Ethanol Toxicity Research Articles

Transgenic expression of human cytochrome P450 2E1 in C. elegans and rat PC-12 cells sensitizes to ethanol-induced locomotor and mitochondrial effects

Chronic alcohol (ethanol) use is increasing in the United States and has been linked to numerous health issues in multiple organ systems including neurological dysfunction and diseases. Ethanol toxicity is mainly driven by the metabolite acetaldehyde, which is generated through three pathways: alcohol dehydrogenase (ADH2), catalase (CAT), and cytochrome P450 2E1 (CYP2E1). ADH2, while the main ethanol clearance pathway in the liver, is not expressed in the mammalian brain, resulting in CAT and CYP2E1 driving local metabolism of ethanol in the central nervous system. CYP2E1 is known to generate reactive metabolites and reactive oxygen species and localizes to the mitochondria (mtCYP2E1) and endoplasmic reticulum (erCYP2E1). We sought to understand the consequences of mtCYP2E1 and erCYP2E1 in the nervous system during acute ethanol exposure. To answer this question, we generated transgenic Caenorhabditis elegans roundworms expressing human CYP2E1 in the mitochondria, endoplasmic reticulum, or both and exposed them to ethanol. We found that at lower concentrations, wild-type and mtCYP2E1-expressing worms had a small but significant inhibition of locomotion, whereas the erCYP2E1-expressing worms showed protection from this inhibition. At higher doses, all strains had reduced locomotion, but the erCYP2E1-expressing worms recovered faster than wild-type controls. CYP2E1 expression, regardless of organellar targeting, reduced mitochondrial respiration in response to ethanol. Similarly, transgenic expression of CYP2E1 in either organelle in PC-12 rat neuronal cell lines sensitized them to ethanol-induced cell death. Together, these findings suggest that subcellular localization of CYP2E1 impacts behavioral effects of ethanol and should be further studied in the mammalian central nervous system.

Hepatoprotective potentials of Usnea longissima Ach. and Xanthoparmelia somloensis (Gyelnik) Hale extracts in ethanol-induced liver injury

In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.

Lamivudine protects mice from gastric ulcer by activating PGK1 to suppress ferroptosis

Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1.

Genome analysis of Hanseniaspora vineae CC-P5 and CC-ZZ6 isolate from grapes reveals the biotech potential for winemaking

The genus Hanseniaspora is a non-Saccharomyces yeast frequently isolated from wine-associated environments and has been recognized to play a key role in winemaking. However, most of the research on Hanseniaspora focused on its role in fermentation or its coordination with Saccharomyces cerevisiae, but the genome data of Hanseniaspora is very scarce, which is not conducive to better utilization and development of this yeast. Therefore, in this study, the genome data of two Hanseniaspora vineae strains CC-P5 and CC-ZZ6 with flocculation and antimicrobial abilities were sequenced and bioinformatics analyses were performed. The results showed that the genomes of the two strains have a high degree of homology with an average nucleotide identity of 97.7 %. Both H. vineae CC-P5 and CC-ZZ6 have corresponding genes for adaptability to osmotic stress, sulfur dioxide stress, ethanol toxicity and other stresses, as well as various genes involved in the biosynthesis of ethyl esters, volatile organic acids, aromatic amino acid, benzyl alcohol/benzaldehyde and terpenoid, which are useful for modulating wine flavor and aroma. These results shed light on why H. vineae has the biotechnology to make wine. In addition, the number of publicly available H. vineae genome databases have increased. This has laid the foundation for further research on Hanseniaspora.

The Role of Cytokines in the Pathogenesis and Treatment of Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The pathogenesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counter the progression of chronic alcohol-related liver disease and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of inhibiting pro-inflammatory cytokines and stimulating anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the main cytokines involved in the pathogenesis and treatment of ALD.

The ameliorative effect of turmeric (Curcuma longa Linn) extract and its major constituent, curcumin, and its analogs on ethanol toxicity.

