Beta vulgaris L. (Beetroot) Methanolic Extract Prevents Hepatic Steatosis and Liver Damage in T2DM Rats by Hypoglycemic, Insulin-Sensitizing, Antioxidant Effects, and Upregulation of PPARα

The present study examined if methanolic beetroot extract (BE) could prevent dyslipidemia and hepatic steatosis and damage in a type-2 diabetes mellitus (T2DM) rat model and studied some mechanisms of action. T2DM was induced in adult male Wistar rats by a low single dose of streptozotocin (STZ) (35 mg/kg, i.p) and a high-fat diet (HFD) feeding for 5 weeks. Control or T2DM rats then continued on standard or HFDs for another 12 weeks and were treated with the vehicle or BE (250 or 500 mg/kg). BE, at both doses, significantly improved liver structure and reduced hepatic lipid accumulation in the livers of T2DM rats. They also reduced body weight gain, serum glucose, insulin levels, serum and hepatic levels of cholesterol, triglycerides, free fatty acids, and serum levels of low-density lipoproteins in T2DM rats. In concomitant, they significantly reduced serum levels of aspartate and alanine aminotransferases, hepatic levels of malondialdehyde, tumor-necrosis factor-α, interleukin-6, and mRNA of Bax, cleaved caspase-3, and SREBP1/2. However, both doses of BE significantly increased hepatic levels of total glutathione, superoxide dismutase, and mRNA levels of Bcl2 and PPARα in the livers of both the control and T2DM rats. All of these effects were dose-dependent and more profound with doses of 500 mg/kg. In conclusion, chronic feeding of BE to STZ/HFD-induced T2DM in rats prevents hepatic steatosis and liver damage by its hypoglycemic and insulin-sensitizing effects and its ability to upregulate antioxidants and PPARα.

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D-limonene in diabetic rats

Journal of Renal Injury Prevention ◽

10.34172/jrip.2021.24 ◽

2021 ◽

Vol 10 (3) ◽

pp. e24-e24

Author(s):

Shahrokh Bagheri ◽

Mostafa Moradi Sarabi ◽

Mohammadreza Gholami ◽

Vahideh Assadollahi ◽

Reza Mohammadrezaei Khorramabadi ◽

...

Keyword(s):

Real Time ◽

Kidney Tissue ◽

Serum Levels ◽

Diabetic Control ◽

Serum Glucose ◽

Diabetic Rats ◽

Tissue Homogenate ◽

Control Group ◽

Mrna Levels ◽

Male Wistar Rats

Introduction: Diabetes mellitus (DM) is a multi-factorial condition associated with oxidative stress. Limonene, as a plant-derived antioxidant, can be used for treating DM. Objectives: An investigation on antioxidant effects in diabetic rats exposed to D-limonene. Materials and Methods: Sixty male Wistar rats were categorized into six groups as follows: control (healthy rats), diabetic control (untreated diabetic rats), sham glibenclamide, diabetic glibenclamide, sham limonene, and finally diabetic limonene. Alloxan (100 mg/dL) was infused intraperitoneally to induce type 1 diabetes in rats. Rats in certain groups were given limonene (100 mg/dL) and glibenclamide (10 mg/dL) orally for 8 weeks. Subsequently, animals were killed, and their kidneys were removed. Serum levels of biochemical factors (including serum creatinine, urea, and glucose) were determined, and factors such as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) were measured in kidney tissue homogenate. The gene expression and enzymatic activity of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney were measured by real-time polymerase chain reaction (real-time PCR) and spectrophotometry, respectively. Results: Limonene treatment significantly decreased serum glucose, creatinine, and urea. Additionally, MDA, MPO, and NO significantly decreased while GSH increased after treatment with limonene. Real-time RT-PCR showed significant elevation (P<0.05) in mRNA levels of GPx, CAT, and SOD in the limonene-treated compared with the diabetic control group. Conclusion: Our results demonstrated that limonene as an herbal antioxidant had better effects on antioxidant markers compared to glibenclamide in rat models of diabetes.

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A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y11-074 ◽

2011 ◽

Vol 89 (10) ◽

pp. 759-766 ◽

Cited By ~ 2

Author(s):

Horacio Rivera ◽

Martha S. Morales-Ríos ◽

Wendy Bautista ◽

Mineko Shibayama ◽

Víctor Tsutsumi ◽

...

