6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity

Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.

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Mesenchymal Stromal Cells Suppress Hepatic Fibrosis Via Modulating the Expression of Fibronectin and Integrin and Inhibiting DNA Fragmentation in Rats

Archives of Medical Science ◽

10.5114/aoms/134826 ◽

2021 ◽

Author(s):

sherine ibrahim ◽

ahmed fayez ◽

ahmed maher

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Dna Fragmentation ◽

Inflammatory Markers ◽

Treated Group ◽

Control Group ◽

Sprague Dawley ◽

Standard Drug ◽

Anti Inflammatory ◽

Stromal Stem Cells

IntroductionLiver fibrosis is currently the 11th most common cause of death worldwide. Because of self-renewal, available sources for isolation, and high differentiation properties, multipotent mesenchymal stromal stem cells are suggested to be potential tool for treatment of liver fibrosis. In this study, we examined the anti-fibrotic and anti-inflammatory activity of bone marrow-derived multipotent mesenchymal stromal stem cells (MSCs) on liver fibrosis induced by carbon tetrachloride on rats relative to silymarin as a standard drug.Material and methodsThis study was performed on 40 male Sprague Dawley rats divided into 4 groups of ten rats each: Group 1 served as controls, Group 2 served as CCl4 (diseased) group, Group 3 served as silymarin treated group and Group 4 served as MSCs treated group. Liver fibrosis was assessed by determination of liver markers and fibrogenesis related genes together with the anti-inflammatory markers in the liver tissue. DNA fragmentation was assessed by Comet assay.ResultsMSCs treatment reduced all liver fibrosis markers as well as the oxidative stress and inflammatory markers. Additionally, MSCs reduced the expression of integrins and fibronectin compared with the control group as well as decreasing DNA fragmentation.ConclusionsTreatment by MSCs significantly ameliorates liver fibrosis in rats. This amelioration was a result of acting on both the anti-inflammatory and anti-fibrotic activity of hepatocytes.

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Protective Effects of Astaxanthin on Nephrotoxicity in Rats with Induced Renovascular Occlusion

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200914104432 ◽

2020 ◽

Vol 23 ◽

Author(s):

Erkan Arslan ◽

Hakan Turk ◽

Murat Caglayan ◽

Tugba Taskin Turkmenoglu ◽

Ataman Gonel ◽

...

Keyword(s):

Oxidative Stress ◽

Olive Oil ◽

Caspase 3 ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Control Group ◽

Tubular Damage ◽

Total Thiol ◽

Tnf Α ◽

Anti Inflammatory

Background: Various effects of Astaxanthin was shown in the studies including its antioxidant, anti-inflammatory, anti-tumor and immunregulator effects. Objective: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms. Methods: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemiareperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were performed for each group. Results: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to IRI group and close to the level of the control group (p <0.05). Caspase-3 levels of tissue samples were significantly increased in IRI group compared to other groups, but significantly lower in IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p <0.001), but still higher than the control group (p <0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in IRI + ASX group in comparison to the IRI group (p <0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p <0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in IRI group with respect to the other groups (p <0.005). Conclusion: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapopitotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.

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Bees’ Honey Attenuation of Metanil-Yellow-Induced Hepatotoxicity in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/614580 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Abdulrahman L. Al-Malki ◽

Ahmed Amir Radwan Sayed

Keyword(s):

Oxidative Stress ◽

Inflammatory Markers ◽

Histopathological Examination ◽

Fatty Degeneration ◽

Control Group ◽

Cytoplasmic Vacuolization ◽

Liver Injuries ◽

Metanil Yellow ◽

Anti Inflammatory

The present study aims to investigate the protective effect of bees’ honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200 mg/kg metanil yellow, and three groups treated with metanil yellow plus2.5 mg·kg-1·day-1bees’ honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees’ honey reduced the oxidative stress in the liver tissue and downregulated the inflammatory markers. In addition, the elevated levels of AGE and the activated NF-κB in the metanil-yellow-treated animals were significantly attenuated. Moreover, the levels of TNF-αand IL-1βwere significantly attenuated as a result of bees’ honey administration. Furthermore, the histopathological examination of the liver showed that bees’ honey reduced fatty degeneration, cytoplasmic vacuolization, and necrosis in metanil-yellow-treated rats. In conclusion, the obtained data suggest that bees’ honey has hepatoprotective effect on acute liver injuries induced by metanil-yellowin vivo, and the results suggested that the effect of bees’ honey against metanil yellow-induced liver damage is related to its antioxidant/anti-inflammatory properties which attenuate the activation of NF-κB and its controlled genes like TNF-αand IL-1β.