Ethanol toxicity is a major public health problem that can cause damage to various organs in the body by several mechanisms inducing oxidative stress, inflammation, and apoptosis. Recently, there has been a growing interest in the potential of herbal medicines as therapeutic agents for the prevention and treatment of various disorders. Turmeric (Curcuma longa) extracts and its main components including curcumin have antioxidant, anti-inflammatory, and anti-apoptotic properties. This review aims to evaluate the literature on the ameliorative effects of turmeric extracts and their main components on ethanol toxicity. The relevant studies were identified through searches of Google Scholar, PubMed, and Scopus without any time limitation. The underlying mechanisms of turmeric and curcumin were also discussed. The findings suggest that turmeric and curcumin ameliorate ethanol-induced organ damage by suppressing oxidative stress, inflammation, apoptosis, MAPK activation, TGF-β/Smad signaling pathway, hyperlipidemia, regulating hepatic enzymes, expression of SREBP-1c and PPAR-α. However, the limited clinical evidence suggests that further research is needed to determine the efficacy and safety of turmeric and curcumin in human subjects. In conclusion, the available evidence supports the potential use of turmeric and curcumin as alternative treatments for ethanol toxicity, but further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

Phycocyanin alleviates alcohol-induced testicular injury in male Wistar rats.

Given the noteworthy implications of alcohol consumption and its association with male infertility, there has been a notable focus on investigating natural alternatives to mitigate its adverse effects. Thus, this study was conducted to assess the potential protective effect of phycocyanin extract derived from the blue algae Arthrospira (Spirulina) platensis against ethanol-induced oxidative stress, disturbances in testicular morphology, and alterations in sperm production. Male rats were divided into four groups (five rats each): the control group received a saline solution, the ethanol exposed group (EtOH) was subjected to intraperitoneal injections of 10 mL/kg of ethanol solution at a concentration of 38% (v/v), the phycocyanin alone treated group (P) received oral administration of phycocyanin at a dosage of 50 mg/kg, and the phycocyanin-cotreated group (PE) was given oral phycocyanin followed by ethanol injections. All treatments were administered over a period of 14 days. Our findings demonstrated that ethanol exposure induced reproductive toxicity, characterized by reduced sperm production and viability, alterations in testicular weight and morphology, increased lipid peroxidation levels, and elevated oxidative enzyme activity. In addition, the ethanol-intoxicated group showed perturbations in serum biochemical parameters. However, the simultaneous exposure to ethanol and phycocyanin exhibited a counteractive effect against ethanol toxicity. The results showed that supplementation of phycocyanin prevented oxidative and testicular morphological damage-induced by ethanol and maintained normal sperm production, and viability.

Prevención de úlceras estomacales inducidas por etanol en ratas utilizando extracto de hoja de Senecio perralderianus

Senecio perralderianus belongs to the family of Asteraceae and is only found in Algeria. Some species of this family are used to heal gastrointestinal issues in conventional medicine for their antioxidant and anti-inflammatory properties. This research was performed in order to determine if methanolic extract from the leaves of S. perralderianus had any protective effects on gastroenteritis brought on by alcohol consumption. Wistar rats were fed with 100% ethanol orally to induce gastric ulcer, and pre-treated with 50, 100, and 200 mg·kg-1 of the extract in addition to 5 mg·kg-1 of Ranitidine as a positive reference drug. The extract had shown a positive effect to protect ethanol-induced gastric ulcers with a protection percentage of 71 to 88%. In addition, pretreatment of rats significantly increased levels of GSH, CAT, and SOD in vivo as non-enzymatic and enzymatic antioxidants, and also reduced the level of lipid peroxidation. Histopathological sections, which showed the action of the therapeutic extract, substantially confirmed these findings on the reduction of the inflammation zone and the reduction of immune cell filtration caused by ethanol toxicity with increased extract dosages compared to Ranitidine. The antiulcer activity is due to inhibition of oxidative stress and gastritis. It is associated with a total polyphenol, flavonoids, chlorophyll (a, b), and carotenoids substantial amounts.

Assessment of Oral Acute Toxicity (LD50) of Aqueous, Ethanol, and Acetone Crude Extracts of Plectranthus Neochilus Leaves on Wistar Albino Rats

The Plectranthus genus, comprising more than 300 species distributed through tropical and subtropical areas of Africa, Asia, Oceania and South America, belongs to the Lamiaceae family, which includes some well-established medicinal genus such as mint (Mentha), sage (Salvia) and thyme (Thymus). Toxicology may be defined as the study of harmful, poisonous and adverse effects of drugs and other chemical constituents found in plants, which may increase the chances of mortality or weakness in the general health, physically as well as mentally. Thus, this work was aimed at assessing the oral acute toxicity (LD50) of aqueous, ethanol, and acetone crude extracts of Plectranthus Neochilus Leaves and to establish its safety on wistar albino rats (160-200g) as per OECD guidelines. Lorke’s method (1983) was used for this study. The results of phase one and phase two of the study showed no acute toxicity or mortality in any of the groups of rats in 24 hours, 72 hours and up to two weeks after single oral administration of 10, 100, 1000, 1500, 2250, 3500 and 5000 mg/kg body weight of the animals. In conclusion, oral administration of the plant extracts did not produce any toxic effect in rats. Oral intake of extracts at dose ≤5000 mg/kg body weight is safe, which implies that the oral LD50 is >5000 mg/kg body weight. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

Comparing the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone.

