Administration Of Docosahexaenoic Acid Research Articles

Omega-3 polyunsaturated fatty acids protect against cisplatin-induced nephrotoxicity by activating the Nrf2 signaling pathway

Nephrotoxicity is a prevalent side effect observed in patients undergoing chemotherapy. The pathogenesis of chemotherapy-induced nephrotoxicity involves various factors such as oxidative stress, DNA damage, inflammation, and apoptosis. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess anti-inflammatory and antioxidant properties. This study investigated the effects of EPA and DHA, either alone or in combination, on cisplatin-induced nephrotoxicity in mice, as well as their underlying mechanisms of action. The combined administration of EPA and DHA demonstrated superior efficacy in mitigating cisplatin-induced nephrotoxicity compared to administration alone, including the reduction of oxidative damage, inflammation, and apoptosis. Moreover, the combination of EPA and DHA suppressed inflammation and prevented the development of chronic kidney fibrosis during prolonged observations following repeated cisplatin administration. Mechanistically, ω-3 PUFAs enhance the expression of antioxidant genes by activating the p62-Keap1-Nrf2 signaling pathway. Furthermore, Nrf2 activation can inhibit the cisplatin-induced p53 apoptosis signal by upregulating the expression of MDM2 in renal tubular epithelial cells. Consequently, ω-3 PUFAs exert a protective effect against cisplatin-induced renal injury through activating the Nrf2 signaling pathway, suggesting that ω-3 PUFAs intake holds promise as a therapeutic strategy for combating cisplatin-induced nephrotoxicity.

The effect of docosahexaenoic acid (DHA) supplementation on total antioxidant capacity (TAC), superoxide dismutase (SOD), and interleukin-6 levels in underweight pregnant women

HIGHLIGHTS Underweight pregnant women, face an imbalance in energy and protein intake. TAC, SOD, and IL6 with administration of DHA to pregnant women with chronic energy deficiency in the third trimester provide benefits. ABSTRACT Objective: Underweight pregnant women face oxidative stress and inflammation, increasing their risk of intrauterine growth restriction (IUGR) and preterm birth. This study investigates the effects of DHA supplementation on Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), and Interleukin-6 (IL-6) in underweight pregnant women, along with the correlation between DHA and these markers. Materials and Methods: This experimental pre-test/post-test study focused on underweight pregnant women in the Made District, Surabaya, Indonesia. Eligible participants were in their second or third trimester, had a BMI below 18.5, and were taking DHA regularly. Exclusion criteria included early pregnancy (gestational age < 14 weeks), BMI above 18.5, irregular DHA intake, and withdrawal from the study. The study ran from July to December 2023, using non-probability sampling to select participants. Blood samples were collected before and after two months of DHA supplementation. Results: Following the intervention, TAC levels demonstrated a noteworthy increase (p < 0.05). SOD levels also exhibited a significant difference (p <0.05), and IL-6 levels showed a significant change (p < 0.05). A strong and positive correlation (r = 0.718) was observed between the increased TAC and SOD levels. DHA influenced both TAC and IL-6, with a significant relationship between TAC and IL-6 (p < 0.01). Furthermore, elevated SOD levels were associated with a decrease in IL-6 levels (p < 0.01). The correlation coefficient value of 0.718 between changes in SOD and TAC indicated a robust positive correlation. Conclusion: The findings suggest that DHA supplementation in underweight pregnant women positively affects oxidative stress and inflammation markers, improving TAC, SOD, and IL-6 levels.

Docosahexaenoic acid protects against ischemic stroke in diabetic mice by inhibiting inflammatory responses and apoptosis

This study was to explore whether docosahexaenoic acid (DHA) protects against ischemic stroke in diabetic mice and its mechanisms. DHA was administered to mice and its effects on stroke outcomes in type 1 diabetes mellitus were assessed 24 h and 3 days post-reperfusion using RNA sequencing, flow cytometry, multiplex immunoassays, and western-blotting analysis. In diabetic mice, DHA administration post-ischemic stroke significantly reduced cerebral infarct size, brain edema, and neurological impairments. Flow cytometric analysis demonstrated a notable decrease in the percentage of neutrophils in the ischemic brain, suggesting a mitigated inflammatory response. Western blotting assay revealed that pro-apoptotic protein Bax was reduced whereas anti-apoptotic protein Bcl-2 was increased, indicating the attenuation of apoptosis. Additionally, RNA sequencing of brain tissue highlighted significant transcriptomic changes, with downregulation of genes for several inflammatory pathways such as NF-kappa B signaling and upregulation of genes for neuroprotective pathways such as neuroactive ligand-receptor interaction. Similar transcriptomic changes in peripheral blood mononuclear cells indicated that DHA treatment resulted the systemic anti-inflammatory and neuroprotective response. DHA treatment mitigated cerebral ischemic injuries by dampening inflammatory responses and apoptosis in diabetic mice after ischemic stroke, highlighting its therapeutic potential for clinical management of stroke in diabetic patients.