Keyword(s):

Liver Damage ◽

Inflammatory Responses ◽

Acute Liver Damage ◽

Tnf Α ◽

Male Wistar Rats ◽

Anti Inflammatory ◽

Factor Α ◽

Glutamyl Transpeptidase

There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage. To achieve this, CCl4 (4 g·kg–1, per os) was administered to male Wistar rats, followed by either 2-fluoro-4′-methoxystilbene (FME) or 2,3-difluoro-4′-methoxystilbene (DFME) (10 mg·kg–1, per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl4 administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl4-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

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β-Sitosterol Alters the Inflammatory Response in CLP Rat Model of Sepsis by Modulation of NFκB Signaling

BioMed Research International ◽

10.1155/2021/5535562 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Sara Kasirzadeh ◽

Mohammad Hossein Ghahremani ◽

Neda Setayesh ◽

Fereshteh Jeivad ◽

Amir Shadboorestan ◽

...

Keyword(s):

Inflammatory Response ◽

Bacterial Infections ◽

Sham Group ◽

Cecal Ligation ◽

Serum Levels ◽

Protective Role ◽

Mrna Levels ◽

Tnf Α ◽

Male Wistar Rats ◽

Host Inflammatory Response

Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results. Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats ( p < 0.05 ). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group ( p < 0.05 ). Conclusion. βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients.

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The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

Acta Endocrinologica ◽

10.1530/eje.0.1440529 ◽

2001 ◽

pp. 529-534 ◽

Cited By ~ 9

Author(s):

A Lopez-Calderon ◽

I Ibanez de Caceres ◽

L Soto ◽

T Priego ◽

AI Martin ◽

...

Keyword(s):

Gene Expression ◽

Body Weight Gain ◽

Chronic Arthritis ◽

Mrna Levels ◽

Gh Receptor ◽

Igf I ◽

Male Wistar Rats ◽

Design And Methods ◽

I Gene ◽

Gh Resistance

OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS- than in saline-treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.

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Rosa rugosa Attenuates Diabetic Oxidative Stress in Rats with Streptozotocin-Induced Diabetes

The American Journal of Chinese Medicine ◽

10.1142/s0192415x04002132 ◽

2004 ◽

Vol 32 (04) ◽

pp. 487-496 ◽

Cited By ~ 13

Author(s):

Eun Ju Cho ◽

Takako Yokozawa ◽

Hyun Young Kim ◽

Naotoshi Shibahara ◽

Jong Cheol Park

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Body Weight Gain ◽

Thiobarbituric Acid ◽

Serum Levels ◽

Serum Glucose ◽

Diabetic Rats ◽

Radical Scavenger ◽

Thiobarbituric Acid Reactive Substance ◽

Rosa Rugosa

The effects of Rosa rugosa on diabetic oxidative stress were investigated using rats with streptozotocin (STZ)-induced diabetes. The diabetic rats showed less body weight gain and heavier kidney and liver weights than normal rats, while the oral administration of Rosa rugosa at a dose of 100 or 200 mg/kg body weight/day for 20 days attenuated the physiological changes induced by diabetes. In addition, administrating Rosa rugosa to diabetic rats resulted in significant and dose-dependent decreases in the serum glucose and glycosylated protein levels, implying that Rosa rugosa improves the abnormal glucose metabolism that leads to oxidative stress. Diabetic rats had higher serum levels of superoxide and nitrite/nitrate. However, the administration of Rosa rugosa dose-dependently reduced the over-production of radicals associated with diabetes, suggesting Rosa rugosa is a radical scavenger that would play a crucial role in protecting against diabetic oxidative stress. Rosa rugosa significantly and dose-dependently reduced thiobarbituric acid-reactive substance levels in serum, hepatic and renal mitochondria, implying that Rosa rugosa would alleviate the oxidative stress associated with diabetes by inhibiting lipid peroxidation. This study provides evidence that Rosa rugosa has potential as a treatment for diabetes through attenuating oxidative stress induced by the diabetic condition

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Metabolic Syndrome Is Reduced in C57BL/6J Mice Fed High-Fat Diets Supplemented with Oak Tannins

Current Developments in Nutrition ◽

10.1093/cdn/nzaa033 ◽

2020 ◽

Vol 4 (4) ◽

Author(s):

