The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis

CONTEXT: No effective treatment is available for nonalcoholic steatohepatitis in nowadays. OBJECTIVES: To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. METHODS: The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. RESULTS: The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%). The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. CONCLUSIONS: The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis development

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Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01175-06 ◽

2007 ◽

Vol 51 (3) ◽

pp. 1022-1027 ◽

Cited By ~ 13

Author(s):

Kerstin Pfister ◽

Dago Mazur ◽

Jürgen Vormann ◽

Ralf Stahlmann

Keyword(s):

Vitamin E ◽

Wistar Rats ◽

Diet Group ◽

Standard Diet ◽

Joint Cartilage ◽

Cartilage Lesions ◽

Immature Rats ◽

Group A ◽

Group B ◽

Group D

ABSTRACT Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has been demonstrated previously. Identical damages can be induced in immature rats by feeding them a magnesium-deficient diet. The objective of the present study was to investigate whether, in reverse, oral supplementation with magnesium, vitamin E, or both can diminish the typical quinolone-induced arthropathy in juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats were each fed either normal feed (group A), a vitamin E-enriched diet (group B), a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats were sacrificed and cartilage samples from knee joints were examined under a light microscope for the presence of typical quinolone-induced joint cartilage lesions. In addition, magnesium, calcium, and vitamin E concentrations in cartilage and plasma were determined. In the samples from rats fed a normal diet (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups fed an enriched diet, the incidence of specific lesions (n) was significantly lower: group B, n = 10 (41% reduction compared to the incidence for group A; P < 0.05); group C, n = 6 (65% reduction; P < 0.01); and group D, n = 3 (82% reduction; P < 0.01). In comparison to the standard diet, diets with magnesium and vitamin E supplementation resulted in significantly higher magnesium and vitamin E concentrations in plasma and articular cartilage. Supplementation with magnesium and vitamin E alone or in combination may relevantly diminish joint cartilage lesions induced by quinolones in immature rats, with an additive effect of combined supplementation. The data further support the proposed pathomechanism of quinolone-induced arthropathy and the crucial role of magnesium in immature joint cartilage.

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Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

Frontiers in Pharmacology ◽

10.3389/fphar.2021.744483 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiaji Hu ◽

Hanglu Ying ◽

Jie Yao ◽

Longhe Yang ◽

Wenhui Jin ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Underlying Mechanism ◽

Protective Role ◽

Hepatocellular Injury ◽

Deficient Diet ◽

Neuroprotective Effects ◽

Pathway Activation ◽

Elevated Expression ◽

Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

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Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats

Scientific Reports ◽

10.1038/s41598-020-74702-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Juan de Toro-Martín ◽

Tamara Fernández-Marcelo ◽

Águeda González-Rodríguez ◽

Fernando Escrivá ◽

Ángela M. Valverde ◽

...

Keyword(s):

Wistar Rats ◽

Metabolic Diseases ◽

Critical Role ◽

Liver Glycogen ◽

Hormonal Control ◽

Standard Diet ◽

Major Organ ◽

Mtorc1 Pathway

Abstract Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.

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Phytoestrogen-containing diets offer benefits for mouse embryology but lead to fewer offspring being produced

Laboratory Animals ◽

10.1177/0023677219898486 ◽

2020 ◽

Vol 54 (6) ◽

pp. 536-545

Author(s):

Jussi Helppi ◽

Ronald Naumann ◽

Oliver Zierau

Keyword(s):

Transgenic Mice ◽

Diet Group ◽

High Yield ◽

Standard Diet ◽

Potential Health ◽

Protein Sources ◽

Yield And Quality ◽

Experimental Mouse ◽

Standard Diet Group

One of the most commonly used protein sources in rodent diets is soy, which is naturally rich in phytoestrogens. Although phytoestrogens have shown potential health benefits in humans, they may also have the ability to disrupt reproduction. Consequently, there has been a tendency to try to exclude them from rodent diets. In the current study, we investigated whether phytoestrogen content in the mouse diet could affect reproduction in mice used as embryo donors. Donor mice (C57BL/6JOlaHsd) were maintained with three different diets: high phytoestrogen (ca. 400 mg/kg genistein), low phytoestrogen (ca. 10 mg/kg genistein) and standard breeding diet (ca. 120 mg/kg genistein). Mice fed a high phytoestrogen diet had a high yield of plugs, embryos, and injectable embryos, as well as producing good quality embryos. Results from donor mice fed a low phytoestrogen diet were consistently but only slightly inferior, whereas mice fed a standard diet performed the poorest. Interestingly, the largest number of born and weaned offspring were observed when recipient females received embryos from the standard diet group. Sperm yield and quality of stud males did not differ between the groups. We surmize that for experimental endpoints requiring fertilized embryos it may be more beneficial to feed mice a diet containing phytoestrogen, but if the goal is to produce transgenic mice, a diet high in phytoestrogen may be inadvisable. In conclusion, care should be taken when selecting a diet for experimental mouse colonies as phytoestrogen could influence the study outcome.