DHA and EPA alleviate depressive-like behaviors in chronic sleep-deprived mice: Involvement of iron metabolism, oligodendrocyte-lipids peroxidation and the LCN2-NLRP3 signaling axis

Mounting evidence suggests that eicosapentaenoic acid (EPA) is superior to docosahexaenoic acid (DHA) in the treatment of depression, but the underlying mechanisms remain elusive. In the present study, the effect of DHA and EPA on depressive-like behaviors was investigated in chronic sleep-deprived (CSD) mice. Following the administration of EPA or DHA, investigations were conducted on depression-like behavior, myelin damage, iron dyshomeostasis, oligodendrocyte-lipids peroxidation, and neuroinflammation. As anticipated, EPA was more effective than DHA in ameliorating CSD-induced depression by increasing center preference and immobility time and concurrently shortening immobility latency. Both DHA and EPA mitigated myelin damage with EPA demonstrating superior benefits characterized by higher levels of Olig2, MBP, and FTH, as well as decreased oligodendrocyte-lipid peroxidation. The inhibition of activated astrocytes and the associated LCN2-NLRP3 signaling pathway was observed following both EPA and DHA supplementation. However, the inhibitory effect was more pronounced with EPA. Additionally, EPA outperformed DHA in mitigating microglial activation and M1/M2 polarization imbalance. Overall, this present study provides valuable insights into the anti-depressive effects of DHA and EPA, highlighting their role in inhibiting oligodendrocyte-lipids peroxidation and the LCN2-NLRP3 axis and corroborating the superiority of EPA in mediating antidepressant effects.

Docosahexaenoic Acid and Sleep Quality in Very and Extreme Preterm Infants.

The results regarding the association of plasma docosahexaenoic acid (DHA) levels with sleep duration conflict. This study aimed to investigate the effect of oral administration of DHA on the sleep quality of Brazilian extreme preterm infants. This cohort study is part of the Joinville Docosahexaenoic Acid Study (JoiDHA) conducted with 59 infants in Joinville, Brazil. Sleep quality was assessed using the Brief Infant Sleep Questionnaire, which consists of 12 questions about the quality of sleep the week prior to its application and was answered by the parents/guardians. Of the 59 children who participated in the study, 37 (62.7%) were supplemented with DHA and 22 (37.3%) did not receive DHA. The prevalence of poor sleep quality was higher among children with the weight status at birth <50th percentile (68.2%; p = 0.045) when compared to children ≥50th percentile. However, Poisson regression analysis showed that neither weight status at birth nor DHA use was associated with sleep quality, even after adjusting for the same variables. In summary, sleep quality 12-24 months after birth was not associated with DHA supplementation in very and extreme preterm infants. Additional studies that address the increase in DHA intake would be important for the understanding of the effect of this fatty acid on sleep quality.

Docosahexaenoic acid (DHA) alleviates inflammation and damage induced by experimental colitis.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8-10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects.

Role of antioxidative activity in the docosahexaenoic acid's enteroprotective effect in the indomethacin-induced small intestinal injury model.

Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment. Pathogenesis of NSAID-induced small intestinal injury is multifactorial, and reactive oxidative species have been related to indomethacin's small intestinal damage. The present work aimed to evaluate antioxidative activity in the protective action of DHA in the indomethacin-induced small intestinal damage. Female Wistar rats were gavage with DHA (3 mg/kg) or omeprazole (3 mg/kg) for 10 days. Each rat received indomethacin (3 mg/kg, orally) daily to induce small intestinal damage. The total area of intestinal ulcers and histopathological analysis were performed. In DHA-treated rats, myeloperoxidase and superoxide dismutase activity, glutathione, malondialdehyde, leukotriene, and lipopolysaccharide (LPS) levels were measured. Furthermore, the relative abundance of selective bacteria was assessed. DHA administration (3 mg/kg, p.o.) caused a significant decrease in indomethacin-induced small intestinal injury in Wistar rats after 10 days of treatment. DHA's enteroprotection resulted from the prevention of an increase in myeloperoxidase activity, and lipoperoxidation, as well as an improvement in the antioxidant defenses, such as glutathione levels and superoxide dismutase activity in the small intestine. Furthermore, we showed that DHA's enteroprotective effect decreased significantly LPS levels in indomethacin-induced injury in small intestine. Our data suggest that DHA's enteroprotective might be attributed to the prevention of oxidative stress.

