathway of proliferation by using whole kidneys. Data are shown as mean ± SEM. Two-tailed Student’s t-test was performed for comparing two groups. Results Food restriction of pregnant dams reduced birth weight. (FR 1.26±0.16 g vs CON 1.55±0.11g). However, FR showed rapid gain weight. There was no significant difference after P20. There were no difference between two groups in 2KW/BW, serum blood urea nitrogen (BUN) levels, CI of kidney and liver until P35. At P56, 2KW/BW was significantly greater in FR (4.59±0.52%) than in CON mice (2.91±0.98%; p＜0.01). CI of both kidney and liver was significantly higher in FR than in CON (Kidney : FR58.1±2.04% vs CON46.3±3.04%; p＜0.05) (Liver : FR11.1±1.41% vs CON 4.89±0.61%; p＜0.001). BUN levels elevated in FR (FR 58.1±5.76mg/dL vs CON 46.3±5.11mg/dL; p＜0.05) .FR showed glomerular sclerosis with PAS staining. Mean Glomerular volume was significantly increased in FR compared with CON (P35: FR 5625±419μm2 vs CON 3255±433μm2; p＜0.001, P56: FR 5780±1195μm2 vs CON 3756±266μm2; p＜0.001) . FR group showed significantly greater fibrosis in kidney (P35: FI 15.3±2.04% vs CON 11.1±1.41%; p＜0.01,P56: FI 42.1±3.2% vs CON 30.8±3.89%; p＜0.001). In western blotting analysis, MAPK pathway and mTOR pathway were suppressed in FR compared with CON at P20. In contrast, MAPK pathway and mTOR pathway were upregulated in FR compared with CON at P56. Conclusion Maternal undernutrition accelerates disease progression via kidney fibrosis, MAPK and mTOR pathway.

scholarly journals Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Nouf Aljobaily ◽  
Michael J. Viereckl ◽  
David S. Hydock ◽  
Hend Aljobaily ◽  
Tsung-Yen Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Body Weight ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Cellular Senescence ◽  
Weight Ratio ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

Exercise and clenbuterol as strategies to decrease the progression of muscular dystrophy in mdx mice

1996 ◽  
Vol 80 (3) ◽  
pp. 734-741 ◽  
Author(s):  
E. E. Dupont-Versteegden
Keyword(s):  
Body Weight ◽  
Muscular Dystrophy ◽  
Weight Ratio ◽  
Morphological Characteristics ◽  
Mdx Mice ◽  
Body Weight Ratio ◽  
Muscle Weight ◽  
Sedentary Group ◽  
Running Activity ◽  
Tetanic Tension

The effects of exercise and the combination of exercise and clenbuterol on progression of muscular dystrophy were studied in mdx mice. At 3 wk of age, mdx mice were randomly assigned to sedentary (MS), exercise (ME), or combined exercise and clenbuterol (MEC) groups. Clenbuterol was given in the drinking water (1.0-1.5 mg . kg body weight-1 . day-1), and exercise consisted of spontaneous running activity on exercise wheels. At 3 mo or 1 yr of age, ventilatory function, contractile properties, and morphological characteristics of the soleus (Sol) and diaphragm (Dia) muscles were measured. The mdx mice receiving clenbuterol ran less than the mice without clenbuterol. The combination of clenbuterol and exercise was associated with an increase in Sol muscle weight and a muscle weight-to-body weight ratio of 30-35% compared with the sedentary group and approximately 20% compared to exercise alone. Myosin and total protein concentrations of the Sol and Dia increased in the MEC group at 1 yr of age only. Normalized active tension was increased in the Dia at 1 yr of age in both the ME and MEC groups by approximately 30%. Absolute tetanic tension of the Sol was increased at both 3 mo and 1 yr of age in the MEC compared with the MS group. At 1 yr of age, there was an additional 23% increase compared with the ME group. Fatigability increased in the MEC group by approximately 25% in the Sol and Dia muscles at both ages compared with the MS and ME groups. Results indicate that exercise and exercise plus clenbuterol decrease the progression of muscular dystrophy. However, different mechanisms may be involved because the combination of clenbuterol and exercise resulted in increased fatigability and the development of deformities, whereas exercise alone did not. Therefore, clenbuterol may not be suitable for use in patients with muscular dystrophy.

