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Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 158
Author(s):  
Raquel G. Bardallo ◽  
Idoia Company-Marin ◽  
Emma Folch-Puy ◽  
Joan Roselló-Catafau ◽  
Arnau Panisello-Rosello ◽  
...  

The need to meet the demand for transplants entails the use of steatotic livers, more vulnerable to ischemia-reperfusion (IR) injury. Therefore, finding the optimal composition of static cold storage (SCS) preservation solutions is crucial. Given that ROS regulation is a therapeutic strategy for liver IR injury, we have added increasing concentrations of PEG35 and glutathione (GSH) to the preservation solutions (IGL-1 and IGL-2) and evaluated the possible protection against energy depletion and oxidative stress. Fatty livers from obese Zücker rats were isolated and randomly distributed in the control (Sham) preserved (24 h at 4 °C) in IGL-0 (without PEG35 and 3 mmol/L GSH), IGL-1 (1 g/L PEG35, and 3 mmol/L GSH), and IGL-2 (5 g/L PEG35 and 9 mmol/L GSH). Energy metabolites (ATP and succinate) and the expression of mitochondrial oxidative phosphorylation complexes (OXPHOS) were determined. Mitochondrial carrier uncoupling protein 2 (UCP2), PTEN-induced kinase 1 (PINK1), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the inflammasome (NLRP3) expressions were analyzed. As biomarkers of oxidative stress, protein oxidation (AOPP) and carbonylation (DNP derivatives), and lipid peroxidation (malondialdehyde (MDA)–thiobarbituric acid (TBA) adducts) were measured. In addition, the reduced and oxidized glutathione (GSH and GSSG) and enzymatic (Cu–Zn superoxide dismutase (SOD), CAT, GSH S-T, GSH-Px, and GSH-R) antioxidant capacities were determined. Our results showed that the cold preservation of fatty liver graft depleted ATP, accumulated succinate and increased oxidative stress. In contrast, the preservation with IGL-2 solution maintained ATP production, decreased succinate levels and increased OXPHOS complexes I and II, UCP2, and PINK-1 expression, therefore maintaining mitochondrial integrity. IGL-2 also protected against oxidative stress by increasing Nrf2 and HO-1 expression and GSH levels. Therefore, the presence of PEG35 in storage solutions may be a valuable option as an antioxidant agent for organ preservation in clinical transplantation.


Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 153
Author(s):  
Stepan Melnyk ◽  
Reza Hakkak

Obesity is growing worldwide epidemic. Animal models can provide some clues about the etiology, development, prevention, and treatment of obesity. We examined and compared serum metabolites between seven lean (L) and seven obese (O) female Zucker rats to investigate the individual serum metabolic profile. A combination of HPLC-UV, HPLC-ECD, and LC-MS revealed more than 400 peaks. The 50 highest quality peaks were selected as the focus of our study. Untargeted metabolomics analysis showed significantly higher mean peak heights for 20 peaks in L rats, generally distributed randomly, except for a cluster (peaks 44–50) where L showed stable dominancy over O. Only eight peaks were significantly higher in O rats. Peak height ratios between pairs of L and O rats were significantly higher at 199 positions in L rats and at 123 positions in O rats. Targeted metabolomics analysis showed significantly higher levels of methionine, cysteine, tryptophan, kynurenic acid, and cysteine/cystine ratio in L rats and significantly higher levels of cystine and tyrosine in O rats. These results contribute to a better understanding of systemic metabolic perturbations in the obese Zucker rat model, emphasizing the value of both whole metabolome and individual metabolic profiles in the design and interpretation of studies using animal models.


2022 ◽  
Author(s):  
Armaghan Saeb ◽  
Sarah Maria Grundmann ◽  
Denise K Gessner ◽  
Sven Schuchardt ◽  
Erika Most ◽  
...  

an alternative and sustainable source of food and feed. A byproduct from mass-rearing of insect larvae are the shed cuticles - the most external components of insects which are a...


Author(s):  
Arsenii V Telichko ◽  
Rehman Ali ◽  
Thurston Brevett ◽  
Huaijun Wang ◽  
Jose Vilches-Moure ◽  
...  

