Vinpocetine attenuates thioacetamide-induced liver fibrosis in rats

Liver fibrosis is associated with increased mortality and morbidity. However, there is not effective treatment so far. Vinpocetine (Vinpo) is a synthetic derivative of vinca alkaloid vincamine. Limited previous reports have shown some beneficial effects of Vinpo in different organ fibrosis, but the ability of Vinpo to inhibit liver fibrosis induced by thioacetamide (TAA) has not been reported, that is why we investigate the potential ability of this vinca alkaloid derivative to attenuate liver fibrosis. Hepatic fibrosis was induced in male Sprague Dawley rats by TAA (200 mg/kg; ip; 3 times/week) for 6 weeks. Daily treatments with Vinpo (10–20 mg/kg/day; orally) ameliorated TAA-induced hepatic oxidative stress and histopathological damage as indicated by a decrease in liver injury markers, LDH, hepatic MDA, and NOx levels, as well as increase anti-oxidative parameters. Besides, the anti-fibrotic efficacy of Vinpo was confirmed by decreasing hydroxyproline, and α-SMA. Also, the anti-inflammatory effect of Vinpo was explored by decreasing IL-6 and TNF-α levels. Our novel findings were that Vinpo decreased VEGF/Ki-67 expression in the liver confirming its effect on angiogenesis and proliferation. These findings reveal the anti-fibrotic effect of Vinpo against TAA-induced liver fibrosis in rats, and suggest the modulation of oxidative stress, inflammation, angiogenesis and proliferation as mechanistic cassette underlines this effect.

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Seoritae Extract Reduces Prostate Weight and Suppresses Prostate Cell Proliferation in a Rat Model of Benign Prostate Hyperplasia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/475876 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Hoon Jang ◽

Woong-Jin Bae ◽

Seung-Mo Yuk ◽

Dong-Seok Han ◽

U-Syn Ha ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Reductase Activity ◽

Sprague Dawley ◽

Prostate Hyperplasia ◽

Prostate Cell ◽

Beneficial Effects ◽

Prostate Weight ◽

Sprague Dawley Rats ◽

Health Promoting

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.

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Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0205 ◽

2019 ◽

Vol 44 (2) ◽

pp. 153-163 ◽

Cited By ~ 7

Author(s):

Zeynep Banu Doğanlar ◽

Metehan Uzun ◽

Mehmet Akif Ovali ◽

Ayten Dogan ◽

Gulin Ongoren ◽

...

Keyword(s):

Oxidative Stress ◽

Thoracic Aorta ◽

Essential Element ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Melatonin Administration ◽

Tnf Α ◽

Element Balance ◽

Extrinsic Apoptosis ◽

Genomic Template

The aim of this study was to explain the possible mechanisms by which melatonin deficiency results in cardiovascular injury and to investigate the effects of melatonin administration on important signalling pathways and element equilibrium in the thoracic aorta (TA). For this purpose, we analysed the cellular and molecular effects of melatonin deficiency or administration on oxidative stress, DNA damage, molecular chaperone response, and apoptosis induction in TA tissues of pinealectomised rats using ELISA, RAPD, qRT-PCR, and Western blot assays. The results showed that melatonin deficiency led to an imbalance in essential element levels, unfolded or misfolded proteins, increased lipid peroxidation, and selectively induced caspase-dependent apoptosis in TA tissues without significantly affecting the Bcl-2/BAX ratio (2.28 in pinealectomised rats, 2.73 in pinealectomised rats treated with melatonin). In pinealectomised rats, the genomic template stability (80.22%) was disrupted by the significantly increased oxidative stress, and heat shock protein 70 (20.96-fold), TNF-α (1.73-fold), caspase-8 (2.03-fold), and caspase-3 (2.87-fold) were markedly overexpressed compared with the sham group. Melatonin treatment was protective against apoptosis and inhibited oxidative damage. In addition, melatonin increased the survivin level and improved the regulation of element equilibrium in TA tissues. The results of the study indicate that melatonin deficiency induces TNF-α-related extrinsic apoptosis signals and that the administration of pharmacological doses of melatonin attenuates cardiovascular toxicity by regulating the increase in the rate of apoptosis caused by melatonin deficiency in TA tissue of Sprague–Dawley rats.