Infection, Inflammation, and Immunity in Sepsis.

Sepsis is triggered by microbial infection, injury, or even major surgery. Both innate and adaptive immune systems are involved in its pathogenesis. Cytoplasmic presence of DNA or RNA of the invading organisms or damaged nuclear material (in the form of micronucleus in the cytoplasm) in the host cell need to be eliminated by various nucleases; failure to do so leads to the triggering of inflammation by the cellular cGAS-STING system, which induces the release of IL-6, TNF-α, and IFNs. These cytokines activate phospholipase A2 (PLA2), leading to the release of polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which form precursors to various pro- and anti-inflammatory eicosanoids. On the other hand, corticosteroids inhibit PLA2 activity and, thus, suppress the release of GLA, AA, EPA, and DHA. PUFAs and their metabolites have a negative regulatory action on the cGAS-STING pathway and, thus, suppress the inflammatory process and initiate inflammation resolution. Pro-inflammatory cytokines and corticosteroids (corticosteroids > IL-6, TNF-α) suppress desaturases, which results in decreased formation of GLA, AA, and other PUFAs from the dietary essential fatty acids (EFAs). A deficiency of GLA, AA, EPA, and DHA results in decreased production of anti-inflammatory eicosanoids and failure to suppress the cGAS-STING system. This results in the continuation of the inflammatory process. Thus, altered concentrations of PUFAs and their metabolites, and failure to suppress the cGAS-STING system at an appropriate time, leads to the onset of sepsis. Similar abnormalities are also seen in radiation-induced inflammation. These results imply that timely administration of GLA, AA, EPA, and DHA, in combination with corticosteroids and anti-IL-6 and anti-TNF-α antibodies, may be of benefit in mitigating radiation-induced damage and sepsis.

Changes of Erythrocyte Fatty Acids after Supplementation with Highly Concentrated Docosahexaenoic Acid (DHA) in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

We characterized the fatty acid profiles in the erythrocyte membrane of pediatric patients with cystic fibrosis (CF) receiving highly concentrated docosahexaenoic acid (DHA) supplementation (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day (n = 11) or matching placebo (n = 11) for 12 months. The mean age was 11.7 years. The DHA group showed a statistically significant improvement in n-3 polyunsaturated fatty acids (PUFAs), which was observed as early as 6 months and further increased at 12 months. Among the n-3 PUFAs, there was a significant increase in DHA and eicosapentaenoic acid (EPA). Additionally, a statistically significant decrease in n-6 PUFAs was found, primarily due to a decrease in arachidonic acid (AA) levels and elongase 5 activity. However, we did not observe any changes in linoleic acid levels. The long-term administration of DHA over one year was safe and well tolerated. In summary, the administration of a high-rich DHA supplement at a dose of 50 mg/kg/day for one year can correct erythrocyte AA/DHA imbalance and reduce fatty acid inflammatory markers. However, it is important to note that essential fatty acid alterations cannot be fully normalized with this treatment. These data provide timely information of essential fatty acid profile for future comparative research.

Docosahexaenoic acid administration improves diabetes-induced cardiac fibrosis through enhancing fatty acid oxidation in cardiac fibroblast

Diabetes mellitus can lead to various complications, including organ fibrosis. Metabolic remodeling often occurs during the development of organ fibrosis. Docosahexaenoic acid (DHA), an essential ω-3 polyunsaturated fatty acid, shows great benefits in improving cardiovascular disease and organ fibrosis, including regulating cellular metabolism. In this study, we investigated whether DHA can inhibit diabetes-induced cardiac fibrosis by regulating the metabolism of cardiac fibroblasts. Type I diabetic mice were induced by streptozotocin and after supplementation with DHA for 16 weeks, clinical indicators of serum and heart were evaluated. DHA administration significantly improved serum lipid levels, cardiac function and cardiac interstitial fibrosis, but not blood glucose levels. Subsequently, immunofluorescences, western blot and label-free quantitative proteomics methods were used to study the mechanism. The results showed that the anti-fibrotic function of DHA was achieved through regulating extracellular matrix homeostasis including ECM synthesis and degradation. Our research demonstrated DHA regulated the energy metabolism of cardiac fibroblasts, especially fatty acid oxidation, and then affected the balance of ECM synthesis and degradation. It suggested that DHA supplementation could be considered an effective adjuvant therapy for cardiac fibrosis caused by hyperglycemia.

