Bevacizumab Allows Preservation of Liver Function and its Regenerative Capacity after Major Hepatectomy

2019 ◽  
Vol 19 (11) ◽  
pp. 1388-1398
Author(s):  
Amparo Valverde ◽  
Rubén Ciria ◽  
Javier Caballero-Villarraso ◽  
Patricia Aguilar-Melero ◽  
Gustavo Ferrín ◽  
...  

Background: Parallel to the safety of liver resections, new chemotherapy drugs have emerged for the control of liver metastases. However, there is unclear evidence about the combination of intensive BVZ-therapy and extended resections. The main aim was to analyse the impact of Bevacizumab (BVZ) in terms of liver safety and tolerability in two experimental models: a basal-toxicity situation and after major hepatectomy. Methods: Eighty male-Wistar rats were grouped as toxicity analysis (sham-operated rats-OS-) and regenerationafter- surgery analysis (hepatectomy rats-H-). Eight further subgroups were created according to sacrifice (6- hours-6h- or 24-hours-24h-) and dose (μg) of BVZ (none, 100, 200, 400). Several measurements were performed, including biochemical serum samples, histopathological analysis, cytokines (IL-6, TNF-α, TGF-β), oxidative-stress (GSH/GSSG, ATP), lipid-peroxidation (TBARS) and epidermal and vascular endothelium growth-factors (EGF and VEGF). Results: In the toxicity analysis, safe results with BVZ were observed, with no significant differences among the groups. A trend towards a lower oxidative status was observed in the OS 6 h-100, -200 and -400 versus the OS 6 h-none group. Similar results were observed in the hepatectomy model, with stable oxidative-stress-index and IL-6, TNF- α, and TGF- β levels. Despite higher lipid peroxidation status, overall regeneration was preserved. As expected, VEGF was almost undetectable in BVZ-treated groups after resection, but not in the non-resection group. Conclusion: It was concluded that liver status was not impaired by BVZ even at the high-dose. Similarly, liver regeneration after extended hepatectomy in BVZ-treated animals was well-preserved. Extended liver resections may be encouraged in BVZ-treated patients due to its excellent tolerability and good liver regeneration status.

2021 ◽  
Vol 82 (1) ◽  
Author(s):  
Sidra Perveen ◽  
Shalu Kumari ◽  
Himali Raj ◽  
Shahla Yasmin

Abstract Background Fluoride may induce oxidative stress and apoptosis. It may also lead to neurobehavioural defects including neuromuscular damage. The present study aimed to explore the effects of sub lethal concentrations of sodium fluoride (NaF) on the lifespan and climbing ability of Drosophila melanogaster. In total, 0.6 mg/L and 0.8 mg/L of NaF were selected as sublethal concentrations of NaF for the study. Lifespan was measured and climbing activity assay was performed. Results The study showed significant decrease in lifespan of flies treated with fluoride. With increasing age, significant reduction in climbing activity was observed in flies treated with sodium fluoride as compared to normal (control) flies. Flies treated with tulsi (Ocimum sanctum) and NaF showed increase in lifespan and climbing activity as compared to those treated with NaF only. Lipid peroxidation assay showed significant increase in malondialdehyde (MDA) values in the flies treated with NaF as compared to control. The MDA values decreased significantly in flies treated with tulsi mixed with NaF. Conclusions The results indicate that exposure to sub lethal concentration of NaF may cause oxidative stress and affect the lifespan and climbing activity of D. melanogaster. Tulsi extract may help in reducing the impact of oxidative stress and toxicity caused by NaF.


2016 ◽  
pp. 75-78
Author(s):  
Liliia Babynets ◽  
Tetiana Maevska

The study proved that patients with combined progress of osteoarthritis and chronic pancreatitis have reliable top-level activation of lipid peroxidation in terms of malonyc aldehyde and tissue destruction in terms of oxyproline, weakening of the antioxidant level (in terms of superoxide dismutase and SH-groups) and activation parameters of catalase and ceruloplasmin (p<0,05). The authentic predictority of patients biological age, duration of combined clinical courses, the functional capacity of the pancreas in terms of fecal α-elastase, structural state by ultrasound criteria for progression effects of oxidative stress, accumulation oxyproline activation parameters catalase and ceruloplasmin, which statistically was reflected by the presence of mainly moderate of significant correlations between these groups of indicators have been identified.


Poljoprivreda ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 15-24
Author(s):  
Magdalena Matić ◽  
◽  
Rosemary Vuković ◽  
Karolina Vrandečić ◽  
Ivna Štolfa Čamagajevac ◽  
...  

