Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish

Cansız, Derya; Ünal, İsmail; Üstündağ, Ünsal Veli; Alturfan, A. Ata; Altinöz, Meriç A.; Elmacı, İlhan; Emekli-Alturfan, Ebru

doi:10.1007/s11033-021-06532-5

Cited by 39 publications

(23 citation statements)

References 59 publications

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“…Most of these studies, however, reflected the total distance swam, velocity, and freezing episodes reunited under the locomotion impairment umbrella rather than the social and aggressive components. Exposure to 2 µg/L ROT cause non-motor to mild symptoms [ 12 , 13 ], whereas 5 μg/L [ 14 , 15 , 16 , 17 ] up to 2 mg/L [ 27 , 28 ] might lead to excessive mortality, as in our case (unpublished data), or sufficient to induce a targeted phenotype.…”

Section: Discussionmentioning

confidence: 54%

“…Our team [ 12 ] and Wang et al [ 13 ] revealed that 2 µg/L over 21–28 days causes mild symptomatology. Thus, we performed some preliminary experiments prior to the actual protocol in which up to 5 zebrafish subjects per tank were exposed to three different doses (from 2 µg/L, 2.5 µg/L, and 5 µg/L) for 24 up to 72 h and concluded that 2.5 µg/L might be optimum, since 5 µg/L led to high mortality (data not shown) despite the existing evidence in the literature indicating a significant locomotor impairment (between 28 and 30 days of exposure) [ 14 , 15 , 16 , 17 ]. An analogous approach was applied for VPA, where we tested four doses (0.5 mg/mL, 2 mg/mL, 5 mg/mL, and 10 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

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Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson’s Disease Chronically Exposed to Rotenone

et al. 2022

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Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson’s disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood–brain barrier (BBB) and accumulates in mitochondria. Unfortunately, most of the existing data focus on locomotion. This is why the present study aimed to bring novel evidence on how ROT alone or in combination with different potential ant(agonists) might influence the social and aggressive behavior using the counterclockwise rotation as a neurological pointer. Material and Methods: Thus, we exposed zebrafish to ROT—2.5 µg/L, valproic acid (VPA)—0.5 mg/mL, anti-parkinsonian drugs (LEV/CARB)—250 mg + 25 mg, and probiotics (PROBIO)—3 g for 32 days by assessing the anti-social profile and mirror tests and counterclockwise rotation every 4 days to avoid chronic stress. Results: We observed an abnormal pattern in the counterclockwise rotation only in the (a) CONTROL, (c) LEV/CARB, and (d) PROBIO groups, from both the top and side views, this indicating a reaction to medication and supplements administered or a normal intrinsic feature due to high levels of stress/anxiety (p < 0.05). Four out of eight studied groups—(b) VPA, (c) LEV/CARB, (e) ROT, and (f) ROT + VPA—displayed an impaired, often antithetical behavior demonstrated by long periods of time on distinct days spent on the right and the central arm (p < 0.05, 0.005, and 0.001). Interestingly, groups (d) PROBIO, (g) ROT + LEV/CARB, and (h) ROT + PROBIO registered fluctuations but not significant ones in contrast with the above groups (p > 0.05). Except for groups (a) CONTROL and (d) PROBIO, where a normalized trend in terms of behavior was noted, the rest of the experimental groups exhibited exacerbated levels of aggression (p < 0.05, 0.005, and 0.001) not only near the mirror but as an overall reaction (p < 0.05, 0.005, and 0.001). Conclusions: The (d) PROBIO group showed a significant improvement compared with (b) VPA, (c) LEV/CARB, and ROT-treated zebrafish (e—h). Independently of the aggressive-like reactions and fluctuations among the testing day(s) and groups, ROT disrupted the social behavior, while VPA promoted a specific typology in contrast with LEV/CARB.