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Effect of caraway on gentamicin-induced oxidative stress, inflammation and nephrotoxicity in rats

Veterinary Science Development ◽

10.4081/vsd.2015.5896 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 2

Author(s):

Hoda Erjaee ◽

Fatemeh Azma ◽

Saeed Nazifi

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Group Treatment ◽

Structural Damage ◽

Seed Oil ◽

Treated Group ◽

Control Group ◽

Protective Effects ◽

Simultaneous Treatment ◽

Tnf Α

Different potentially therapeutic approaches to prevent or attenuate gentamicin (GEM) induced nephrotoxicity have been proposed. The aim of the present study was to investigate the possible protective effects of caraway seed oil against GEM-induced nephrotoxicity in rats. Rats (24) were randomly assigned into four equal groups: i) normal control group, ii) treated with GEM, iii) pretreated with orally caraway seed oil 10 (mg kg−1) plus GEM and iv) treated with GEM and caraway seed oil 10 mg kg−1. Biochemical examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, blood urea nitrogen (BUN), plasma malondialdehyde (MDA) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and BUN concentrations. The animals treated with gentamicin alone showed a significantly higher plasma MDA level andlower SOD, GSH-Px and CAT activities when compared with the control group. Treatment and simultaneous treatment with caraway seed oil produced amelioration in MDA and increased the activity of antioxidant enzymes SOD, GSH-Px and CAT when compared with the gentamicin treated group. In addition, GEM nephrotoxicity increased renal inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Pro-inflammatory cytokines were significantly decreased (P<0.05) in the test groups administered caraway seed oil. These findings suggest that caraway seed oil treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in rats.

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Olive Extract Ameliorates Oxidative Stress and Inflammation, and Protects Intestinal Villus and Microbiota in Piglets Induced by Lipopolysaccharides

10.21203/rs.3.rs-101171/v1 ◽

2020 ◽

Author(s):

Yu Zhang ◽

Zhao-Xi Deng ◽

Mao-Long He ◽

Xin M. Luo ◽

Jian-Xin Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Block Design ◽

Basal Diet ◽

Control Group ◽

Weaned Piglets ◽

Intestinal Villus ◽

Maslinic Acid ◽

Lps Challenge ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background: The olive extract contains compounds with antioxidant and anti-inflammatory properties. This study was designed to investigate whether olive cake extract, enriched with maslinic acid and hydroxytyrosol, alleviates the lipopolysaccharides (LPS)-induced oxidative stress, inflammation and intestinal villus damage in piglets.Methods: Thirty weaned piglets (6.9±0.9 kg) were assigned to five groups using a randomized complete block design. Piglets were fed a basal diet before intraperitoneal (i.p.) injection of physiological saline (C); fed a basal diet alone (CL) or fed a basal diet plus olive extract (OL), antibiotics (AL), or olive extract and antibiotics (OAL) before i.p. injection of LPS. The feeding lasted for 2 weeks. Piglets were euthanized 4h after LPS injection. Systemic anti-oxidant and inflammation levels were measured and villus morphology in the intestine was examined.Results: Compared with those in the C group, piglets in the CL group had significantly lower GSH-Px, SOD, ALB levels and higher MDA, NO, LDH, ALT and AST levels in the serum (P<0.05). Compared with the CL group, piglets in OL, AL, and OAL groups had significantly higher serum GSH-Px, SOD and ALB levels and lower MDA, NO, LDH, ALT and AST levels (P<0.05). LPS administration significantly increased the serum concentration of TNF-α, IL-6, DAO and D-xylose in the CL group compared with the control group (P<0.05). Piglets in OL, AL, and OAL groups had significantly lower serum TNF-α, IL-6, DAO and D-xylose levels and higher IL-10 level (P<0.05). In the duodenum and ileum of piglets, LPS challenge led to significantly lower villus height (VH), higher crypt depth (CD) and lower VH/CD compared with the control group (P<0.05), whereas, OL, AL, and OAL groups had significantly lower CD and higher VH/CD compared with the CL group (P<0.05). Dietary inclusion of olive extract increased the relative abundance of intestinal Lactobacillus and Clostridium at genus level.Conclusion: Dietary supplementation with olive extract maslinic acid and hydroxytyrosol improved anti-oxidative and anti-inflammatory capacity, intestinal structure morphology, and increased the abundance of beneficial intestinal bacteria in weaned piglets challenged by LPS.