Cocaine is commonly consumed with ethanol, which leads to the formation of cocaethylene through transesterification. Cocaethylene is an active metabolite of cocaine with a longer duration of action. Literature on the combined toxicity of cocaine, ethanol, and cocaethylene is conflicting. We aimed to compare the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone in Hong Kong. This was a retrospective study on acute cocaine toxicities reported to the Hong Kong Poison Control Center from 1 January 2010 to 22 January 2023. Cocaine exposure was confirmed by urine immunoassays/laboratory tests and ethanol co-ingestion was confirmed by blood ethanol concentrations. A serious outcome was defined as a National Poison Data System outcome moderate or above. Univariate analyses and multivariable logistic regression were performed to compare the associations of clinical outcomes with and without ethanol, followed by subgroup analyses of cases with complete data. We analyzed 109 patients (median age 29 years, 71% men, 68% Chinese), of whom 20 had confirmed ethanol co-ingestion (mean blood ethanol concentration 1350mg/L). Multivariable analysis showed that co-exposure to cocaine and ethanol was associated with a lower risk of serious outcomes (adjusted odds ratio 0.09, 95% confidence interval 0.01-0.77; p = 0.03) after adjusting for age, sex, ethnicity, route of cocaine administration, and physical health status. Subgroup analyses showed similar findings. In contrast to previous studies, we did not identify a higher risk of serious outcomes after co-exposure to cocaine and ethanol compared to cocaine alone in a predominantly Chinese cohort.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

Silver decorated nickel oxide nanoflake/carbon nanotube nanocomposite as an efficient electrocatalyst for ethanol oxidation.

The higher energy density and lesser toxicity of ethanol compared to methanol make it an ideal combustible renewable energy source in fuel cells. Finding suitable cost-effective electrocatalysts that can oxidize ethanol in ethanol-based fuel cells is a major challenge. With their high catalytic activity and stability in alkaline media, transition metal-based catalysts are ideal candidates for alkaline direct ethanol fuel cells. Nickel-based nanomaterials and composites exhibit high electrocatalytic activity, which makes them predominant candidates for the electrochemical oxidation of ethanol. In this study, the electrocatalytic activity of a nickel oxide flower-like structure was explored. Forming a nanocomposite of NiO in combination with carbon nanotubes (CNTs), NiO/CNTs, as a substrate led to an increase in the stability of the electrocatalyst in alkaline media. Furthermore, the electrocatalytic activity of the NiO/CNT nanocomposite was greatly enhanced by decorating the surface with different ratios of silver (Ag). Ag/NiO/CNT composites with different Ag ratios, namely, 25% and 50% by weight, were studied. The Ag 25%/NiO/CNT weight ratio showed a maximum ethanol conversion. At an ethanol concentration of 300 mM, the electrochemical oxidation current density was found to be 57.1 ± 0.2 mA cm-2 for the 25% by weight Ag ratio, with a five-fold increase in the current density (compared to NiO/CNTs (10 ± 0.34 mA cm-2)). Furthermore, the nanocomposite synthesized here (Ag 25%/NiO/CNTs) showed a significantly higher energy conversion (current per ethanol concentration) rate compared to other reported NiO-based catalysts. These results open real opportunities for designing high efficiency ethanol fuel cell catalysts.

Insight into the ordering process and ethanol oxidation performance of Au-Pt-Cu ternary alloys.

Direct ethanol fuel cells (DEFCs), which have been widely recognized as nontoxic and green energy conversion devices, show attractive application prospects for liquid hydrogen-carriers, due to the higher specific energy and lower toxicity of ethanol. Pt-based catalysts are widely used in DEFCs, while their poor poisoning resistance highlights the importance of composition and structure optimization. Herein, we synthesized a series of reduced graphene oxide supported ternary alloy AuxPt1-xCu3/rGO (x = 0-1) catalysts with excellent ethanol oxidation performance and a composition-dependent volcano plot trend of the ordering degree was observed and rationalized. The highest Pt-normalized mass activity of Au0.8Pt0.2Cu3/rGO is attributed to the optimized CO binding energy according to DFT calculations. This work not only provides an efficient EOR catalyst based on ordered alloys AuxPt1-xCu3 (x = 0-1), but also offers valuable insight into the role of a third metal in tuning the structure and function of alloys.