DHA and EPA Prevent Seizure and Depression-Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode-of-Actions in a Pentylenetetrazole-Induced Kindling Model in Mice.

It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anticonvulsant effects, yet the respective mechanism of EPA and DHA on epilepsy is still unclarified. This study aims to investigate the effect of EPA and DHA on pentylenetetrazol (PTZ) induced seizures and depression. The administration of EPA and DHA at a dose of 1% w/w significantly inhibits PTZ-induced seizures and depressive-like behavior, whereas EPA outcompetes DHA. Further mechanistic studies reveal that the higher effect of EPA can be partly attributed to the promotion of M2 polarization, inhibition of M1 polarization of microglia, and lower iron content in the brain, resulting from the stronger activation of nuclear factor E2-related factor 2 (Nrf2). This study finds that DHA and EPA comparably inhibit NLRP3 inflammasome activation but with different mode-of-actions: EPA prefers to inhibit the binding of NLRP3 and ASC, while DHA decreases the protein levels of ASC and Caspase-1. These results indicate that DHA and EPA can efficaciously alleviate PTZ-induced seizure and depressive-like behavior but with different efficiency and molecular mechanisms.

The protective effect of docosahexaenoic acid on the stomach in Parkinson’s disease induced by MPTP in male C57BL/6 mice

The purpose of this study was to detect gastric changes in Parkinson’s disease induced by 1-methyl-4-phenyl-1.2.3.6.-tetrahydropyridine (MPTP), and to investigate the protective effect of docosahexaenoic acid (DHA) against these changes in mice. The mice were divided into 4 groups (n=10 in per group) as control, DHA, Parkinson and DHA+Parkinson groups. DHA was administered by gavage for 30 days. On the 23rd day of gavage treatment, the animals of the Parkinson and DHA+Parkinson groups were intraperitoneally injected with MPTP. Seven days after the injection of MPTP, their locomotor activity, bradykinesia and rotarod performance were measured. Tyrosine hydroxylase expression in substantia nigra and the apoptotic index, the concentrations of tumor necrosis factor-α and histamine, and the number of mast cells in the stomach were evaluated. Administration of DHA significantly prevented the reduction in motor functions (P&lt;0.001) and nigral TH neurons (P&lt;0.05), and apoptosis (P&lt;0.05), and an increase in TNF-α concentration (P&lt;0.01) in the stomach. An increase in the number of mast cells in the stomach wall was observed in PD (P&lt;0.001). DHA prevented the increase in the number of mast cells (P&lt;0.05) and the histamine level (P&lt;0.01) due to PD. As a result, MPTP administration in mice caused changes in the stomach as well as impairment in motor functions, and DHA was observed to reduce these changes.

Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease.

Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 n-3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain. Several studies have reported reduced brain DHA concentrations in Alzheimer’s disease (AD) patients’ brains. Although a number of epidemiological studies suggest that dietary DHA consumption may protect the elderly from developing cognitive impairment or dementia including AD, several review articles report an inconclusive association between omega-3 PUFAs intake and cognitive decline. The source of these inconsistencies might be because DHA is highly oxidizable and its accessibility to the brain is limited by the blood–brain barrier. Thus, there is a pressing need for new strategies to improve DHA brain supply. In the present study, we show for the first time that the intranasal administration of nanovectorized DHA reduces Tau phosphorylation and restores cognitive functions in two complementary murine models of AD. These results pave the way for the development of a new approach to target the brain with DHA for the prevention or treatment of this devastating disease.

Docosahexaenoic Acid-Enhanced Autophagic Flux Improves Cardiac Dysfunction after Myocardial Infarction by Targeting the AMPK/mTOR Signaling Pathway.