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The Role of Vitamin E in the Treatment of NAFLD

Diseases ◽

10.3390/diseases6040086 ◽

2018 ◽

Vol 6 (4) ◽

pp. 86 ◽

Cited By ~ 21

Author(s):

Brandon Perumpail ◽

Andrew Li ◽

Nimy John ◽

Sandy Sallam ◽

Neha Shah ◽

...

Keyword(s):

Vitamin E ◽

Nonalcoholic Steatohepatitis ◽

Medical Literature ◽

Ease Of Use ◽

Alpha Tocopherol ◽

Diabetic Patients ◽

Nonalcoholic Fatty Liver ◽

Therapeutic Choice ◽

The Impact

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

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TRANSAMINATION IN MUSCULAR DYSTROPHY AND THE EFFECT OF EXOGENOUS GLUTAMATE: A STUDY ON VITAMIN E DEFICIENT RABBITS, AND MICE WITH HEREDITARY DYSTROPHY

Canadian Journal of Biochemistry and Physiology ◽

10.1139/y63-162 ◽

1963 ◽

Vol 41 (1) ◽

pp. 1423-1432 ◽

Cited By ~ 3

Author(s):

Roland O. Laferté ◽

Harris Rosenkrantz ◽

Louis Berlinguet

Keyword(s):

Body Weight ◽

Vitamin E ◽

Muscular Dystrophy ◽

Glutamic Acid ◽

Alanine Transaminase ◽

Deficient Diet ◽

Terminal Stage ◽

Weight Losses

A study of transaminase enzymes in various tissues of different species was carried out. Rabbits were fed with a vitamin E deficient diet. Controls receiving vitamin E were maintained on the same diet. Animals were killed at intervals and the glutamic-aspartic transaminase (GOT) and the glutamic-alanine transaminase (GPT) levels were determined in the muscle, blood, and liver.Mice with hereditary muscular dystrophy and normal litter mates which served as controls were killed at different stages of the disease and GPT and GOT levels were also determined in the muscle, blood, and liver.Important variations between the two types of dystrophy were noticed. Variations in the levels of GPT and GOT were also significant in blood and liver of dystrophic rabbits.Exogenous glutamic acid was injected to vitamin E deprived rabbits. Body weight losses and the onset of the terminal stage of the disease were much postponed when compared to the vitamin E deprived rabbits which did not receive glutamic acid.A discussion of the possible role of glutamic acid in muscular dystrophy of vitamin E deprived rabbits is presented.

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Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial

Diabetes Care ◽

10.2337/dc19-0167 ◽

2019 ◽

Vol 42 (8) ◽

pp. 1481-1488 ◽

Cited By ~ 41

Author(s):

Fernando Bril ◽

Diane M. Biernacki ◽

Srilaxmi Kalavalapalli ◽

Romina Lomonaco ◽

Sreevidya K. Subbarayan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Randomized Controlled Trial ◽

Vitamin E ◽

Nonalcoholic Steatohepatitis ◽

Controlled Trial ◽

Randomized Controlled

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A role of 1,25(OH)2D3 supplementation in rats with nonalcoholic steatohepatitis induced by choline-deficient diet

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2015.02.011 ◽

2015 ◽

Vol 25 (6) ◽

pp. 556-561 ◽

Cited By ~ 20

Author(s):

H. Han ◽

M. Cui ◽

X. You ◽

M. Chen ◽

X. Piao ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Deficient Diet

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Effect of vitamin E- and selenium-deficiency on rat liver chemiluminescence

Biochemical Journal ◽

10.1042/bj2420383 ◽

1987 ◽

Vol 242 (2) ◽

pp. 383-386 ◽

Cited By ~ 31

Author(s):

C G Fraga ◽

R F Arias ◽

S F Llesuy ◽

O R Koch ◽

A Boveris

Keyword(s):

Vitamin E ◽

Glutathione Peroxidase ◽

Selenium Deficiency ◽

Serum Levels ◽

Hepatic Necrosis ◽

Deficient Diet ◽

Control Value ◽

Weanling Rats

The role of vitamin E and selenium as protective agents against oxidative stress was evaluated by measuring liver chemiluminescence in situ. Weanling rats fed a vitamin E- and selenium-deficient diet showed liver chemiluminescence that was increased 60 and 100% over control values at 16 and 18 days respectively after weaning. At day 21, the double deficiency led to hepatic necrosis, as observed by optical and electron microscopy, and increased serum levels of lactate dehydrogenase and alanine aminotransferase. Single deficiencies, in either vitamin E or selenium, did not produce liver necrosis but increased liver chemiluminescence. Vitamin E deficiency led to a 23 and 50% increase in liver emission at days 18 and 20 respectively; selenium deficiency produced a 64% increase at day 16. The activity of liver selenium-glutathione peroxidase diminished to 13% of the control value in the rats fed doubly deficient and selenium-deficient diets. Activities of superoxide dismutase, catalase and non-selenium-glutathione peroxidase were not modified by the different diets. These results suggest that oxy-radical generation may play a major role in hepatic necrosis in vitamin E- and selenium-deficiency.

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