During cultivation, wheat is exposed to several abiotic and/or biotic stress conditions that may adversely impact the wheat yield and quality. The impact of abiotic stress caused by nitrogen deficiency and biotic stress caused by phytopathogenic fungus Fusarium culmorum on biomarkers of oxidative stress in the flag leaf of nine winter wheat varieties (Ficko, U-1, Galloper, BC Mandica, BC Opsesija, Ingenio, Isengrain, Felix, and Bezostaya-1) was analyzed in this study. Hydrogen peroxide concentration and lipid peroxidation level were measured as indicators of oxidative stress, while the antioxidant response was determined by measuring the concentration of phenolic compounds and activities of antioxidant enzymes. Wheat variety and nitrogen treatment had a significant effect on all examined biomarkers of oxidative stress in the flag leaf, while the impact of Fusarium treatment was less pronounced. The most significant impact on the measured stress biomarkers had a low nitrogen level, which mainly increased hydrogen peroxide concentration and lipid peroxidation level and decreased activities of antioxidant enzymes in most varieties. The obtained results were discussed and compared with the previous study in which biochemical analyzes were performed on the wheat spike. There was no significant strong correlation between flag leaf and spike response in the measured parameters, which, in addition to the variety-specific response, also indicates a tissue-specific antioxidant response.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5136 ◽  
Author(s):  
Matheus Marcon ◽  
Ricieri Mocelin ◽  
Adrieli Sachett ◽  
Anna M. Siebel ◽  
Ana P. Herrmann ◽  
...  

Background The enriched environment (EE) is a laboratory housing model that emerged from efforts to minimize the impact of environmental conditions on laboratory animals. Recently, we showed that EE promoted positive effects on behavior and cortisol levels in zebrafish submitted to the unpredictable chronic stress (UCS) protocol. Here, we expanded the characterization of the effects of UCS protocol by assessing parameters of oxidative status in the zebrafish brain and reveal that EE protects against the oxidative stress induced by chronic stress. Methods Zebrafish were exposed to EE (21 or 28 days) or standard housing conditions and subjected to the UCS protocol for seven days. Oxidative stress parameters (lipid peroxidation (TBARS), reactive oxygen species (ROS) levels, non-protein thiol (NPSH) and total thiol (SH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured in brain homogenate. Results Our results revealed that UCS increased lipid peroxidation and ROS levels, while decreased NPSH levels and SOD activity, suggesting oxidative damage. EE for 28 days prevented all changes induced by the UCS protocol, and EE for 21 days prevented the alterations on NPSH levels, lipid peroxidation and ROS levels. Both EE for 21 or 28 days increased CAT activity. Discussion Our findings reinforce the idea that EE exerts neuromodulatory effects in the zebrafish brain. EE promoted positive effects as it helped maintain the redox homeostasis, which may reduce the susceptibility to stress and its oxidative impact.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hazal Tuzcu ◽  
Ibrahim Aslan ◽  
Mutay Aslan

Effect of high-dose insulin analog initiation therapy was evaluated on lipid peroxidation and oxidative stress markers in type 2 diabetes mellitus (T2DM). Twenty-four T2DM patients with HbA1c levels above 10% despite ongoing therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs. Glycemic profiles were determined over 72 hours by Continuous Glucose Monitoring System (CGMS), and blood/urine samples were collected at 24 and 72 hours. Insulin analog plus metformin treatment significantly reduced glucose variability. Plasma and urine lipid peroxidation were markedly decreased following insulin analog plus metformin treatment. No correlation existed between glucose variability and levels of plasma and urine oxidative stress markers. Likewise, changes in mean blood glucose from baseline to end point showed no significant correlation with changes in markers of oxidative stress. On the contrary, decreased levels of oxidative stress markers following treatment with insulin analogs were significantly correlated with mean blood glucose levels. In conclusion, insulin plus metformin resulted in a significant reduction in oxidative stress markers compared with oral hypoglycemic agents alone. Data from this study suggests that insulin analogs irrespective of changes in blood glucose exert inhibitory effects on free radical formation.


2005 ◽  
Vol 30 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Richard J. Simpson ◽  
Martin R. Wilson ◽  
James R. Black ◽  
James A. Ross ◽  
Greg P. Whyte ◽  
...  

