scholarly journals Dietary Intervention Accelerates NASH Resolution Depending on Inflammatory Status with Minor Additive Effects on Hepatic Injury by Vitamin E Supplementation

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 808
Author(s):  
Julie Hviid Klaebel ◽  
Günaj Rakipovski ◽  
Birgitte Andersen ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg
Keyword(s):  
Vitamin E ◽  
Guinea Pig ◽  
Lipid Accumulation ◽  
Guinea Pigs ◽  
Dietary Intervention ◽  
Liver Weight ◽  
High Dose ◽  
Chow Diet ◽  
Lifestyle Modifications ◽  
Inflammatory Status

Despite the lack of effective pharmacotherapy against nonalcoholic steatohepatitis (NASH) and liver fibrosis, vitamin E (vitE) supplementation and lifestyle modifications are recommended for the management of NASH due to promising clinical results. We recently reported a positive effect of supplementation with 800 IU vitE and atorvastatin on NASH resolution in guinea pigs. In the present study, we investigated the effect of high-dose vitE therapy combined with dietary intervention against progressive NASH and advanced fibrosis in the guinea pig model. Sixty-six guinea pigs received either high-fat (HF) or standard guinea pig chow diet (Control) for 25 weeks. Prior to eight weeks of intervention, HF animals were allocated into groups; dietary intervention (Chow) or dietary intervention with 2000 IU/d vitE supplementation (CvitE). Both Chow and CvitE reduced dyslipidemia, hepatic lipid accumulation and liver weight (p < 0.05), while CvitE further decreased hepatocellular ballooning (p < 0.05). Subanalyses of individual responses within intervention groups showed significant correlation between the hepatic hallmarks of NASH and lipid accumulation vs. inflammatory state (p < 0.05). Collectively, our results indicate that individual differences in sensitivity towards intervention and inflammatory status determine the potential beneficial effect of dietary intervention and high-dose vitE supplementation. Moreover, the study suggests that inflammation is a primary target in NASH treatment.

scholarly journals Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2834 ◽  
Author(s):  
Julie Hviid Klaebel ◽  
Mia Skjødt ◽  
Josephine Skat-Rørdam ◽  
Günaj Rakipovski ◽  
David H. Ipsen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Guinea Pig ◽  
Target Genes ◽  
Dietary Intervention ◽  
Liver Weight ◽  
Diet Change ◽  
Lifestyle Modifications ◽  
Low Fat ◽  
Low Fat Diet ◽  
Guinea Pig Model

Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints.

Effect of short-term vitamin E deficiency on guinea pig skeletal muscle myoglobin

1959 ◽  
Vol 197 (2) ◽  
pp. 491-493 ◽  
Author(s):  
A. D. Bender ◽  
D. D. Schottelius ◽  
B. A. Schottelius
Keyword(s):  
Skeletal Muscle ◽  
Vitamin E ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Short Term ◽  
Vitamin E Deficiency ◽  
Deficient Diet ◽  
Wet Weight ◽  
Masseter Muscles ◽  
Nitrogen Percentage

Myoglobin concentration was determined in gastrocnemius and masseter muscles of guinea pigs maintained up to 15 days on vitamin E-deficient and vitamin E-supplemented diets. A statistically significant increase in myoglobin was noted in muscles of animals on the deficient diet for 15 days. That the increase was real and not apparent was attested by studies of total nitrogen, noncollagen nitrogen, percentage of solids and muscle wet weight, all of which were the same in control and experimental muscles. Histological sections and creatine excretion studies confirmed the impression of mild, incipient nutritional dystrophy.

scholarly journals NUTRITIONAL MUSCULAR DYSTROPHY IN THE GUINEA PIG AND RABBIT

1931 ◽  
Vol 54 (2) ◽  
pp. 145-165 ◽  
Author(s):  
Marianne Goettsch ◽  
Alwin M. Pappenheimer
Keyword(s):  
Vitamin E ◽  
Muscular Dystrophy ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Unknown Factor ◽  
Nutritional Muscular Dystrophy

A diet is described, which leads to a progressive, highly selective, and ultimately fatal dystrophy of the voluntary muscles. Guinea pigs and rabbits are susceptible, rats resistant. The diet used is complete in known requirements, except for vitamin E; the addition of this factor, however, does not prevent the development of the disease. The lesions are not due to inanition, infection, or scurvy, and must be referred to some still unknown factor.