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Section: Discussionmentioning

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson’s Disease Chronically Exposed to Rotenone

et al. 2022

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“…We have recently shown the amelioration of rotenone-induced oxidative stress and inflammation in both brain and intestines and improvement of locomotor activity in adult zebrafish by caprylic acid treatment. Caprylic acid decreased lipid peroxidation, nitric oxide levels, and increased superoxide dismutase activities and normalized the expressions of tnf⍺, il1, il6, il21, ifnɣ, and bdnf in brain and intestines (Cansız et al, 2021). We designed our current study to investigate the phosphoproteomic mechanisms of the effects of octanoic acid in rotenone-induced neurotoxicity and here we present the results of global, quantitative phosphoproteomic analysis of the effects of octanoic acid in rotenone exposed zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Quantitative phosphoproteomics to resolve the cellular responses to octanoic acid in rotenone exposed zebrafish

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Cansız

et al. 2021

J Food Biochem

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Ketosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson's disease (PD). Medium-chain-triglycerides (MCT) have specific metabolic properties and they are described as ketogenic even without restriction of carbohydrate. Octanoic acid (C8) is the main MCT showing this effect.Rotenone is a neurotoxin that is used to induce experimental PD model. Rotenone inhibits mitochondrial respiratory complex 1 (MRC1) and causes reactive oxygen species formation. Mass spectrometry (MS)-based phosphoproteomic methods enable discovering specific signaling events in special molecular pathways through identification and quantification of phosphoproteins. Signaling networks involved in rotenonemediated biological processes and beneficial effects of MCTs on neurodegenerative diseases are not well understood. We aimed to gain comprehensive molecular perspective on the global phosphoproteome differences in rotenone-exposed zebrafish treated with octanoic acid. Raw files obtained from MS analysis were processed and searched against the Danio rerio protein database using SEQUEST-HT algorithm to identify and quantify phosphopeptides with 2,569 unique phosphoproteins and 4,161 unique phosphopeptides corresponding to 2005 proteins. Microtubuleassociated protein (MAP) family members were significantly lower in rotenone group.Phosphoproteins involved in ion binding (calcium, magnesium, zinc ion), oxygen binding, microtubule binding, ATP-and GTP-binding were among differentially expressed 347 proteins in rotenone group and they were reversed after octanoic acid treatments. Phosphoproteins and phosphorylation sites were identified for future exploration of signaling pathways involved in rotenone toxicity. We believe our findings might help in the formulation of effective therapeutic strategies for the treatment of PD using ketogenic formulations involving MCTs. Practical applicationsKetosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson's disease (PD). Medium-chain-triglycerides (MCT) (C6-C12) have specific metabolic properties making them described as ketogenic even without restriction of carbohydrate. Octanoic acid (caprylic acid, C8) is the main MCT showing this effect. Our findings might help in the formulation of effective

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“…Secondly, octanoate could reduce the oxidative stress and inflammatory response. In zebrafish, octanoate ameliorated rotenone-induced oxidative stress and inflammatory response in the gut-brain axis ( 8 ). In mice, octanoate also inactivated Toll-like receptors (TLRs) to reduce the inflammatory response ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea)

et al. 2022

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Octanoate is a type of classical medium-chain fatty acids, which is widely used to treat neurological and metabolic syndrome. However, the specific role of octanoate in repairing intestinal health impairment is currently unknown. Therefore, we investigated whether dietary octanoate repaired the intestinal damage induced by surplus soybean oil in Larimichthys crocea. In this study, dietary octanoate alleviated abnormal morphology of the intestine and enhanced expression of ZO-1 and ZO-2 to improve intestinal physical barrier. Further, dietary octanoate increased antioxidant enzymic activities and decreased the level of ROS to alleviate the intestinal oxidative stress. Dietary octanoate also attenuated the expression of proinflammatory cytokines and the polarity of macrophage to reduce the intestinal inflammatory response. Moreover, the result of intestinal microbial 16S rRNA sequence showed that dietary octanoate repaired the intestinal mucosal microbial dysbiosis, and increased the relative abundance of Lactobacillus. Dietary octanoate supplementation also increased the level of acetic acid in intestinal content and serum through increasing the abundance of acetate-producing strains. Overall, in Larimichthys crocea, dietary octanoate might alleviated oxidative stress, inflammatory response and microbial dysbiosis to repair the intestinal damage induced by surplus soybean oil. This work provides vital insights into the underlying mechanisms and treatment strategies for intestinal damage in vertebrates.

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Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish

Cited by 39 publications

References 59 publications

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson’s Disease Chronically Exposed to Rotenone

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson’s Disease Chronically Exposed to Rotenone

Quantitative phosphoproteomics to resolve the cellular responses to octanoic acid in rotenone exposed zebrafish

Octanoate Alleviates Dietary Soybean Oil-Induced Intestinal Physical Barrier Damage, Oxidative Stress, Inflammatory Response and Microbial Dysbiosis in Large Yellow Croaker (Larimichthys Crocea)

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