Protective effects of whey on rat liver damage induced by chronic alcohol intake

2019 ◽  
Vol 38 (6) ◽  
pp. 632-645 ◽  
Author(s):  
I Radic ◽  
M Mijovic ◽  
N Tatalovic ◽  
M Mitic ◽  
V Lukic ◽  
...  

In 2012, alcohol liver disease resulted in 3.3 million—5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper–zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

2021 ◽  
pp. 8-8
Author(s):  
Ivan Radic ◽  
Mirjana Miric ◽  
Milica Mijovic ◽  
Nikola Tatalovic ◽  
Milos Mitic ◽  
...  

Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dilation, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-?B protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-?B signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.


2017 ◽  
Vol 45 (08) ◽  
pp. 1613-1629 ◽  
Author(s):  
Yan-Jiao Xu ◽  
Zao-Qin Yu ◽  
Cheng-Liang Zhang ◽  
Xi-Ping Li ◽  
Cheng-Yang Feng ◽  
...  

The present study was designed to assess the effects and potential mechanisms of ginsenosides on 17[Formula: see text]-ethynyelstradiol (EE)-induced intrahepatic cholestasis (IC). Ginsenoside at doses of 30, 100, 300[Formula: see text]mg/kg body weight was intragastrically (i.g.) given to rats for 5 days to examine the effect on EE-induced IC. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were measured. Hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined. Protein expression of proinflammatory cytokines TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] was analyzed by immunohistochemistry and Western blot. Results indicated that ginsenosides remarkably prevented EE-induced increase in the serum levels of AST, ALT, ALP and TBA. Moreover, the elevation of hepatic MDA content induced by EE was significantly reduced, while hepatic SOD activities were significantly increased when treated with ginsenosides. Histopathology of the liver tissue showed that pathological injuries were relieved after treatment with ginsenosides. In addition, treatment with ginsenosides could significantly downregulate the protein expression of TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] compared with EE group. These findings indicate that ginsenosides exert the hepatoprotective effect on EE-induced intrahepatic cholestasis in rats, and this protection might be attributed to the attenuation of oxidative stress and inflammation.


2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.


2020 ◽  
Vol 40 (8) ◽  
pp. 1854-1869
Author(s):  
Keith A. Strand ◽  
Sizhao Lu ◽  
Marie F. Mutryn ◽  
Linfeng Li ◽  
Qiong Zhou ◽  
...  

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yueqin Qiu ◽  
Jun Yang ◽  
Li Wang ◽  
Xuefen Yang ◽  
Kaiguo Gao ◽  
...  

Abstract Background Deoxynivalenol (DON) is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals. Resveratrol (RES) effectively exerts anti-inflammatory and antioxidant effects. However, the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear. Therefore, this study aimed to investigate the effect of RES on growth performance, gut health and the gut microbiota in DON-challenged piglets. A total of 64 weaned piglets [Duroc × (Landrace × Yorkshire), 21-d-old, 6.97 ± 0.10 kg body weight (BW)] were randomly allocated to 4 treatment groups (8 replicate pens per treatment, each pen containing 2 males; n = 16 per treatment) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. Results DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) mRNA and protein expression, and increased zonula occludens-1 (ZO-1) mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet (P < 0.05). Compared with unsupplemented DON-challenged piglets, infected piglets fed a diet with RES showed significantly decreased malondialdehyde (MDA) levelsand increased mRNA expression of antioxidant enzymes and antioxidant genes (i.e., GCLC, GCLM, HO-1, SOD1 and NQO-1) and glutamate-cysteine-ligase modulatory subunit (GCLM) protein expression (P < 0.05). Moreover, RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets (P < 0.05). Finally, RES supplementation significantly increased the abundance of Roseburia and butyrate concentrations, while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone (P < 0.05). Conclusions RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function, alleviating intestinal inflammation and oxidative damage, and positively modulating the gut microbiota. The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations, and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 439
Author(s):  
Naila Boby ◽  
Muhammad Aleem Abbas ◽  
Eon-Bee Lee ◽  
Zi-Eum Im ◽  
Walter H. Hsu ◽  
...  

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.


2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.


2008 ◽  
Vol 1 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Vicky Lahaie-Collins ◽  
Julie Bournival ◽  
Marilyn Plouffe ◽  
Julie Carange ◽  
Maria-Grazia Martinoli

Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP+) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP+-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP+-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP+stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP+-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.


Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.


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