Radioprotective Effects of Amifostine, L-Carnitine and Vitamin E in Preventing Early Salivary Gland Injury due to Radioactive Iodine Treatment

2019 ◽  
Vol 15 (4) ◽  
pp. 395-404 ◽  
Author(s):  
Nese Torun ◽  
Asli Muratli ◽  
Burcu Dirlik Serim ◽  
Alev Ergulen ◽  
Gulay Durmus Altun
Keyword(s):  
Single Dose ◽  
Salivary Gland ◽  
Vitamin E ◽  
Guinea Pigs ◽  
Radioactive Iodine ◽  
Thyroid Tissue ◽  
The Body ◽  
High Dose ◽  
Remnant Thyroid ◽  
Iodine Treatment

<P>Objective: Standard treatment of differentiated thyroid cancer includes total thyroidectomy and high-dose Radioactive Iodine Therapy (RIT) for ablation of remnant thyroid tissue. When administered systemically, RIT can cause radiation-induced damage in non-targeted normal tissues. The aim of the present study was to compare the protective effects of amifostine (AMI), LCarnitine (LC), and Vitamin E (EVIT) against high dose radioactive iodine treatment induced Salivary Gland (SG) damage using SG scintigraphy and histopathological examination. Methods: Forty adult guinea pigs were studied. Twenty guinea pigs receive 555-660 MBq 131Iodine intraperitoneally (IP) to ablate the thyroid and impair the parenchymal function of the SGs. The animals were divided into eight groups as follows: (1) Group 1 (control): 1 mL IP PS (physiological saline); (2) Group 2: single dose of 200 mg/kg IP AMI one hour prior to 1 mL IP PS; (3) Group 3: 200 mg/kg IP LC and 1 mL IP PS for 10 days; (4) Group 4: 40 mg/kg intramuscular (IM) EVITand 1 mL IP PS for 10 days; (5) Group 5: IP RIT after premedication; (6) Group 6: Single dose of 200 mg/kg IP AMI one hour prior to RIT and IP RIT after premedication; (7) Group 7: IP RIT after premedication and 200 mg/kg IP LC for 10 days starting one day before RIT; and (8) Group 8: IP RIT after premedication and 40 mg/kg IM EVIT for 10 days starting one day before RIT. Scintigraphy was performed 1 month after treatment. SGs were examined by light microscopy and a histopathological scoring system was used to assess the degree of SG damage. Results: There were significant differences in the body weight and thyroid hormone levels between the groups after treatment. Conclusion: The individual use of AMI, LC and EVIT for radioprotection yield different levels of protection against radioactive iodine treatment injury in SGs; however, none of the agents could provide absolute protection at the doses administered in this experimental model.</P>

Aspirin impairs antioxidant system and causes peroxidation in human erythrocytes and guinea pig myocardial tissue

2001 ◽  
Vol 20 (1) ◽  
pp. 34-37 ◽  
Author(s):  
I Durak ◽  
M Karaayvaz ◽  
M Y B Çimen ◽  
A Avci ◽  
O B Çimen ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Antioxidant System ◽  
Guinea Pigs ◽  
Heart Tissue ◽  
Human Erythrocytes ◽  
High Dose ◽  
Guinea Pig Heart ◽  
Blood Samples ◽  
Dose Aspirin ◽  
Scavenger Activity

This study aims to investigate possible effects of aspirin treatment on cellular oxidant/antioxidant system. In the first part of the study, 15 guinea pigs were given aspirin at three different doses (2200, 440 and 10 mg/kg/day) for 30 days and five were fed on the same diet without aspirin. After a month, animals were killed and their hearts were removed for use in analyses. In the other part, after fasting blood samples were obtained from 11 volunteer subjects, they were given aspirin (approximately 10 mg/kg/day) for 30 days and second blood samples were obtained after 1 month. Five volunteer subjects also participated as placebo control. Oxidant/antioxidant parameters, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nonenzymatic superoxide scavenger activity (NSSA), susceptibility to oxidation (SO) and antioxidant potential (AOP) values, were assayed in the samples. Antioxidant system was found to be impaired in the heart tissue from guinea pigs and in the erythrocytes from volunteer subjects. AOP and NSSA values were lower and MDA higher after aspirin treatment in both heart tissues and erythrocytes. In guinea pig heart tissue, SO was lower, but GSH-Px and CAT were unchanged after aspirin treatment. In human erythrocytes, SO was unchanged, but GSH-Px and CAT activities were increased after aspirin treatment. Changes in guinea pig heart tissues from animals treated with higher aspirin doses were more drastic relative to those of human erythrocytes, but no meaningful differences were observed between analysis parameters of control and lower-dose (10 mg/kg/day) aspirin-treated animals. Our results suggest that high-dose aspirin exerts significant toxicity to guinea pig myocardium and normal dose aspirin may cause peroxidation in the human erythrocytes due to its oxidant potential. We suppose that antioxidant supplementation may be beneficial for the people using aspirin for longer periods in order to prevent peroxidation damages.