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The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

10.21203/rs.2.16758/v1 ◽

2019 ◽

Author(s):

Jie Guo ◽

Xiaolu Cao ◽

Xianmin Hu ◽

Shulan Li ◽

Jun Wang

Keyword(s):

Oxidative Stress ◽

Terminal Deoxynucleotidyl Transferase ◽

Control Group ◽

Tunel Staining ◽

High Dose ◽

Sprague Dawley ◽

Curcumin Treatment ◽

Concurrent Administration ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background: As a chemical extensively used in industrial areas as well as formed during heating of carbohydrate-rich food and tobacco, acrylamide (ACR) has been known as well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cerebral homogenates were detected using ELISA assay. Results: Concurrent administration of curcumin at the oral doses of 50 and 100 mg/kg with ACR significantly protected the rats from ACR-induced weigh loss and motor function deficits, and improved the pathological alterations in the ACR-intoxicated brains. Curcumin treatment especially at a high dose enhanced the TERT mRNA expression level and increased the number of TERT-positive nerve cells in cortex tissues of ACR intoxicated rats. The levels of MDA, TNF-α and IL-1β in the cerebral homogenates were reduced, the contents of GSH as well as the activities of SOD and GSH-Px were increased by curcumin treatment, compared to ACR control group. Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. And maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

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Evaluation of anti-nociceptive, anti-inflammatory and hepatoprotective effects of methanol extract of Mazus pumilus (Burm. f.) Steenis (Mazaceae) herb

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i4.17 ◽

2021 ◽

Vol 18 (4) ◽

pp. 799-807

Author(s):

Saiqa Ishtiaq ◽

Ayesha Ilyas ◽

Numera Irshad ◽

Uzma Niaz ◽

Uzma Hanif ◽

...

Keyword(s):

Methanol Extract ◽

Inflammatory Activity ◽

Control Group ◽

Tail Flick ◽

Histopathological Analysis ◽

Standard Drug ◽

Rat Paw Edema ◽

Hepatoprotective Effects ◽

Anti Inflammatory ◽

Different Doses

Purpose: This study was designed to investigate the anti-nociceptive, anti-inflammatory and hepatoprotective activities of the methanol extract of Mazus pumilus (Mazaceae) herb. Methods: Anti-nociceptive activity was determined using hot plate, tail flick and acetic acid-induced writing methods. Carrageenan-induced rat paw edema (0.1 mL of 1 %) model was used for the assessment of anti-inflammatory activity. The methanol extract was administered orally at three different doses (150, 300 and 600 mg/kg) to three separate groups in all the experiments. Diclofenac sodium (50 mg/kg) was used as standard drug while control group received DMSO (1 %, 10 mL/kg). The hepatocurative effect of methanol extract of M. pumilus (400 mg/kg) was determined in isoniazid (50 mg/kg) and rifampicin (100 mg/kg) induced liver injury. Silymarin (100 mg/kg) was used as standard drug for comparison. The control group received distilled water (10 mL/kg). Preliminary phytochemical screening was also carried out. Results: The methanol extract of M. pumilus significantly (p < 0.05) augmented latency time and reduced the number of writhes in the pain models at all doses used for the assessment of antinociceptive actions. The anti-inflammatory activity of different doses of extract was evaluated by measuring the reduction in the size of the paw. A significant (p < 0.05) hepatocurative effect was observed when administered after anti-tuberculosis drugs. Histopathological analysis of the liver tissues also revealed restored hepatocellular architecture. Conclusion: The results demonstrate the anti-nociceptive, anti-inflammatory and hepatoprotective effects of the methanol extract of M. pumilus, thus substantiating the ethnomedical claims associated with the herb.

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Comparing the anti-inflammatory effects of Simvastatin and Rosuvastatin by measuring IL-1β, IL-6 and TNF-α levels using a murinic caecal ligation and puncture induced sepsis model / Compararea efectelor anti-inflamatoare ale Simvastatinei și Rosuvastatinei măsurând nivelele serice ale IL-1β, IL-6 si TNF-α folosind un model de sepsis la șobolan indus prin ligatură și puncție cecală

Revista Romana de Medicina de Laborator ◽

10.2478/rrlm-2014-0037 ◽

2014 ◽

Vol 22 (4) ◽

Author(s):

Mihai Mărginean M ◽

Sebastian Trancă ◽

Alina Ardelean-Maghiar (Mărginean) ◽

Dan Dîrzu ◽

Adina Huțanu ◽

...

