scholarly journals Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs’ Livers

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 953
Author(s):  
Vitor Teixeira ◽  
Ibrahim Mohamed ◽  
Jean-Claude Lavoie
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Guinea Pigs ◽  
Early Life ◽  
Specific Activity ◽  
Enzyme Level ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Deficient Diet ◽  
Protein Levels

Premature neonates are submitted to an early-life oxidative stress from parenteral nutrition, which is vitamin C (VC) deficient and induces low endogenous levels of glutathione. The oxidative stress caused by these deficiencies may permanently affect liver glycolysis and lipogenesis. This study evaluates the short- and long-term effects of neonatal VC and cysteine deficient diets on redox and energy metabolism. Three-day-old Hartley guinea pigs from both sexes were given a regular or a deficient diet (VC, cysteine, or both) until week 1 of life. Half of the animals were sacrificed at this age, while the other half ate a complete diet until 12 weeks. Liver glutathione and the activity and protein levels of glucokinase, phosphofructokinase, and acetyl-CoA-carboxylase were measured. Statistics: factorial ANOVA (5% threshold). At 1 week, all deficient diets decreased glutathione and the protein levels of glucokinase and phosphofructokinase, while cysteine deficiency decreased acetyl-CoA-carboxylase levels. A similar enzyme level was observed in control animals at 12 weeks. At this age, VC deficiency decreased glutathione, while cysteine increased it. Acetyl-CoA-carboxylase protein levels were increased, which decreased its specific activity. Early-life VC and cysteine deficiencies induce neonatal oxidative stress and an adult-like metabolism, while predisposing to increased lipogenic rates during adulthood.

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

2018 ◽  
Vol 88 (5-6) ◽  
pp. 263-269
Author(s):  
Seong-Hoon Park ◽  
A Lum Han ◽  
Na-Hyung Kim ◽  
Sae-Ron Shin
Keyword(s):  
Liver Biopsy ◽  
Vitamin C ◽  
Nonalcoholic Steatohepatitis ◽  
Guinea Pigs ◽  
Normal Diet ◽  
High Dose ◽  
Biochemical Tests ◽  
Deficient Diet ◽  
Histological Improvement ◽  
Vit C

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

scholarly journals Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Zhai ◽  
Wei Xu ◽  
Yayun Liu ◽  
Kun Qian ◽  
Yanling Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Regulatory Gene ◽  
Deficient Diet ◽  
Jnk Pathway ◽  
Beneficial Effects ◽  
Protein Levels ◽  
And Oxidative Stress

Background. Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. Methods. C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 μmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. Results. The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. Conclusions. HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and β-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.

Regulation of acetyl-CoA carboxylase

2006 ◽  
Vol 34 (2) ◽  
pp. 223-227 ◽  
Author(s):  
R.W. Brownsey ◽  
A.N. Boone ◽  
J.E. Elliott ◽  
J.E. Kulpa ◽  
W.M. Lee
Keyword(s):  
Active Sites ◽  
Specific Activity ◽  
Splice Variants ◽  
Acid Synthesis ◽  
Regulatory Elements ◽  
Hormone Action ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Regulatory Molecule ◽  
Malonyl Coa

Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530–560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.

scholarly journals Glucose-dependent induction of acetyl-CoA carboxylase in rat hepatocyte cultures

1984 ◽  
Vol 221 (2) ◽  
pp. 343-350 ◽  
Author(s):  
S Giffhorn ◽  
N R Katz
Keyword(s):  
Enzyme Activity ◽  
Enzyme Level ◽  
Enzyme Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Enzyme Protein ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Adult Rats ◽  
Hepatocyte Cultures

The carbohydrate-dependent long-term regulation of acetyl-CoA carboxylase was studied in primary hepatocyte cultures from adult rats. (1) The enzyme activity was increased 2-fold either by elevation of the glucose concentration to 20mM or by enhancement of the insulin concentration to 0.1 microM. Simultaneous increases in glucose and insulin resulted in a 5-fold increase in the enzyme activity. (2) As shown by immunochemical titration, the enhancement of the enzyme activity was due to an increase in the enzyme protein. (3) Incorporation of [35S]methionine and immunoprecipitation of the enzyme revealed that the increase in enzyme protein was due to an increased rate of enzyme synthesis. The rate of enzyme degradation remained essentially unchanged. (4) The glucose- and insulin-dependent induction of acetyl-CoA carboxylase was prevented by the addition of alpha-amanitin (10 microM) or cordycepin (10 microM), indicating a transcriptional regulation of the enzyme level. (5) The parallel induction of acetyl-CoA carboxylase and of ATP citrate lyase indicates a co-ordinate long-term regulation of lipogenic enzymes.