Ting Luo ◽

Tedd Goldfinger ◽

Neil Shay

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

Weight Gain ◽

Lipid Accumulation ◽

Body Weight Gain ◽

Mrna Levels ◽

High Fat ◽

Glutathione S Transferase ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

ABSTRACT Background Wine aged in oak barrels will incorporate polyphenols inherent in the staves, suggesting that wine stored in these wooden containers will introduce oak compounds into the human body after consumption. Objective The purpose of the present study is to test whether consumption of these oak compounds could favorably influence metabolism in mice fed an obesogenic diet. Methods C57BL/6 male mice (n = 8) were fed diets for 10 wk as follows: low-fat (LF), high-fat (HF), and HF containing 0.17% of oak tannin (HF+OT). A second 10-wk study was completed; mice were provided LF, HF, and HF diets supplemented with 7.0% of concentrates made from oaked wine (HF+OWC) or unoaked wine (HF+UWC). Physiological parameters were measured during the feeding trial and serum markers and hepatic gene expression measured from samples obtained at necropsy. Results Intake of HF+OT significantly reduced body-weight gain (18.4 ± 1.2 g in HF vs. 13.2 ± 1.4 g in HF+OT, P < 0.05). Serum resistin concentrations were lower in HF+OT mice compared with HF mice (301 ± 10.1 pg/mL in HF+OT vs. 374 ± 10.9 pg/mL in HF; P < 0.05). Hepatic lipid accumulation and expression of glutathione-S-transferase-m2 (Gstm2) and NAD(P)H:quinone oxidoreductase (Nqo1) mRNAs were significantly decreased in HF+OT compared with HF mice (P < 0.05). When compared with HF-fed mice, intake of both OWC and UWC decreased body-weight gain (P < 0.05), with no significant impact on food consumption. Fasting glucose concentrations, serum insulin, and hepatic lipid accumulation were reduced in HF+OWC-fed mice compared with HF+UWC-fed mice (P < 0.05). Furthermore, hepatic glutathione-S-transferase-a1 (Gsta1) mRNA levels were significantly reduced in OWC-supplemented (0.25 ± 0.08) compared with UWC-supplemented (1.71 ± 0.24) mice (P < 0.05). Conclusions In this mouse model of metabolic disease, intake of OTs and a concentrate made from an oaked wine had a potent impact on alleviating HF-induced metabolic syndrome. Thus, intake of OTs, provided passively in oaked wine or as a dietary supplement, may act as an agent to attenuate the markers of metabolic syndrome.

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Hydrolyzed Yeast Supplementation in Calf Starter Promotes Innate Immune Responses in Holstein Calves under Weaning Stress Condition

Animals ◽

10.3390/ani10091468 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1468

Author(s):

Eun Tae Kim ◽

Hyo Gun Lee ◽

Dong Hyeon Kim ◽

Jun Kyu Son ◽

Byeong-Woo Kim ◽

...

Keyword(s):

Stress Responses ◽

Acute Phase Proteins ◽

Body Weight Gain ◽

Serum Levels ◽

Feed Additives ◽

Control Group ◽

Amyloid A ◽

Control Calf ◽

Holstein Calves ◽

Factor Α

Weaned calves are susceptible to infectious diseases because of the stress and malnutrition that occurs during weaning. Therefore, the dairy industry requires effective feed additives to ameliorate stress responses and promote immunity. This study aimed to investigate the effects of hydrolyzed yeast (HY) supplementation on the growth performance, immune and stress parameters, and health status of calves after weaning. Eighteen Holstein calves were randomly assigned to two groups, either receiving a control calf starter or 0.2% HY calf starter from one week of age. All calves were weaned at six weeks of age as a stress challenge. The HY-fed calves had a significantly-higher body weight gain during the post-weaning period (kg/week) compared to the control. Cortisol levels at three days post-weaning (DPW) were significantly lower in the HY group than the control group. Calves fed HY had significantly-higher serum levels of tumor necrosis factor-α and interleukin-1β at one DPW. The HY-fed calves also had higher concentrations of the acute-phase proteins, haptoglobin, serum amyloid A, and transferrin at one DPW. In addition, the diarrhea severity in HY-fed calves was milder after weaning compared to the control group. Our results indicate that HY supplementation reduces stress responses and may promote innate immunity in newly-weaned calves.

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Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients

Brain Sciences ◽

10.3390/brainsci9120332 ◽

2019 ◽

Vol 9 (12) ◽

pp. 332 ◽

Cited By ~ 2

Author(s):

Yasmeen M. Taalab ◽

Wessam Fathi Mohammed ◽

Manar A. Helmy ◽

Alyaa A.A. Othman ◽

Mohamed Darwish ◽

...