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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/v3 ◽

2020 ◽

Author(s):

Jie Guo ◽

Xiaolu Cao ◽

Xianmin Hu ◽

Shulan Li ◽

Jun Wang

Keyword(s):

Oxidative Stress ◽

Terminal Deoxynucleotidyl Transferase ◽

Tunel Staining ◽

Apoptotic Cells ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Abstract Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a 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 the cerebral homogenates were detected using ELISA assay.Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group.Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

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Maresin-1 Prevents Liver Fibrosis by Targeting Nrf2 and NF-κB, Reducing Oxidative Stress and Inflammation

Cells ◽

10.3390/cells10123406 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3406

Author(s):

María José Rodríguez ◽

Matías Sabaj ◽

Gerardo Tolosa ◽

Francisca Herrera Vielma ◽

María José Zúñiga ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Fibrosis ◽

Activity Index ◽

Antioxidant Response ◽

Treated Group ◽

Hepatocyte Proliferation ◽

Sprague Dawley ◽

Ki 67 ◽

Maresin 1 ◽

Anti Inflammatory

Liver fibrosis is a complex process characterized by the excessive accumulation of extracellular matrix (ECM) and an alteration in liver architecture, as a result of most types of chronic liver diseases such as cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Maresin-1 (MaR1) is derivative of ω-3 docosahexaenoic acid (DHA), which has been shown to have pro-resolutive and anti-inflammatory effects. We tested the hypothesis that the application of MaR1 could prevent the development of fibrosis in an animal model of chronic hepatic damage. Sprague-Dawley rats were induced with liver fibrosis by injections of diethylnitrosamine (DEN) and treated with or without MaR1 for four weeks. In the MaR1-treated animals, levels of AST and ALT were normalized in comparison with DEN alone, the hepatic architecture was improved, and inflammation and necrotic areas were reduced. Cell proliferation, assessed by the mitotic activity index and the expression of Ki-67, was increased in the MaR1-treated group. MaR1 attenuated liver fibrosis and oxidative stress was induced by DEN. Plasma levels of the pro-inflammatory mediators TNF-α and IL-1β were reduced in MaR1-treated animals, whereas the levels of IL-10, an anti-inflammatory cytokine, increased. Interestingly, MaR1 inhibited the translocation of the p65 subunit of NF-κB, while increasing the activation of Nrf2, a key regulator of the antioxidant response. Finally, MaR1 treatment reduced the levels of the pro-fibrotic mediator TGF-β and its receptor, while normalizing the hepatic levels of IGF-1, a proliferative agent. Taken together, these results suggest that MaR1 improves the parameters of DEN-induced liver fibrosis, activating hepatocyte proliferation and decreasing oxidative stress and inflammation. These results open the possibility of MaR1 as a potential therapeutic agent in fibrosis and other liver pathologies.

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Abstract 400: A Nonpeptide Angiotensin (Ang) II Type 2 Receptor (AT2R) Agonist Improves Diabetic Nephropathy via Inhibition of Renal Inflammation

Hypertension ◽

10.1161/hyp.60.suppl_1.a400 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Luis Matavelli ◽

Helmy M Siragy

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Inflammatory Factors ◽

Sprague Dawley ◽

Renal Inflammation ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Compound 21 ◽