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar
Keyword(s):  
Body Weight ◽  
Research Work ◽  
Safety Evaluation ◽  
Weight Ratio ◽  
The Body ◽  
Control Group ◽  
Body Weight Ratio ◽  
Significant Difference ◽  
Manual Group ◽  
Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

Restricted fetal growth and the response to dietary cholesterol in the guinea pig

1999 ◽  
Vol 277 (6) ◽  
pp. R1675-R1682 ◽  
Author(s):  
Karen L. Kind ◽  
Peter M. Clifton ◽  
Arkadi I. Katsman ◽  
Maria Tsiounis ◽  
Jeffrey S. Robinson ◽  
...  
Keyword(s):  
Birth Weight ◽  
Guinea Pig ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Cholesterol Feeding ◽  
Plasma Total Cholesterol ◽  
Maternal Undernutrition ◽  
Prenatal Growth ◽  
Ad Libitum ◽  
Size At Birth

Epidemiological studies suggest that retarded growth before birth is associated with increased plasma total and low-density lipoprotein (LDL) cholesterol concentrations in adult life. Thus perturbations of prenatal growth may permanently alter cholesterol metabolism. To determine directly whether restriction of prenatal nutrition and growth alters postnatal cholesterol homeostasis, the plasma cholesterol response to cholesterol feeding (0.25% cholesterol) was examined in adult guinea pig offspring of ad libitum-fed or moderately undernourished mothers. Maternal undernutrition (85% ad libitum intake throughout pregnancy) reduced birth weight (−13%). Plasma total cholesterol was higher prior to and following 6 wk cholesterol feeding in male offspring of undernourished mothers compared with male offspring of ad libitum-fed mothers ( P< 0.05). The influence of birth weight on cholesterol metabolism was examined by dividing the offspring into those whose birth weight was above (high) or below (low) the median birth weight. Plasma total cholesterol concentrations prior to cholesterol feeding did not differ with size at birth, but plasma total and LDL cholesterol were 31 and 34% higher, respectively, following cholesterol feeding in low- compared with high-birth weight males ( P < 0.02). The response to cholesterol feeding in female offspring was not altered by variable maternal nutrition or size at birth. Covariate analysis showed that the effect of maternal undernutrition on adult cholesterol metabolism could be partly accounted for by alterations in prenatal growth. In conclusion, maternal undernutrition and small size at birth permanently alter postnatal cholesterol homeostasis in the male guinea pig.

scholarly journals The influence of food restriction versus ad libitum feeding of chow and purified diets on variation in body weight, growth and physiology of female Wistar rats

2012 ◽  
Vol 46 (2) ◽  
pp. 101-107 ◽  
Author(s):  
M Moraal ◽  
P P A M Leenaars ◽  
H Arnts ◽  
K Smeets ◽  
B S Savenije ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Restriction ◽  
Wistar Rats ◽  
Statistical Significance ◽  
Blood Parameters ◽  
Calorie Intake ◽  
Restricted Feeding ◽  
Organ Weights ◽  
Female Wistar Rats ◽  
Ad Libitum

Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule.

scholarly journals Protective Role of Pomegranate Peel Extract on Testis in Adult Male Rabbits Treated with Carbon Tetrachloride

2014 ◽  
Vol 38 (1) ◽  
pp. 74-82
Author(s):  
Wassan M. Hussen
Keyword(s):  
Body Weight ◽  
Olive Oil ◽  
Serum Cholesterol ◽  
Weight Ratio ◽  
Body Weight Ratio ◽  
Pomegranate Peel ◽  
Testosterone Concentration ◽  
Testicular Weight ◽  
Pomegranate Peel Extract ◽  
Peel Extract

The aim of the present study is to prepare ethanol extract of Pomegranate peel and the effects of this extract on testicular weight to body weight ratio, Serum cholesterol, testosterone concentration and histopathological changes of testes in rabbits treated with carbon tetrachloride (CCl4). Twenty four adult male rabbits were used. They were divided randomly into four equal groups. Animals were treated for 56 days as following: Rabbits of the 1st group were received 1 ml distal water orally once a day and olive oil 0.5 ml /kg B.W. I.P twice a week as control group. The second group were treated I.P with 500mg / kg B.W. of CCl4 mixing with equal volume of olive oil (0.5 ml/kg B.W.) twice a week (group T1). The third group was received pomegranate peel extract orally (100 mg/kg B.W) once a day and olive oil 0.5 ml /kg B.W. I.P twice a week (group T2). The fourth group were received pomegranate peel extract (100 mg/kg B.W) once a day oral I.P with 500 mg / kg B.W. of CCl4 mixing with equal volume of olive oil (o.5 ml/kg B.W.) twice a week (group T3). Blood samples were collected at (0, 14, 28, 42 and 56) days for measuring testosterone concentration, Serum cholesterol after treatments. Animals weighed and scarified and testis were removed and weighed, Samples of testis were taken for histopathological study. The results of the present study showed that treatment with pomegranate peel extract causes a significant (P>0.05) increase in testicular weight to body weight ratio. Also a significant (P>0.05) decreased of serum cholesterol and a significantly (P>0.05) elevation of testosterone concentration were observed. Histopathological examination of the testis was revealed that the extract of Pomegranate peel protect the testis against lesions caused by CCl4. In conclusion, Pomegranate peel extract could protect the tissue of testicles from CCl4 perhaps, by its anti-oxidative effect of pomegranate peel extract, hence eliminating the deleterious effects or toxic effect of CCl4.

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