Background and Purpose. Docosahexaenoic acid (DHA) is a type of polyunsaturated fatty acid enriched in cod liver oil and seaweed. It is necessary for the human body and has important functions, such as antioxidation and antiatherosclerosis activities. Long-term oral administration of DHA or the use of DHA at the initial stage of ischemia can increase the level of autophagy and exert a protective effect on neurological functions related to cerebral infarction. However, the effect of DHA on myocardial injury and cardiac insufficiency after myocardial infarction (MI) is unknown. This study was aimed at exploring whether DHA plays a protective role in AMI and its specific molecular mechanism. Experimental Method. In vitro cardiomyocyte hypoxia and in vivo MI injury models were used to determine the role of DHA in MI. Hypoxic injury induced damage in cultured neonatal mouse cardiomyocytes (NMCs). The C57BL/6J mouse MI model was established by permanent ligation of the left anterior descending branch. Main Results. DHA improved the cardiomyocyte viability of NMCs induced by hypoxia injury and reduced cell necrosis. DHA reduced infarct size, improved heart function, and reduced the degree of myocardial fibrosis in mice after MI. In addition, DHA enhanced autophagy flux and reduced apoptosis in vitro and in vivo. In addition, we found that chloroquine, an autophagy inhibitor, blocked the protective effect of DHA on cardiomyocyte apoptosis and cardiac dysfunction, indicating that DHA exerts cardioprotective effects in part by promoting autophagy flux. We also observed that DHA enhanced autophagy flux by activating the AMPK/mTOR signaling pathway. Conclusions and Significance. In conclusion, our findings indicate for the first time that DHA improves MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

Up-regulation of IRF3 is required for docosahexaenoic acid suppressing ferroptosis of cardiac microvascular endothelial cells in cardiac hypertrophy rat

The molecular characteristics of ferroptosis in cardiac hypertrophy have been rarely studied. Especially, there have been no studies to investigate the regulatory mechanisms of docosahexaenoic acid (DHA) on ferroptosis in cardiac hypertrophy. This study was designed to determine the role of ferroptosis in microvascular injury, and investigate the contribution of DHA in suppressing ferroptosis and preventing pressure overload-mediated endothelial damage. Our results indicated that the expression of interferon regulating factor 3 (IRF3) was primarily inhibited by pressure overload and consequently caused endothelial ferroptosis. Nevertheless, administration of DHA increased IRF3 expression and provided a pro-survival advantage for the endothelial system in the context of pressure overload. Experimental studies clearly showed that inhibition of IRF3 down-regulated SLC7A11 expression, and the latter leaded to the increase in the activities of arachidonate 12-lipoxygenase, which obligated cardiac microvascular endothelial cells to undergo ferroptosis via augmenting lipid peroxides. Interestingly, DHA supplementation suppressed endothelial ferroptosis via up-regulation of IRF3. Taken together, our studies identified the IRF3-SLC7A11-arachidonate 12-lipoxygenase axis as a new pathway responsible for pressure overload-mediated microvascular damage via initiating endothelial ferroptosis. In contrast, DHA treatment up-regulated the expression of IRF3 and thus reduced cellular ferroptosis, conferring a protective advantage to the endothelial system in pressure overload. These findings revealed that targeting IRF3 might be a useful therapeutic strategy for cardioprotection in cardiac hypertrophy and heart failure.

Docosahexaenoic Acid Attenuates the Progression of Nonalcoholic Steatohepatitis by Suppressing the Adipocyte Inflammation via the G Protein-Coupled Receptor 120/Free Fatty Acid Receptor 4 Pathway

Introduction: Our previous study demonstrated that docosahexaenoic acid (DHA), an endogenous G protein-coupled receptor 120 (GPR120)/free fatty acid receptor (FFAR) 4 agonist, attenuated the liver inflammation in nonalcoholic steatohepatitis (NASH), while exacerbated liver inflammation was observed in the GPR120/FFAR4 knockout (GPR120/FFAR4KO) mice. Recently, abdominal adiposity has been reported to correlate with the severity of inflammation and fibrosis in patients with NASH. In this study, we investigated whether the activation of GPR120/FFAR4 suppressed the inflammation of the adipose tissue and whether these suppressive effects attenuated the development of NASH. Methods: A choline-deficient and 0.1% methionine-containing high-fat (CDAHF) diet was used to create a mouse model of NASH. DHA was orally administered to the mice for 1 week. Epididymal fat pads which collected from the control-fed wild-type (WT) or GPR120/FFAR4KO mice were used as ex vivo white adipose tissue (WAT) culture systems. Results: The mice fed a CDAHF diet for 2 weeks showed NASH-like liver diseases. In the WAT of mice fed with the CDAHF diet, inflammation and fibrosis were significantly increased, and the administration of DHA suppressed these phenomena. In an ex vivo adipocyte culture study, DHA dose-dependently suppressed the lipopolysaccharide-induced inflammation in the adipocyte tissue of WT mice, which was reversed by pretreatment with AH7614, a GPR120/FFAR4 antagonist, but not GPR40 or peroxisome proliferator-activated receptor γ antagonist. Conclusions: These findings suggest that the activation of GPR120/FFAR4 may suppress the inflammation of adipocytes, which could be a key pathway to prevent the development of NASH.