Protective Effect of Prosopis Farcta Fruit Aqueous Extract Against Oxidative Stress Caused By Ethanol in Albino Rats

Prosopis farcta was previously used in folk medicine as a dry fruit to relieve pain before its active biological components that contribute to this were known. This study assessed the effectiveness of a dry fruit extract of P. farcta by measuring the indicators of inflammation in albino rats after they were dosed with ethanol. As such, looking at the antioxidant potential of P. farcta fruit aqueous extract (PFFAE) in resistance to ethanol's harm in rats given ethanol showed a notable increase in serum C reactive protein (CRP), malondialdehyde (MDA), CRP/ALB ratio (CAR), and WBC count. At the same time, glutathione peroxidase (GPx) and albumin were markedly reduced. PFFAE diminished ethanol-induced amounts of CRP, MDA, and CAR in plasma; additionally, it strengthened the ethanol-induced decline in GPx activity, and albumin had no apparent effect on the ESR level. Consequently, the current findings demonstrate that PFFAE counteracts the toxicity of ethanol and has a protective impact against the ethanol effect.

Myrrh Attenuates Gonadal Toxicity and DNA Fragmentation Induced by Ethanol in Male Rats

Background: Long-term ethanol consumption causes pathological alterations to the male reproductive system, possibly resulting in infertility. Myrrh is a resin with antioxidant properties that is produced from the bark of Commiphora tree species. This research aimed to observe the protective impact of myrrh extract supplementation on male reproductive injury and toxicity induced by ethanol treatment. Methods: Adult male Sprague Dawley rats were orally treated with 40% ethanol (3 g/kg) in combination with myrrh extract (500 mg/kg) for four weeks to investigate the curative efficiency of myrrh extract against ethanol toxicity from physiological, histopathological and genetic aspects. Result: The findings revealed that the sperm count, testosterone level and DNA concentration diminished significantly in the ethanol-treated rats compared to control rats, while the contents of malondialdehyde (MDA), heat shock protein 70 (HSP70) and proinflammatory mediators, including tumor necrosis factor-α (TNF-α) and nitric oxide (NO), were elevated significantly; severe degenerative changes in the testicular structure and strong testicular DNA fragmentation were also observed. Co-treatment with myrrh attenuated lipid peroxidation and improved testicular histomorphology, testosterone levels and DNA concentrations and pattern, while at the same time, the levels of both HSP70 and TNF-α levels were increased. Our results provide insight into the curative impacts of myrrh on ethanol toxicity resulting from the rich content of curzerene in myrrh, which has antioxidant activities.

Ingestion of 70% Ethanol with Methylene Blue in a Novel Rubbing Alcohol Formulation

Recreational use of sanitizing alcohols, like rubbing alcohol, is a topic every emergency and intensive care Physician should be familiar with. Overindulgence in these substances can lead to ethanol toxicity. However, it's crucial for clinicians to recognize that these products often contain various other chemicals with harmful effects, such as methylene blue. In our analysis of the components of one such product, we present a case report of a patient who experienced alcohol poisoning after consuming it. Fortunately, the patient fully recovered after a brief stay in the intensive care unit. Our conclusion is that the oral ingestion of methylene blue in this product didn't exhibit significant or concerning clinical features. Therefore, the approach to managing such cases should be supportive, akin to dealing with ethanol toxicity.

Investigating the role of lipid genes in liver disease using fatty liver models of alcohol and high fat in zebrafish (Danio rerio).