Abstract Objective: Speed of sound has previously been demonstrated to correlate with fat concentration in the liver. However, estimating speed of sound in the liver noninvasively can be biased by the speed of sound of the tissue layers overlying the liver. Here, we demonstrate a noninvasive local speed of sound estimator, which is based on a layered media assumption, that can accurately capture the speed of sound in the liver. We validate the estimator using an obese Zucker rat model of non-alcoholic fatty liver disease and correlate the local speed of sound with liver steatosis. Approach: We estimated the local and global average speed of sound noninvasively in 4 lean Zucker rats fed a normal diet and 16 obese Zucker rats fed a high fat diet for up to 8 weeks. The ground truth speed of sound and fat concentration were measured from the excised liver using established techniques. Main Results: The noninvasive, local speed of sound estimates of the livers were similar in value to their corresponding "ground truth'' measurements, having a slope ± standard error of the regression of 0.82 ± 0.15 (R2 = 0.74 and p < 0.001). Measurement of the noninvasive global average speed of sound did not reliably capture the ``ground truth'' speed of sound in the liver, having a slope of 0.35 ± 0.07 (R2 = 0.74 and p < 0.001). Decreasing local speed of sound was observed with increasing hepatic fat accumulation (approximately -1.7 m/s per 1% increase in hepatic fat) and histopathology steatosis grading (approximately -10 to -13 m/s per unit increase in steatosis grade). Local speed of sound estimates were highly correlated with steatosis grade, having Pearson and Spearman correlation coefficients both ranging from -0.87 to -0.78. In addition, a lobe-dependent speed of sound in the liver was observed by the ex vivo measurements, with speed of sound differences of up to 25 m/s (p < 0.003) observed between lobes in the liver of the same animal. Significance: The findings of this study suggest that local speed of sound estimation has the potential to be used to predict or assist in the measurement of hepatic fat concentration and that the global average speed of sound should be avoided in hepatic fat estimation due to significant bias in the speed of sound estimate.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina M. Opyd ◽  
Adam Jurgoński

AbstractWe hypothesized that milk thistle seed or seed oil dietary supplementation reduces intestinal, liver and lipid disorders specific to genetic obesity, and the seeds can be more efficient in doing so. Lean and obese male Zucker rats were allocated to 4 groups: the lean (LC) and obese control (OC) groups fed a standard diet and the other 2 obese groups fed a diet supplemented with milk thistle seed oil (O + MTO) or milk thistle seeds (O + MTS). After 5 weeks of feeding, the cecal SCFA pool was slightly and significantly lower in OC and O + MTO compared with LC and O + MTS. The liver fat content was greater in OC, O + MTO and O + MTS compared with LC; however, it was significantly lower in O + MTS than in OC and O + MTO. The plasma cholesterol was greater in OC compared with LC, O + MTO and O + MTS; however, it was significantly greater in O + MTO and O + MTS compared with LC. The plasma bilirubin was detected in OC and O + MTO, whereas it was not present in LC and O + MTS. Milk thistle seeds can improve fermentation events in the distal intestine and reduce other disorders specific to genetically obese rats, and the seed PUFAs are responsible for that to a lesser extent.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Rodrigo Vanerson Passos Neves ◽  
Hugo de Luca Corrêa ◽  
Ivo Vieira de Sousa Neto ◽  
Michel Kendy Souza ◽  
Fernando Costa ◽  
...  

