scholarly journals Atorvastatin Attenuates Bone Loss and Aortic Valve Atheroma in LDLR-/- Mice

Cardiology ◽  
2015 ◽  
Vol 132 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Nalini M. Rajamannan

Atherosclerosis and osteoporosis are the leading causes of mortality and morbidity. The objective of this study was to test this hypothesis in experimental hypercholesterolemia to determine whether statins play a protective role in this process. LDLR-/- mice (n = 60) were allocated to the following groups: group I (n = 20), normal diet; group II (n = 20), 0.25% (w/w) cholesterol diet (w/w), and group III (n = 20), 0.25% (w/w) cholesterol diet + atorvastatin for 48 weeks. Examination of aortic valves (AVA) and femurs for atherosclerosis and calcification markers included micro-CT, special stains, and calcein incorporation. The cholesterol diet induced bone formation in calcified AVA and an increase in macrophage infiltration. Hyperlipidemic bones expressed an increase in osteoclast cells and a decrease in bone formation. Atorvastatin reduced atherosclerosis and bone mineralization in AVA and increased mineralization within femur bones (p < 0.05). Atherosclerosis is present in hyperlipidemic bones and valves as characterized by macrophage and osteoclast infiltration, and it is attenuated by atorvastatin, which may have implications for therapy in the future.

1981 ◽  
Vol 241 (1) ◽  
pp. F85-F93 ◽  
Author(s):  
T. H. Hostetter ◽  
J. L. Olson ◽  
H. G. Rennke ◽  
M. A. Venkatachalam ◽  
B. M. Brenner

Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.


1957 ◽  
Vol 35 (1) ◽  
pp. 25-30 ◽  
Author(s):  
J. LeBlanc

Three groups of 16 albino rats were fed for 45 days, group I, a normal diet of pellets containing 3.5% fat; group II, a diet containing 17% fat in the form of oil; and group III, a diet containing 17% fat in the form of lard. On exposure to cold, the drop of rectal temperature in group I was faster and more pronounced than in group II or group III. It was shown that the larger amount of fat accumulated in the animals fed a high fat diet could not explain, either as a source of energy reserves or as an insulator, the superiority of these diets in maintaining the rectal temperatures at higher levels in the cold. It is postulated that prefeeding of a high fat diet induces changes in the organism which permit higher sustained rates of heat production in the cold.


Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 239
Author(s):  
Fatma M. Ghoneim ◽  
Hani Alrefai ◽  
Ayman Z. Elsamanoudy ◽  
Salwa M. Abo El-khair ◽  
Hanaa A. Khalaf

Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and β cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.


Author(s):  
Sanjiv Karale ◽  
Jagadish V Kamath

Objective: To evaluate the protective effect of daidzein on cyclophosphamide (CPA) induced nephrotoxicity in experimental rats.Methods: The Wistar rats of either sex were randomly divided into five equal groups: Group I (normal saline 1 ml p. o.), Group II (CPA 150 mg/mg i. p), Group III (Daidzein 20 mg/kg p. o.+CPA 150 mg/kg, i. p.), Group IV (Daidzein 40 mg/kg p. o.+CPA 150 mg/kg, i. p.) and Group V (Daidzein 40 mg/kg p. o., alone). Rats of all groups except Group I and Group V treated with CPA in a dosage of 150 mg/mg i. p in the last five days of treatment. Blood samples were collected on 11th day from each rat and subjected for the evaluation of serum markers such as Serum creatinin, serum urea and serum uric acid. Kidney of each rat was excised and subjected for antioxidant parameters evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and histopathological study.Results: Daidzein explored a significant (P<0.001) role in CPA-induced nephrotoxicity by suppressing serum creatinine, serum urea and serum uric acid. Daidzein also demonstrated significant (P<0.001) protection against CPA-induced nephrotoxicity by decreasing MDA level and by elevating the GSH, SOD, catalase at different doses.Conclusions: The obtained results of present study revealed that daidzein attenuates the CPA-induced nephrotoxicity by antioxidant defence action in rats.


1957 ◽  
Vol 35 (1) ◽  
pp. 25-30 ◽  
Author(s):  
J. LeBlanc

Three groups of 16 albino rats were fed for 45 days, group I, a normal diet of pellets containing 3.5% fat; group II, a diet containing 17% fat in the form of oil; and group III, a diet containing 17% fat in the form of lard. On exposure to cold, the drop of rectal temperature in group I was faster and more pronounced than in group II or group III. It was shown that the larger amount of fat accumulated in the animals fed a high fat diet could not explain, either as a source of energy reserves or as an insulator, the superiority of these diets in maintaining the rectal temperatures at higher levels in the cold. It is postulated that prefeeding of a high fat diet induces changes in the organism which permit higher sustained rates of heat production in the cold.