Factor Α

We explored the hypothesis that direct AT2R stimulation improves albuminuria in diabetes by reducing renal inflammation and improving oxidative stress. Sham and DM Sprague-Dawley rats were treated for 4 weeks with vehicle (V) or AT2R agonist Compound 21 (C21; 0.3 mg/kg/d). C21 was infused systemically by osmotic minipump. Diabetes was induced by streptozotocin (65 mg/kg IP). At the end of study, we monitored BP, 24h urine collection for measurements of urinary albumin to creatinine ratio (UACR), and renal interstitial fluid (RIF) levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), cGMP, and 8-isoprostane (ISO). Data are shown as mean±SE. There were no significant differences in BP between different treatments. UACR (μg/mg), compared to Control+V (14±2), increased significantly in DM+V (60±3, p<0.001) and did not change in Control+C21 (16±2). Compared to DM+V, UACR decreased significantly by 20% in DM+C21 (50±3, P<0.04). RIF TNF-α and IL-6 (pg/min), compared to Control+V (0.040±0.001 and 0.613±0.012, respectively), increased in DM+V (0.046±0.001 and 0.652±0.005, P<0.01) and did not change in Control+C21 (0.041±0.001 and 0.622±0.008). Compared to DM+V, RIF TNF-α and IL-6 decreased in DM+C21 (0.041±0.001 and 0.616±0.007, P<0.01). RIF NO (μmol/min) and cGMP (fmol/min), compared to Control+V (7.0±0.3 and 3.8±0.4), decreased in DM+V (4.3±0.5 and 1.7±0.2, P<0.001) and did not change in Control+C21 (6.6±0.3 and 3.7±0.5). RIF NO and cGMP increased in DM+C21 (6.2±0.8 and 2.7±0.4, P<0.04) compared to DM+V. RIF ISO (pmol/min), compared to Control+V (0.135±0.005), increased in DM+V (0.158±0.007, P<0.02) and did not change in Control+C21 (0.134±0.010). Compared to DM+V, RIF ISO significantly decreased in DM+C21 (0.135±0.006, P<0.03). We concluded that direct AT2R stimulation by the nonpeptide agonist C21 improves diabetic nephropathy through the reduction of renal inflammatory factors and improvement of oxidative stress.

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MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis following renal ischemia-reperfusion

AJP Renal Physiology ◽

10.1152/ajprenal.90533.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. F266-F276 ◽

Cited By ~ 43

Author(s):

Huan Ling Liang ◽

Gail Hilton ◽

Jordan Mortensen ◽

Kevin Regner ◽

Christopher P. Johnson ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Tubular Epithelial Cell ◽

Renal Ischemia ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

A Cell

Oxidative stress and apoptosis are important factors in the etiology of renal ischemia-reperfusion (I/R) injury. The present study tested the hypothesis that the cell-permeant SOD mimetic manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) protects the kidney from I/R-mediated oxidative stress and apoptosis in vivo. Male Sprague-Dawley rats (175–220 g) underwent renal I/R by bilateral clamping of the renal arteries for 45 min followed by reperfusion for 24 h. To examine the role of reactive oxygen species (ROS) in renal I/R injury, a subset of animals were treated with either saline vehicle (I/R Veh) or MnTMPyP (I/R Mn) (5 mg/kg ip) 30 min before and 6 h after surgery. MnTMPyP significantly attenuated the I/R-mediated increase in serum creatinine levels and decreased tubular epithelial cell damage following I/R. MnTMPyP also decreased TNF-α levels, gp91phox, and lipid peroxidation after I/R. Furthermore, MnTMPyP inhibited the I/R-mediated increase in apoptosis and caspase-3 activation. Interestingly, although MnTMPyP did not increase expression of the antiapoptotic protein Bcl-2, it decreased the expression of the proapoptotic genes Bax and FasL. These results suggest that MnTMPyP is effective in reducing apoptosis associated with renal I/R injury and that multiple signaling mechanisms are involved in ROS-mediated cell death following renal I/R injury.

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Administration of probiotic lactobacillus rhamnosus GG together with celecoxib attenuates oxidative stress and modulates colonic morphology in 1,2-dimethylhydrazine-induced colon cancer in sprague dawley rats

International Journal of Pharma and Bio Sciences ◽

10.22376/ijpbs.2018.9.4.b197-205 ◽

2018 ◽

Vol 9 (4) ◽

Cited By ~ 1

Author(s):

LEILA KAEID SHARAF ◽

MRIDUL SHARMA ◽

GEETA SHUKLA

Keyword(s):

Oxidative Stress ◽

Colon Cancer ◽

Lactobacillus Rhamnosus ◽

Sprague Dawley ◽

Lactobacillus Rhamnosus Gg ◽

Sprague Dawley Rats ◽

Probiotic Lactobacillus

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Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

Molecules ◽

10.3390/molecules26113442 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3442

Author(s):

Yaowared Chulikhit ◽

Wichitsak Sukhano ◽

Supawadee Daodee ◽

Waraporn Putalun ◽

Rakvajee Wongpradit ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Morris Water Maze Test ◽

Object Recognition Test ◽

Pueraria Mirifica ◽

Beneficial Effects ◽

Maze Test ◽

Y Maze ◽

Tnf Α ◽

17Β Estradiol

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

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