scholarly journals Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

2007 ◽  
Vol 98 (6) ◽  
pp. 1116-1119 ◽  
Author(s):  
Jens Lykkesfeldt ◽  
Gilberto Perez Trueba ◽  
Henrik E. Poulsen ◽  
Stephan Christen
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Vitamin C ◽  
Lipid Oxidation ◽  
Protein Oxidation ◽  
Guinea Pigs ◽  
Vitamin C Deficiency ◽  
Markers Of Oxidative Stress ◽  
Selective Preservation ◽  
The Brain

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0·001), tocopherols (P < 0·001) and glutathione (P < 0·001), and a decrease in superoxide dismutase activity (P = 0·005) in the liver, while protein oxidation was significantly increased (P = 0·011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0·001), but in contrast to the liver, ascorbate oxidation (P = 0·034), lipid oxidation (P < 0·001), DNA oxidation (P = 0·13) and DNA incision repair (P = 0·014) were all increased, while protein oxidation decreased (P = 0·003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

scholarly journals Pre-administration of vitamin C reduces exercise-induced oxidative stress in untrained subjects

2014 ◽  
Vol 66 (3) ◽  
pp. 1179-1185 ◽  
Author(s):  
Florin-Petrut Trofin ◽  
Marin Chirazi ◽  
Cezar Honceriu ◽  
Paula Drosescu ◽  
Gabriela Grădinariu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Specific Activity ◽  
Serum Markers ◽  
Antioxidant Defenses ◽  
Dietary Vitamin ◽  
Bicycle Exercise ◽  
Physically Active ◽  
Markers Of Oxidative Stress ◽  
Exercise Induced

We investigated the effects of a 40 min bout of bicycle exercise, and the effects of vitamin C administration 12 h before exercise, on the serum markers of oxidative stress in young untrained subjects. Increased levels of malondialdehyde, the marker of the lipid peroxidation, and a decrease in specific activity of the antioxidant enzyme glutathione peroxidase that were observed as a result of exercise, pointed to the presence of exercise-induced oxidative stress. These markers were reduced by pre-administration of vitamin C. The results suggest that physically active subjects could increase their daily dietary vitamin C intake in order to reinforce their antioxidant defenses prior to exercise training.

scholarly journals Therapeutic Effects of Ethanolic Extract of Polygonum limbatum meism Against Reproductive Toxicity Induced by Cadmium in Male Guinea Pigs (Cavia porcellus)

2021 ◽  
Vol 8 ◽  
Author(s):  
Brice Menkem ◽  
Bertin Narcisse Vemo ◽  
Megnimeza Martine Astride Tsambou ◽  
Tadiesse Lavoisier Fonou ◽  
Nguedia Arius Baulland Dongmo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Guinea Pigs ◽  
Cadmium Chloride ◽  
Sperm Count ◽  
Antioxidant Properties ◽  
Ethanolic Extract ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects

This study aimed at evaluating the therapeutic effects of ethanolic extract of Polygonum limbatum meism (EEPLM) on the reproductive parameters of male Guinea pigs exposed to cadmium chloride. Thirty-six male guinea pigs were randomly assigned to six treatment groups (with six animals per group). Group 1 (DW) received distilled water orally; group 2 (Cd), negative control, was treated with cadmium chloride at a dose of 26.25 mg/kg body weight (bw); while group 3 (VitC), positive control, was given 26.25 mg of cadmium chloride/kg bw and 100 mg of vitamin C, and groups 4, 5, and 6 were treated, respectively, with EEPLM at doses of 50, 100, and 200 mg/kg bw in addition to cadmium chloride (26.25 mg/kg bw). After 90 days, all animals were sacrificed, and data related to reproduction, toxicity, and oxidative stress were collected. Results revealed a significant decrease (p &lt; 0.05) of serum levels of creatinine, urea, alanine, and aspartate amino transferases in guinea pigs treated with cadmium chloride and EEPLM compared to the negative control group (Cd). The weight of the bulbo-urethral gland was significantly (p &lt; 0.05) decreased in animals exposed to cadmium chloride and treated with vitamin C or EEPLM compared to the negative control (Cd). Guinea pigs orally receiving cadmium chloride and EEPLM showed significantly (p &lt; 0.05) increased motility, sperm count, spermatozoa with entire plasma membrane, and percentage of normal spermatozoa with reference to the negative control (Cd). The serum level of testosterone increased insignificantly (p &gt; 0.05) in animals given cadmium and EEPLM compared to the negative control (Cd). Animals co-administered cadmium chloride and EEPLM recorded a significantly (p &lt; 0.05) reduced level of MDA, activities of SOD, and total peroxidases compared to the group that received cadmium chloride (Cd) only. In conclusion, cadmium chloride induced reproductive impairments by generating oxidative stress. However, the administration of EEPLM can mitigate these adverse effects due to its antioxidant properties.

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