scholarly journals Bone Benefits of Fish Oil Supplementation Depend on its EPA and DHA Content

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2701
Author(s):  
Haissam Abou-Saleh ◽  
Allal Ouhtit ◽  
Ganesh V. Halade ◽  
Md Mizanur Rahman
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Fish Oil ◽  
Signaling Pathways ◽  
Dietary Intervention ◽  
High Dose ◽  
Chow Diet ◽  
Bone Resorption Marker ◽  
Mineral Density

The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%–4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.

scholarly journals Characterization of a novel intratracheal aerosol challenge model of Brucella melitensis in guinea pigs

2018 ◽  
Author(s):  
M.E. Hensel ◽  
D.G. Garcia-Gonzalez ◽  
S.P. Chaki ◽  
J. Samuel ◽  
A.M. Arenas-Gamboa
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Guinea Pig ◽  
Lymph Nodes ◽  
Guinea Pigs ◽  
Brucella Melitensis ◽  
Recurrent Fever ◽  
Human Brucellosis ◽  
High Dose ◽  
Post Inoculation

AbstractB. melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B. melitensis at low dose (101 to 103) or high dose (106 to 108) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12-17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 107 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8×105 to 4.2×106 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.Author summaryBrucellosis is caused by a gram-negative, intracellular bacterial pathogen with a worldwide distribution and affects up to half a million people per year. It is a neglected zoonosis that impacts not only animal welfare, but also exert economic pressure on afflicted individuals through loss of wages and decreased productivity. In people, recurrent fever, malaise, and anorexia accompanied by enlargement of the spleen and lymph nodes are common clinical symptoms of infection. The mouse model has been used extensively to study the pathogenesis of brucellosis, but there are drawbacks to extrapolating studies in mice to develop vaccines or therapeutics for people. Mice are frequently inoculated via intraperitoneal injection, which is an artificial means of producing disease that does not mimic natural transmission or disease features, such as fever. An animal model is needed that can be infected through natural transmission routes and subsequently develop a syndrome that matches clinical disease seen in people in order to study the pathogenesis of disease and to develop vaccines and therapeutics. The guinea pig offers an improvement on the mouse model because it can be infected via aerosol inoculation and develops fever, a humoral immune response, systemic colonization, and macroscopic and microscopic lesions of disease. As such, guinea pigs could be used a more biologically relevant model for evaluation of host-pathogen interactions.

scholarly journals Feeding and breeding of laboratory animals. XII. A note on the breeding of guinea-pigs without fresh green food

1950 ◽  
Vol 48 (3) ◽  
pp. 338-345 ◽  
Author(s):  
H. M. Bruce
Keyword(s):  
Ascorbic Acid ◽  
Vitamin E ◽  
Guinea Pig ◽  
Reproductive Performance ◽  
Guinea Pigs ◽  
Laboratory Animals ◽  
Breeding Colony ◽  
Vitamin E Deficiency ◽  
Green Food ◽  
Continuous Reproduction

1. Five generations of guinea-pigs bred successfully on diet 18 supplemented with crystalline ascorbic acid but without fresh green food.2. No difference in reproductive performance was found between these animals and those of the normal breeding colony receiving unlimited supplies of fresh abbage.3. Symptoms of vitamin E deficiency appeared among some young of the fourth and fifth generations, showing that diet 18 alone contained barely enough of this factor for continuous reproduction througy many generations.4. Diet 18, supplemented by hay and fresh green food to supply vitamin C and additional vitamin E, provides all the essential factors required by the guinea-pig.

scholarly journals Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever

2006 ◽  
Vol 74 (11) ◽  
pp. 6085-6091 ◽  
Author(s):  
K. E. Russell-Lodrigue ◽  
G. Q. Zhang ◽  
D. N. McMurray ◽  
J. E. Samuel
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Q Fever ◽  
Clinical Signs ◽  
Cell Vaccine ◽  
High Dose ◽  
Duration Of Response ◽  
Histopathologic Evaluation ◽  
Clinical Illness ◽  
Acute Q Fever

ABSTRACT Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 101 to 106 organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

Glycogen in guinea pig neutrophils: Ultrastructural study of neutrophils at the intradermal site of BCG injection

1983 ◽  
Vol 41 ◽  
pp. 726-727
Author(s):  
Corazon D. Bucana
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Electron Density ◽  
Peritoneal Cavity ◽  
Ultrastructural Study ◽  
Guinea Pigs ◽  
Random Distribution ◽  
Glycogen Content ◽  
Polymorphonuclear Neutrophils ◽  
Ultrastructural Studies

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.

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