Keyword(s):

Treated Group ◽

Untreated Group ◽

Control Group ◽

Blood Levels ◽

Cell Counts ◽

Sepsis Model ◽

Tnf Α ◽

Anti Inflammatory ◽

Caecal Ligation And Puncture ◽

Caecal Ligation

AbstractBackground: Sepsis is a systemic host response to an infection which may evolve into severe sepsis and septic shock. It raises many health care related concerns around the world, carrying almost 30% mortality rates and a high financial burden. The disease is characterized by the triggering of some inflammatory pathways that are ultimately proven deleterious to the host organism. Although antibiotics, fluid administration, vasopressor therapy and infectious source control remain the recommended management strategies, emerging scientific data proposes statins as a new line of treatment. These drugs were first introduced in clinical practice for their cholesterol-lowering effect but the inhibition of HMG-CoA reductase and cholesterol biosynthetic pathway exhibits some less studied effects generally referred to as pleiotropic: anti-inflammatory, antithrombotic, immunomodulatory and antioxidant properties. Objective: To asses and compare the anti-inflammatory effect of two statins - Simvastatin and Rosuvastatin - measuring blood levels of IL-1β, IL-6 and TNFα using a previously described murinic model of sepsis. Methods: We compiled four groups (C, n=7; SEP, SV, RV, n=8). Statins were administered in two doses 18 and 3 hours before surgical intervention. Sepsis was induced using the caecal ligation and puncture technique. Blood samples were obtained by venepuncture from each subject in day 1, 4, 7 and 14 (the last samples were obtained by cardiac puncture). Complete blood count, Procalcitonin, IL-1β, IL-6 and TNF-α levels were assessed. Results: White blood cell counts differed across the groups showing a higher count for the septic but untreated group. Procalcitonin reacted in all septic groups but both statin treated groups had lower levels when compared to untreated group. IL-1β levels were higher in the Rosuvastatin treated group. IL-6 levels were more heterogeneously dispersed but higher levels were noticed in the untreated septic group. The Simvastatin treated group had higher levels compared to the Rosuvastatin treated one. TNFα levels were higher in the septic untreated group and in the Rosuvastatin treated one. For the Simvastatin treated subjects, the level of TNFα was similar with the control group. Conclusion: We concluded that both drugs showed anti-inflammatory effects on the murinic CLP-induced sepsis model. Between the two, Simvastatin had greater impact by lowering blood levels of established pro-inflammatory markers.

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Curcumin Nanomicelle Improves Lipid Profile, Stress Oxidative Factors and Inflammatory Markers in Patients Undergoing Coronary Elective Angioplasty; A Randomized Clinical Trial

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666210104145231 ◽

2021 ◽

Vol 21 ◽

Author(s):

Bijan Helli ◽

Hadis Gerami ◽

Maria Kavianpour ◽

Habib Heybar ◽

Seyed Kianoosh Hosseini ◽

...

Keyword(s):

Oxidative Stress ◽

Clinical Trial ◽

Lipid Profile ◽

Inflammatory Markers ◽

Interleukin 1 ◽

Stress Factors ◽

Inflammatory Factors ◽

Control Group ◽

Controlled Clinical Trial ◽

Tnf Α

Background: Curcumin demonstrated many pharmacological effects including antioxidants, anti-inflammation, eliminating free radicals, anti-tumor, lipid regulation, and anti-coagulation. Objective: This study aimed to assess and compare curcumin and nano-curcumin effects on lipid profile, oxidative stress, and inflammatory factors related to patients ‘heart. Method: This randomized, double-blind, placebo-controlled clinical trial was conducted on 90 patients undergoing coronary elective angioplasty which were randomly divided into 3 groups. The doses administered for 8 weeks were a 500 mg capsule of curcumin daily for the first group and an 80 mg capsule of nano-curcumin for the second group. However, the placebo group received capsules like curcumin. Lipid profile, oxidative stress factors, and inflammatory markers were measured at the baseline and end of the experiment. Results: Statistically significant changes were observed in the total cholesterol (TC), triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) in the intervention groups to the control group (p<0.05). Curcumin and nano-curcumin supplementation also improved significant changes in plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), high-sensitivity C-reactive protein (hs-CRP), Interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in comparison to the placebo (p<0.05). Furthermore, the nano-curcumin group compared to the curcumin group demonstrated significant changes (p<0.05) in TC, TG, SOD, MDA and TNF-α levels. Conclusion: The effects of curcumin on nano formula may be better for cardiac patients due to its high bioavailability.

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Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation

International Journal of Molecular Sciences ◽

10.3390/ijms19092706 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2706 ◽

Cited By ~ 9

Author(s):

Cristina Sena ◽

Maria Cipriano ◽

Maria Botelho ◽

Raquel Seiça

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Liver Function ◽

Hepatic Steatosis ◽

Lipoic Acid ◽

High Fat Diet ◽

Control Group ◽

High Fat ◽

Tnf Α

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

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