1927 ◽  
Vol 46 (5) ◽  
pp. 699-707 ◽  
Author(s):  
Harry Goldblatt ◽  
Maria Benischek

Of nineteen rats on a complete diet (Group III, Diet + C. L. O.), none showed foci of squamous keratinizing epithelium in abnormal situations. Of twenty-six rats on a diet deficient in vitamins A and D (Group I, Diet—A–D), twenty-three showed metaplastic changes of varying degree in one or more organs; the metaplasia was of columnar, cuboidal, and transitional epithelium to the squamous keratinizing type. Of eighteen rats on a diet deficient in vitamin A alone (Group II, Diet—A), seventeen showed epithelial metaplasia similar to that of Group I in one or more organs. In Groups I (Diet—A–D) and II (Diet—A) the changes occurred in one or more of the following organs: trachea, large bronchi, small bronchi or bronchioles in lung, posterior nares, accessory salivary glands of base of tongue, paraocular, submaxillary, sublingual, and parotid glands, renal pelvis, ureter, and bladder. The metaplastic changes were as extensive in the rats of Group II on a diet deficient in vitamin A alone as in those of Group I which received a diet deficient in vitamins A and D.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Samuel Tung-Hsing Chiang ◽  
Shang-Min Yeh ◽  
Yi-Chen Chen ◽  
Shiun-Long Lin ◽  
Jung-Kai Tseng

The purpose of this study was to investigate the protective role of orally administered taurine against diabetic retinal changes via electroretinogram (ERG) and retinal histology on rabbits. Rabbits were randomly assigned into groups: Group I (vehicle administration only); Group II (diabetes: induced by 100 mg/kg alloxan injection); Group III (diabetes and fed with 200 mg/kg taurine); and Group IV (diabetes and fed with 400 mg/kg taurine). The body weight and blood glucose levels of the rabbits were monitored weekly. The ERG was measured on weeks 5 and 15. Retinal histology was analyzed in the end of the experiment. Results revealed that a taurine supplement significantly ameliorates the alloxan-induced hyperglycemia and protects the retina from electrophysiological changes. Group II showed a significant(P<0.05)change in the mean scotopic b-wave amplitude when compared to that of Group I, whereas the diabetic rabbits treated with taurine (Group III and IV) were analogous to Group I. Histologically, the amount of Bipolar and Müller cells showed no difference(P>0.05)between all groups and when compared with those of Group I. Our study provides solid evidences that taurine possesses an antidiabetic activity, reduced loss of body weight, and less electrophysiological changes of the diabetic retina.


Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Nalini M. Rajamannan ◽  
Malayannan Subramaniam ◽  
Frank Caira ◽  
Stuart R. Stock ◽  
Thomas C. Spelsberg

Background— Calcific aortic valve disease is the most common indication for surgical valve replacement in the United States. The cellular mechanisms of valve calcification are not well understood. We have previously shown that cellular proliferation and osteoblastogenesis are important in the development of valvular heart disease. Lrp5, a known low-density receptor-related protein, plays an essential role in cellular proliferation and osteoblastogenesis via the β-catenin signaling pathway. We hypothesize that Lrp5 also plays a role in aortic valve (AV) calcification in experimental hypercholesterolemia. Methods and Results— We examined the effects of cholesterol and atorvastatin in Watanabe rabbits (n=54). Group I (n=18) received a normal diet, group II (n=18) a 0.25% cholesterol diet, and group III (n=18) a 0.25% (w/w) cholesterol diet with atorvastatin for the development of calcification. The AVs were examined for cellular proliferation, Lrp5/β-catenin, and bone matrix markers. Bone formation was assessed by micro-computed tomography, calcein injection, and osteopontin expression. Low-density lipoprotein with and without atorvastatin was also tested in AV myofibroblasts for cellular proliferation and regulation of the Lrp5/β-catenin pathway. Our results demonstrate that the cholesterol diet induced complex bone formations in the calcified AVs with an increase in the Lrp5 receptors, osteopontin, and p42/44 expression. Atorvastatin reduced bone formation, cellular proliferation, and Lrp5/β-catenin protein levels in the AVs. In vitro analysis confirmed the Lrp5/β-catenin expression in myofibroblast cell proliferation. Conclusion— Hypercholesterolemic AV calcification is attenuated by atorvastatin and is mediated in part by the Lrp5/β-catenin pathway. This developmental pathway may be important in the signaling pathway of this disease.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
S. Saha ◽  
M. K. Mukhopadhyay ◽  
P. D. Ghosh ◽  
D. Nath

The aim of the present study was to investigate the protective role of methanolic leaf extract ofOcimum basilicumL. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P<0.05). The present study indicates that the secondary metabolites ofO. basilicumL. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice.


Author(s):  
Arul Daniel J ◽  
Susmita Das ◽  
Neethu Jayan ◽  
Asha Devi S

Objectives: Various clinically available drugs along with the beneficial action also have drastic side effects due to chronic exposure. In liver, these resulting side effects can be over production of reactive oxygen species, which will further lead to oxidative stress and hepatotoxicity. Therefore, as a preventive measure, the protective role of herbal extracts is being evaluated because of its high success rate and low toxic effects. The primary aim of this study was to evaluate the efficiency of the protective role of Asparagus racemosus is evaluated and studied against methotrexate (MTX)-induced hepatic damage in male Wistar albino rats.Methods: The course of the study was for 14 days. During this experimental study, the animals were categorized into four groups with six rats per group. Group I (positive control) which was treated with normal saline, Group II (negative control) with MTX 20 mg/kg of body weight on 12th day, Group III with A. racemosus 300 mg/kg of body weight + MTX 20 mg/kg on 12th day, and Group IV with A. racemosus 100 mg/kg of body weight + MTX 20 mg/kg on 12th day. On 14th day, the animals were sacrificed, and histopathological as well as antioxidant assays were performed.Results and Conclusion: Assays revealed high lipid peroxidation level and low antioxidant levels in Group II. Meanwhile, in Group III and IV, the levels were restored near to control, which supported the protective role of A. racemosus against MTX-induced hepatic damage. Histopathology evaluation also supported the above-mentioned findings.


Sign in / Sign up

Export Citation Format

Share Document