Keyword(s):

Gene Expression ◽

Serum Levels ◽

High Serum ◽

Cannabis Use ◽

University Hospital ◽

Mrna Levels ◽

Tnf Α ◽

Epileptic Patients ◽

Inflammatory State ◽

Factor Α

The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment. We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis. The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients. Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels. Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.

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Ameliorative effect of quercetin, catechin, and taxifolin on rotenone-induced testicular and splenic weight gain and oxidative stress in rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2018-0230 ◽

2020 ◽

Vol 31 (3) ◽

Cited By ~ 3

Author(s):

Afolabi C. Akinmoladun ◽

Oluwabunmi O. Olaniyan ◽

Courage D. Famusiwa ◽

Sunday S. Josiah ◽

M. Tolulope Olaleye

Keyword(s):

Oxidative Stress ◽

Weight Gain ◽

Molecular Mechanisms ◽

Glutathione Transferase ◽

Tissue Injury ◽

Body Weight Gain ◽

Post Treatment ◽

Reduced Body ◽

Ameliorative Effect ◽

Male Wistar Rats

AbstractBackgroundThe physiological functions of the testis and spleen can be affected through several cellular and molecular mechanisms such as the generation of reactive oxygen species (ROS) that causes oxidative stress. This study aimed at investigating the protective effect of catechin, quercetin, and taxifolin in rotenone-induced testicular and splenetic toxicity.MethodsMale Wistar rats were administered with 1.5 mg/kg rotenone (s.c.) for 10 days followed by post-treatment with catechin (5, 10, or 20 mg/kg), quercetin (5, 10, or 20 mg/kg), and taxifolin (0.25, 0.5, or 1.0 mg/kg) for 3 days (s.c.), followed by estimation of biochemical markers of oxidative stress, inflammatory activities, and tissue damage in testes and spleen.ResultsExposure of rats to rotenone caused reduced body weight gain, increased organ weight, decreased glutathione level and activities of glutathione transferase and superoxide dismutase, enhanced lipid peroxidation, and increased activities of prooxidant/proinflammatory enzymes and lactate dehydrogenase, which were mitigated by post-treatment with flavonoids. In general, quercetin and taxifolin showed better activity than catechin.ConclusionsCatechin, quercetin, and taxifolin ameliorated rotenone-induced weight disturbances and oxidative damage in rats, indicating their potential relevance in toxicant and pesticide-induced tissue injury.

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Obesity-prone high-fat-fed rats reduce caloric intake and adiposity and gain more fat-free mass when allowed to self-select protein from carbohydrate:fat intake

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00391.2015 ◽

2016 ◽

Vol 310 (11) ◽

pp. R1169-R1176 ◽

Cited By ~ 10

Author(s):

Dalila Azzout-Marniche ◽

Tristan Chalvon-Demersay ◽

Grégory Pimentel ◽

Catherine Chaumontet ◽

Nachiket A. Nadkarni ◽

...

Keyword(s):

Adipose Tissue ◽

Protein Intake ◽

Body Weight Gain ◽

Caloric Intake ◽

Fat Free Mass ◽

Mrna Levels ◽

Fat Intake ◽

High Fat ◽

Genes Encoding ◽

Male Wistar Rats

We tested the hypothesis that, for rats fed a high-fat diet (HFD), a prioritization of maintaining protein intake may increase energy consumption and hence result in obesity, particularly for individuals prone to obesity (“fat sensitive,” FS, vs. “fat resistant,” FR). Male Wistar rats ( n = 80) first received 3 wk of HFD (protein 15%, fat 42%, carbohydrate 42%), under which they were characterized as being FS ( n = 18) or FR ( n = 20) based on body weight gain. They then continued on the same HFD but in which protein (100%) was available separately from the carbohydrate:fat (50:50%) mixture. Under this second regimen, all rats maintained their previous protein intake, whereas intake of fat and carbohydrate was reduced by 50%. This increased protein intake to 26% and decreased fat intake to 37%. Adiposity gain was prevented in both FR and FS rats, and gain in fat-free mass was increased only in FS rats. At the end of the study, the rats were killed 2 h after ingestion of a protein meal, and their tissues and organs were collected for analysis of body composition and measurement of mRNA levels in the liver, adipose tissue, arcuate nucleus, and nucleus accumbens. FS rats had a higher expression of genes encoding enzymes involved in lipogenesis in the liver and white adipose tissue. These results show that FS rats strongly reduced food intake and adiposity gain through macronutrient selection, despite maintenance of a relatively high-fat intake and overexpression of genes favoring lipogenesis.

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