Accumulation of lipid in the liver is the first hallmark of both alcohol-related liver disease (ALD) and non-alcohol-related fatty liver disease (NAFLD). Recent studies indicate that specific mutations in lipid genes confer risk and might influence disease progression to irreversible liver cirrhosis. This study aimed to understand the function/s of lipid risk genes driving disease development in zebrafish genetic models of alcohol-related and non-alcohol-related fatty liver. We used zebrafish larvae to investigate the effect of alcohol and high fat to model fatty liver and tested the utility of this model to study lipid risk gene functions. CRISPR/Cas9 gene editing was used to create knockdowns in 5 days post-fertilisation zebrafish larvae for the available orthologs of human cirrhosis risk genes (pnpla3, faf2, tm6sf2). To establish fatty liver models, larvae were exposed to ethanol and a high-fat diet (HFD) consisting of chicken egg yolk. Changes in morphology (imaging), survival, liver injury (biochemical tests, histopathology), gene expression (qPCR) and lipid accumulation (dye-specific live imaging) were analysed across treatment groups to test the functions of these genes. Exposure of 5-day post-fertilisation (dpf) WT larvae to 2% ethanol or HFD for 48 h developed measurable hepatic steatosis. CRISPR-Cas9 genome editing depleted pnpla3, faf2 and tm6sf2 gene expression in these CRISPR knockdown larvae (crispants). Depletion significantly increased the effects of ethanol and HFD toxicity by increasing hepatic steatosis and hepatic neutrophil recruitment ≥2-fold in all three crispants. Furthermore, ethanol or HFD exposure significantly altered the expression of genes associated with ethanol metabolism (cyp2y3) and lipid metabolism-related gene expression, including atgl (triglyceride hydrolysis), axox1, echs1 (fatty acid β-oxidation), fabp10a (transport), hmgcra (metabolism), notch1 (signalling) and srebp1 (lipid synthesis), in all three pnpla3, faf2 and tm6sf2 crispants. Nile Red staining in all three crispants revealed significantly increased lipid droplet size and triglyceride accumulation in the livers following exposure to ethanol or HFD. We identified roles for pnpla3, faf2 and tm6sf2 genes in triglyceride accumulation and fatty acid oxidation pathways in a zebrafish larvae model of fatty liver.

Idebenone protects against ethanol toxicity in HT-22 cells through strengthening neuroimmune response

Idebenone, an analogue of coenzyme Q10, may function as a neuroprotective agent with its antioxidant and anti-inflammatory properties. The current report was designed to examine the beneficial effects of idebenone on ethanol-related neurotoxicity in hippocampal neuronal HT-22 cells in vitro and annotate the neuroprotective mechanism of idebenone. 75 mM ethanol was applied to the cells for 24h to develop ethanol toxicity. Then, different concentrations of idebenone (final concentration in the well to be 1, 2.5, and 5 μM) were applied to HT-22 cells for 24 h to explore the protective impact against ethanol-induced hippocampal damage. Cell viability was evaluated with MTT test. MDA, SOD, and GSH concentrations were examined to interpret oxidative damage. Moreover, the effects of idebenone on IL-1β, IL-6, and IL-23 neuroimmune-related genes expression levels were assigned by the RT-PCR analysis. In our study, 75 mM ethanol decreased neuronal cell viability by approximately 61%. All concentrations of idebenone were not toxic to neurons. In addition, idebenone increased cell viability by reducing the damage caused by alcohol. Idebenone reversed the reduction in antioxidant capacity caused by ethanol through decreasing MDA and increasing SOD and GSH levels. In addition, idebenone attenuated ethanol-induced impairment in neuroimmune and neuroinflammatory responses by reducing IL-1β, IL-6, and IL-23 mRNA expression levels. Treatment with idebenone increased antioxidant capacity and a significant improvement was achieved in neuroimmune and neuroinflammatory parameters. Possible mechanisms underlying these beneficial effects cover the down-regulation of IL-1β, IL-6, and IL-23 receptors, and antioxidant restoration of idebenone.

Increased Flux of Lipid Metabolism Enhances Bioethanol Fermentability and Inhibitor Tolerance of Xylose-Utilizing Zymomonas mobilis

The microbial production of fuel ethanol is an attractive and sustainable biotechnological approach. This study presents a metabolic engineering strategy of Zymomonas mobilis aimed at coproducing bioethanol and fatty acids. The increased flux of fatty acids stabilizes the cell membrane and thus counteracts the progressively higher ethanol toxicity. In a glucose medium, the highest ethanol titer achieved was 146.7 g/kg of broth, surpassing the wild-type Z. mobilis CP4 and angel yeast by 30% and 45%, respectively. The recombinant strain exhibited a total fatty acid titer of 0.4 g/L from 230 g/L total sugar solution (5 L bioreactor), representing a 12-fold increase compared to the wild-type Z. mobilis CP4. Furthermore, when using a 4:2:1 mixture of glucose: xylose: mannose (w/v), an ethanol concentration of 142.8 g/kg of broth was attained, only 2.66% lower than that of the glucose-only medium. These findings highlight the enormous potential of this genetically engineered strain for the sustainable production of ethanol and fatty acids from lignocellulosic renewable carbon sources.