scholarly journals Induced Short-term Hearing Loss due to Stimulation of Age-related Factors by Intermittent Hypoxia, High-Fat Diet, and Galactose Injection

2020 ◽  
Author(s):  
Dong Jun Park ◽  
Sunmok Ha ◽  
Jin Sil Choi ◽  
Su Hoon Lee ◽  
Jeong-Eun Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Cellular Aging ◽  
High Fat ◽  
Short Term ◽  
Related Factors ◽  
Age Related

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. It is associated with aging and hair cell death due to oxidative stress-induced mitochondrial dysfunction. Although transgenic mice and long-term cultures for induction of aging have been used to study ARHL, there are presently no ARHL animal models stimulated by intermittent environmental change for aging. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined based on the expression of the hearing loss-induced phenotype and aging related factors in the short term. The incidence of hearing loss was significantly different among the groups subjected to intermittent hypoxic environment, high-fat diet (HFD), and injection with D-galactose. Continuous oxidative stress and HFD were factors that accelerated cellular aging. Increase in UCP2 affected oxidative stress and mitochondrial dysfunction. CDH23, SLC26A4, KCNQ4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in cells of the hearing organ. We found that intermittent hypoxic, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects intermittent environmental changes, will benefit future research on ARHL.

scholarly journals Induced Short-Term Hearing Loss due to Stimulation of Age-Related Factors by Intermittent Hypoxia, High-Fat Diet, and Galactose Injection

2020 ◽  
Vol 21 (19) ◽  
pp. 7068
Author(s):  
Dong Jun Park ◽  
Sunmok Ha ◽  
Jin Sil Choi ◽  
Su Hoon Lee ◽  
Jeong-Eun Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
High Fat Diet ◽  
Intermittent Hypoxia ◽  
Environmental Changes ◽  
Cellular Aging ◽  
High Fat ◽  
Short Term ◽  
Related Factors ◽  
Age Related

Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in Ucp2, usually expressed during mitochondrial dysfunction, was observed. Expression of Cdh23, Slc26a4, Kcnq4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.

Hyperbaric oxygen therapy attenuates D-galactose-induced-age-related cardiac dysfunction through mitigating cardiac mitochondrial dysfunction in pre-diabetic rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bo-Htay ◽  
T Shwe ◽  
S Palee ◽  
T Pattarasakulchai ◽  
K Shinlapawittayatorn ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Normal Diet ◽  
Lv Function ◽  
High Fat ◽  
Insulin Resistant ◽  
Lv Dysfunction ◽  
Age Related ◽  
Mitochondrial Functions

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants

scholarly journals Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Locomotor Activity ◽  
Substantia Nigra ◽  
High Fat Diet ◽  
Model Assessment ◽  
High Fat

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.

scholarly journals Curcumin Inhibits Age-Related Vascular Changes in Aged Mice Fed a High-Fat Diet

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1476 ◽  
Author(s):  
Kenichiro Takano ◽  
Junko Tatebe ◽  
Naohiro Washizawa ◽  
Toshisuke Morita
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Heme Oxygenase 1 ◽  
Vascular Aging ◽  
High Fat ◽  
Sirt1 Expression ◽  
Age Related ◽  
Westernized Diet ◽  
Term Administration ◽  
Oxidative Effects

Inhibiting the onset of arteriosclerotic disease, which has been increasing due to the westernized diet and aging, is a significant social challenge. Curcumin, a type of polyphenol, has anti-oxidative effects and anti-inflammatory action and is expected to treat and to have prophylactic effects on different diseases. In this study, we examined the effects of long-term administration of curcumin on vascular aging and chronic inflammation—the causes of arteriosclerotic disease. Eight-week-old C57BL/6J mice were fed with high fat diet (HFD) or 0.1% curcumin-mixed HFD (HFD + Cu) until 80 weeks old (n = 20 for each group). After the breeding, we examined the expression of antioxidant enzymes, heme oxygenase-1 (HO-1), oxidative stress, vascular aging, and inflammatory changes in the aorta. In the HFD group, oxidative stress increased with decreased sirt1 expression in the aorta followed by increased senescent cells and enhanced inflammation. Whereas in the HFD + Cu group, HO-1 was induced in the aorta with the suppression of oxidative stress. Additionally, it was shown that sirt1 expression in the aorta in the HFD + Cu group remained at a level comparable to that of the 8-week-old mice with suppression of increased senescent cells and enhanced inflammation. Consequently, disorders associated with HFD were resolved. These results suggest that curcumin might be a food with a prophylactic function against arteriosclerotic disease.

scholarly journals Oral Bisphenol A Worsens Liver Immune-Metabolic and Mitochondrial Dysfunction Induced by High-Fat Diet in Adult Mice: Cross-Talk between Oxidative Stress and Inflammasome Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1201
Author(s):  
Claudio Pirozzi ◽  
Adriano Lama ◽  
Chiara Annunziata ◽  
Gina Cavaliere ◽  
Clara Ruiz-Fernandez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Bisphenol A ◽  
Mitochondrial Dysfunction ◽  
Cross Talk ◽  
High Fat Diet ◽  
Additional Risk Factor ◽  
High Fat ◽  
Endocrine Disrupting Chemical ◽  
Glucose And Lipid Metabolism

Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression. This study evidences that BPA exposure represents an additional risk factor for the progression of fatty liver diseases strictly related to the cross-talk between oxidative stress and immune-metabolic impairment due to obesity.

scholarly journals Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 109 ◽  
Author(s):  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Mitochondrial Gene ◽  
Protective Effects ◽  
Drug Induced ◽  
Age Related ◽  
Cochlear Damage ◽  
Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

scholarly journals Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

2019 ◽  
Vol 241 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Hiranya Pintana ◽  
Piangkwan Sa-nguanmoo ◽  
Chiraphat Boonnag ◽  
Wasana Pratchayasakul ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Decline ◽  
Mitochondrial Dysfunction ◽  
Dendritic Spine ◽  
High Fat Diet ◽  
High Fat ◽  
Long Term Depression ◽  
Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

scholarly journals High-Fat Diet Increased Oxidative Stress and Mitochondrial Dysfunction Induced by Renal Ischemia-Reperfusion Injury in Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyanka N. Prem ◽  
Gino A. Kurian
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Ischemia Reperfusion ◽  
Protein Translation ◽  
Renal Ischemia ◽  
High Fat ◽  
Dietary Regimen ◽  
The Impact

Renal ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury influenced by the ischemic duration and the presence of comorbidities. Studies have reported that high-fat diet consumption can induce renal lipotoxicity and metabolic dyshomeostasis that can compromise the vital functions of kidney. This study aimed to evaluate the impact of a high-fat diet in the recovery of renal tissue from IR and explored the cellular pathology. In this study, 24 male Wistar rats were divided into two groups: normal diet (ND; n = 12) and high-fat diet (HD; n = 12), which were further subdivided into sham and IR groups at the end of the dietary regimen. The high-fat diet was introduced in 4-week-old rats and continued for 16 weeks. IR was induced by bilateral clamping of the renal peduncle for 45 min, followed by 24 h of reperfusion. Blood chemistry, estimated glomerular filtration rate (eGFR), mitochondrial function, and oxidative stress analysis were carried out to study the pathological changes. The rats fed with HD showed a decreased eGFR and elevated plasma creatinine, thereby compromised kidney function. Subcellular level changes in HD rats are deceased mitochondrial copy number, low PGC-1α gene expression, and declined electron transport chain (ETC) enzymes and adenosine triphosphate (ATP) level. Upon IR induction, HD rats exhibited severely impaired renal function (eGFR-0.09 ml/min) and elevated injury markers compared with ND rats. A histological analysis displayed increased tubular necrosis and cast formation in HD-IR in comparison to ND-IR. The oxidative stress and mitochondrial dysfunction were more prominent in HD-IR. In vitro protein translation assessment revealed impaired translational capacity in HD-IR mitochondria, which suggests mitochondrial changes with diet that may adversely affect the outcome of IR injury. High-fat diet consumption alters the normal renal function by modifying the cellular mitochondria. The renal changes compromise the ability of the kidney to recover from ischemia during reperfusion.

scholarly journals (-)-Epicatechin Mitigates High Fat Diet-induced Inflammation in the Hippocampus and Altered Recognition Memory in Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 411-411
Author(s):  
Jiye Kang ◽  
Ziwei Wang ◽  
Patricia Oteiza
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Object Recognition ◽  
Recognition Memory ◽  
High Fat Diet ◽  
High Fat ◽  
Short Term ◽  
Dietary Treatments ◽  
Metabolic Endotoxemia ◽  
And Oxidative Stress

Abstract Objectives This project investigated the capacity of dietary (-)-epicatechin (EC) to mitigate hippocampal inflammation and impaired memory in high fat diet (HFD)-fed mice. Methods Healthy 6 weeks old male C57BL/6J mice (10 mice/group) were fed for 13 weeks either: a control diet (10% total calories from fat), a high fat diet (60% total calories from lard fat), or the control and high fat diets supplemented with 20 mg EC/kg body weight. Between weeks 10 and 12 of the dietary intervention, object recognition memory was evaluated by the novel object recognition task and short-term spatial memory by the object location memory task, and the Morris Water Maze. After 13 weeks on the dietary treatments, mice were euthanized, and brain tissues and blood were collected. Hippocampus was isolated, flash-frozen in liquid nitrogen, and stored at −80°C. Metabolic endotoxemia was assessed by measuring plasma lipopolysaccharide (LPS) levels. Gene expressions related to inflammation (Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNF-α)), activation of microglia (ionized calcium-binding adapter molecule 1 (Iba-1)), and oxidative stress (NADPH oxidase 4 (NOX4)) were analyzed in the hippocampus with RT-qPCR. Results After 13 weeks on the dietary treatments, HFD-fed mice developed obesity, endotoxemia, and showed increased parameters of hippocampal inflammation, i.e., high mRNA levels of TLR4, Iba-1, and NOX4. While not affecting body weight gain, EC supplementation prevented all other HFD-induced changes. Impaired recognition memory was observed in HFD-fed mice, which was prevented by EC supplementation. Neither HFD consumption nor EC supplementation affected mouse spatial memory. Conclusions EC supplementation prevented short-term recognition memory in HFD-induced obese mice, which could be in part due to the capacity of EC to mitigate metabolic endotoxemia and associated hippocampal inflammation and oxidative stress. Funding Sources HA Jastro Shields Award.

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