Aerobic training (AT) promotes several health benefits that may attenuate the progression of obesity associated diabetes. Since AT is an important nitric oxide (NO-) inducer mediating kidney-healthy phenotype, the present study is aimed at investigating the effects of AT on metabolic parameters, morphological, redox balance, inflammatory profile, and vasoactive peptides in the kidney of obese-diabetic Zucker rats receiving L-NAME (N(omega)-nitro-L-arginine methyl ester). Forty male Zucker rats (6 wk old) were assigned into four groups ( n = 10 , each): sedentary lean rats (CTL-Lean), sedentary obese rats (CTL-Obese), AT trained obese rats without blocking nitric oxide synthase (NOS) (Obese+AT), and obese-trained with NOS block (Obese+AT+L-NAME). AT groups ran 60 min in the maximal lactate steady state (MLSS), five days/wk/8 wk. Obese+AT rats improved glycemic homeostasis, SBP, aerobic capacity, renal mitochondria integrity, redox balance, inflammatory profile (e.g., TNF-α, CRP, IL-10, IL-4, and IL-17a), and molecules related to renal NO- metabolism (klotho/FGF23 axis, vasoactive peptides, renal histology, and reduced proteinuria). However, none of these positive outcomes were observed in CTL-Obese and Obese+AT+L-NAME ( p < 0.0001 ) groups. Although Obese+AT+L-NAME lowered BP (compared with CTL-Obese; p < 0.0001 ), renal damage was observed after AT intervention. Furthermore, AT training under conditions of low NO- concentration increased signaling pathways associated with ACE-2/ANG1-7/MASr. We conclude that AT represents an important nonpharmacological intervention to improve kidney function in obese Zucker rats. However, these renal and metabolic benefits promoted by AT are dependent on NO- bioavailability and its underlying regulatory mechanisms.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2528
Author(s):  
Ilenia Martinelli ◽  
Daniele Tomassoni ◽  
Proshanta Roy ◽  
Francesco Amenta ◽  
Seyed Khosrow Tayebati

The association between obesity and loss of cognitive performance has been recognized. Although there are data regarding the metabolic alterations in obese conditions and the development of neuroinflammation, no clear evidence concerning obesity-related cholinergic and synaptic impairments in the frontal cortex and hippocampus has been reported yet. Here, we investigate different cholinergic and synaptic markers in 12-, 16-, and 20-week-old obese Zucker rats (OZRs) compared with lean littermate rats (LZRs), using immunochemical and immunohistochemical analysis. Consequently, OZRs showed body weight gain, hypertension, and dysmetabolism. In 20-week-old OZRs, the reduction of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptors (α7nAChR) occurred both in the frontal cortex and in the hippocampus, suggesting a cognitive dysfunction due to obesity and aging. Among the muscarinic receptors analyzed, the level of expression of type 1 (mAChR1) was lower in the hippocampus of the older OZRs. Finally, we showed synaptic dysfunctions in OZRs, with a reduction of synaptophysin (SYP) and synaptic vesicle glycoprotein 2B (SV2B) in 20-week-old OZRs, both in the frontal cortex and in the hippocampus. Taken together, our data suggest specific alterations of cholinergic and synaptic markers that can be targeted to prevent cognitive deficits related to obesity and aging.


2021 ◽  
Vol 22 (16) ◽  
pp. 8542
Author(s):  
Njikem Asong-Fontem ◽  
Arnau Panisello-Rosello ◽  
Alexandre Lopez ◽  
Katsunori Imai ◽  
Franck Zal ◽  
...  

The combined impact of an increasing demand for liver transplantation and a growing incidence of nonalcoholic liver disease has provided the impetus for the development of innovative strategies to preserve steatotic livers. A natural oxygen carrier, HEMO2life®, which contains M101 that is extracted from a marine invertebrate, has been used for static cold storage (SCS) and has shown superior results in organ preservation. A total of 36 livers were procured from obese Zucker rats and randomly divided into three groups, i.e., control, SCS-24H and SCS-24H + M101 (M101 at 1 g/L), mimicking the gold standard of organ preservation. Ex situ machine perfusion for 2 h was used to evaluate the quality of the livers. Perfusates were sampled for functional assessment, biochemical analysis and subsequent biopsies were performed for assessment of ischemia-reperfusion markers. Transaminases, GDH and lactate levels at the end of reperfusion were significantly lower in the group preserved with M101 (p < 0.05). Protection from reactive oxygen species (low MDA and higher production of NO2-NO3) and less inflammation (HMGB1) were also observed in this group (p < 0.05). Bcl-1 and caspase-3 were higher in the SCS-24H group (p < 0.05) and presented more histological damage than those preserved with HEMO2life®. These data demonstrate, for the first time, that the addition of HEMO2life® to the preservation solution significantly protects steatotic livers during SCS by decreasing reperfusion injury and improving graft function.


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