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; α-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p <  0.05). TEAC and the cytokine IL-8 increased immediately after the race (p <  0.05). Plasma TNF-α remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-α response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components. Key words: acute phase response, cytokines, antioxidant capacity, creatine kinase, field study


Biologia ◽  
2006 ◽  
Vol 61 (6) ◽  
Author(s):  
Monika Ďurfinová ◽  
Marta Brechtlová ◽  
Branislav Líška ◽  
Želmíra Barošková

Abstract3′,5′-cAMP plays an important role as a second messenger molecule controlling multiple cellular processes in the brain. Its levels are decreased by phosphodiesterases (PDEs), responsible for hydrolysis of intracellular cAMP. A part of the PDE activity is dependent on the effect of calcium, mediated by its binding to calmodulin. During oxidative stress, precisely these changes in calcium concentration are responsible for cell damage. We have examined the effects of oxidative stress conditions on the activity of PDE in rat brain homogenates. We found a different influence of activated lipid peroxidation conditions (Fe2+ with ascorbate and increased temperature) on the calcium-dependent and calcium-independent PDE activity. The inhibition of Ca2+-dependent PDE was observed, while Ca2+-independent PDE was not influenced. We assume that it might be the impact of lipid peroxidation products or any mechanism activated by the higher temperature on the interaction of the Ca2+-dependent isoform of PDE with the complex calcium-calmodulin. Another explanation might be that the formation of the functioning calcium-calmodulin complex is impossible in these conditions.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 985 ◽  
Author(s):  
Abdelhafid Nani ◽  
Babar Murtaza ◽  
Amira Sayed Khan ◽  
Naim Akhtar Khan ◽  
Aziz Hichami

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.


2014 ◽  
Vol 306 (1) ◽  
pp. G37-G47 ◽  
Author(s):  
Xiang Ding ◽  
Juliane I. Beier ◽  
Keegan J. Baldauf ◽  
Jenny D. Jokinen ◽  
Hai Zhong ◽  
...  

It is known that chronic ethanol significantly impairs liver regeneration. However, the effect of acute ethanol exposure on liver regeneration remains largely unknown. To address this question, C57Bl6/J mice were exposed to acute ethanol (6 g/kg intragastrically) for 3 days, and partial hepatectomy (PHx) was performed 24 h after the last dose. Surprisingly, acute ethanol preexposure promoted liver regeneration. This effect of ethanol did not correlate with changes in expression of cell cycle regulatory genes (e.g., cyclin D1, p21, and p27) but did correlate with protection against the effect of PHx on indices of impaired lipid and carbohydrate metabolism. Ethanol preexposure protected against inhibition of the oxidant-sensitive mitochondrial enzyme, aconitase. The activity of aldehyde dehydrogenase 2 (ALDH2) was significantly increased by ethanol preexposure. The effect of ethanol was blocked by inhibiting (Daidzin) and was mimicked by activating (Alda-1) ALDH2. Lipid peroxides are also substrates for ALDH2; indeed, alcohol preexposure blunted the increase in lipid peroxidation (4OH-nonenal adducts) caused by PHx. Taken together, these data suggest that acute preoperative ethanol exposure “preconditions” the liver to respond more rapidly to regenerate after PHx by activating mitochondrial ALDH2, which prevents oxidative stress in this compartment.


2011 ◽  
Vol 300 (5) ◽  
pp. R1152-R1162 ◽  
Author(s):  
Ioanna Sigala ◽  
Panayiotis Zacharatos ◽  
Dimitris Toumpanakis ◽  
Tatiana Michailidou ◽  
Olga Noussia ◽  
...  

Inspiratory resistive breathing (IRB) induces cytokine expression in the diaphragm. The mechanism of this cytokine induction remains elusive. The roles of MAPKs and NF-κB and the impact of oxidative stress in IRB-induced cytokine upregulation in the diaphragm were studied. Wistar rats were subjected to IRB (50% of maximal inspiratory pressure) via a two-way nonrebreathing valve for 1, 3, or 6 h. Additional groups of rats subjected to IRB for 6 h were randomly assigned to receive either solvent or N-acetyl-cysteine (NAC) or inhibitors of NF-κB (BAY-11–7082), ERK1/2 (PD98059), and P38 MAPK (SB203580) to study the effect of oxidative stress, NF-κB, and MAPKs in IRB-induced cytokine upregulation in the diaphragm. Quietly breathing animals served as controls. IRB upregulated cytokine (IL-6, TNF-α, IL-10, IL-2, IL-1β) protein levels in the diaphragm and resulted in increased activation of MAPKs (P38, ERK1/2) and NF-κB. Inhibition of NF-κB and ERK1/2 blunted the upregulation of all cytokines except that of IL-6, which was further increased. P38 inhibition attenuated all cytokine (including IL-6) upregulation. Both P38 and ERK1/2 inhibition decreased NF-κB/p65 subunit phosphorylation. NAC pretreatment blunted IRB-induced cytokine upregulation in the diaphragm and resulted in decreased ERK1/2, P38, and NF-κB/p65 phosphorylation. In conclusion, IRB-induced cytokine upregulation in the diaphragm is under the regulatory control of MAPKs and NF-κB. IL-6 is regulated differently from all other cytokines through a P38-dependent and NF-κB independent pathway. Oxidative stress is a stimulus for IRB-induced cytokine upregulation in the diaphragm.


Sign in / Sign up

Export Citation Format

Share Document