Iduna contributes to the therapeutic effect of DHA in acell and mouse model of traumatic brain injury via Wnt/MDM2 pathway.

Traumatic brain injury (TBI) is a severe condition that leads to brain damage and affects brain function. Importantly, TBI incurs public health costs due to its high mortality, and effective treatment for TBI is still lacking. Docosahexaenoic acid (DHA) has a neuroprotective effect that can reduce oxidative, apoptosis, and inflammatory processes. Administration of DHA after TBI attenuates oxidative stress and protein accumulation and is regarded as a potential therapeutic. Iduna is a regulator of parthanatos, and upregulation of Iduna reduces cellular damage and mitochondrial dysfunction. Thus, we speculated that overexpression of Iduna might promote DHA therapy in the treatment of TBI. Here, we found that after combination overexpression of Iduna and DHA in a mouse model of TBI, the expression of inflammatory factors was reduced, while the secretion of neuroprotective factors was increased. In addition, we found that these effects might be mediated by the Wnt/MDM2 pathway, and Iduna might be a therapeutic target for TBI.

Docosahexaenoic acid administration to a dog with idiopathic epilepsy: a case study

Docosahexaenoic acid administration to a dog with idiopathic epilepsy: a case study

SUPLEMENTASI DOCOSAHEXAENOIC ACID (DHA) SEBAGAI USAHA PREVENTIF IBU HAMIL DENGAN RISIKO PREEKLAMPSIA

Hypertension in pregnancy is one of the main cause of maternal death in the world. Hypertensive disorders in pregnancy, including preeclampsia, have a broad spectrum of conditions associated with maternal and fetal morbidity and mortality. Preeclampsia is a syndrome characterized by new onset of hypertension at ≥20 weeks of gestation, in pregnant women who were previously normotensive and accompanied by proteinuria. This paper aims to determine the effectiveness of docosahexaenoic acid (DHA) in pregnant women to prevent the risk of preeclampsia. This research method is to review the articles published in the last 10 years with the keywords preeclampsia, therapy, preventive, and docosahexaenoic acid (DHA). The data show that administration of docosahexaenoic acid (DHA) can reduce the risk of preeclampsia with minimal side effects for both maternal and the fetus. DHA on the other hand is still insignificant in preventing preeclampsia in high-risk pregnant women and prescribing the high dose of DHA is not recommended for pregnant women. DHA will be more effective in preventing preeclampsia if given in early pregnancy, especially in the first trimester of pregnancy

Maternal intake of docosahexaenoic acid decreased febrile seizure sensitivity by increasing estrogen synthesis in offspring

Febrile seizures, which are convulsion in children, are caused by an abrupt increase in body temperature. They are sometimes recurrent, and the more seizures are triggered, the higher the risk of epilepsy and psychiatric disorders increase after growing up. Prevention of febrile seizure is considered to be one of the effective countermeasures in protecting the future health of children; however, pharmacological prevention in the developmental stage is not realistic from the health aspects of the offspring. Docosahexaenoic acid (DHA) is an important nutrient especially during pregnancy and childhood and is reported to suppress several types of epilepsy. The purpose of this study was to examine the effect of DHA intake during pregnancy and infancy on febrile seizures in mice. We used a heat chamber for febrile seizure induction in offspring at the age of from 10 to 11 days old. Intake of DHA during pregnancy and infancy significantly increased the amount of DHA in the brain of offspring. Although DHA had no effect on seizure severity, DHA significantly prolonged the seizure latency and increased body temperature at which the first seizure occurred, indicating that maternal DHA intake decreases febrile seizure sensitivity. Brain estrogen levels significantly increased by DHA intake and administration of an inhibitor for cytochrome P450 aromatase, which is a rate-limiting enzyme for estrogen synthesis, clearly decreased seizure latency and body temperature at which the first seizure occurred. Taken together, DHA could reduce susceptibility to febrile seizures owing to increases in brain estrogen contents. DHA intake during pregnancy and infancy is of significance in protecting infant from seizures as well as conserving health after growth.