Superoxide Dismutase Research Articles

A curcumin-loaded biopolymeric nanocomposite alleviates dextran sulfate sodium induced ulcerative colitis via suppression of inflammation and oxidative stress

Functional drugs nano delivery systems manufactured from natural active products are promising for the field of biomedicines. In this study, an anti-ulcerative colitis (UC) curcumin loaded biopolymeric nanocomposite (CZNH) was fabricated and investigated. CZNH nanocomposite was obtained using the anti-solvent precipitation method, wherein curcumin-loaded zein colloidal particles served as the core, while sodium casein (NaCas) and hyaluronic acid (HA) formed the outermost layer of CZNH nanocomposite. Fourier transform infrared (FT-IR) spectrum and transmission electron microscopy (TEM) findings demonstrated that CZNH nanocomposite was a double-layer spherical micelle (250 nm) resulting from the hydrogen bond interactions and electrostatic adsorptions between zein, NaCas, and HA. Furthermore, CZNH nanocomposite exhibited prominent resuspension and storage stability in aqueous solution, which can be stored at 4 °C for approximately 30 days. In vivo anti-UC studies showed that CZNH nanocomposite could effectively alleviate UC symptoms via mediating inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6], myeloperoxidase (MPO), and oxidative stress factor [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)]. This study suggested that the CZNH nanocomposite showed great promise as an efficient curcumin nanocarrier for UC therapy.

Dermatoprotective effect of Moringa oleifera leaf extract on sodium valproate-induced skin damage in rats

Valproic acid is an antiepileptic drug associated with skin-related issues like excessive hair growth, hair loss, and skin rashes. In contrast, Moringa oleifera, rich in nutrients and antioxidants, is gaining popularity worldwide for its medicinal properties. The protective properties of M. oleifera extract against skin-related side effects caused by valproic acid were investigated. Female rats were divided into control groups and experimental groups such as moringa, sodium valproate, and sodium valproate + moringa groups. A 70% ethanolic extract of moringa (0.3 g/kg/day) was given to moringa groups, and a single dose of sodium valproate (0.5 g/kg/day) was given to valproate groups for 15 days. In the skin samples, antioxidant parameters (such as glutathione, glutathione-S-transferase, superoxide dismutase, catalase, and total antioxidant capacity), as well as oxidant parameters representing oxidative stress (i.e. lipid peroxidation, sialic acid, nitric oxide, reactive oxygen species, and total oxidant capacity), were examined. Additionally, boron, hydroxyproline, sodium-potassium ATPase, and tissue factor values were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also carried out for protein analysis in the skin samples. The results showed that moringa could increase glutathione, total antioxidant capacity, sodium-potassium ATPase, and boron levels, while decreasing lipid peroxidation, sialic acid, nitric oxide, total oxidant capacity, reactive oxygen species, hydroxyproline, and tissue factor levels. These findings imply that moringa possesses the potential to mitigate dermatological side effects.

Growth performance, antioxidant status, intestinal morphology, and body composition of Nile tilapia (Oreochromis niloticus) supplemented with essential oils: A meta-analysis

This study aimed to evaluate the effects of dietary supplementation with essential oils (EOS) on growth performance, antioxidant status in blood serum, intestinal morphology, and whole-body composition of Nile tilapia (Oreochromis niloticus) through a meta-analytic approach. The search and collection of scientific articles were conducted using the PRISMA methodology, and 45 full-text scientific articles were obtained. The data used in the meta-analysis were extracted from these 45 documents. The effect size was assessed through weighted mean differences (WMD) using Der-Simonian and Laird random effects models. Dietary supplementation with EOS increased (P < 0.001) final weight, body weight gain, specific growth rate, feed intake, protein efficiency ratio, and survival but decreased (P < 0.001) feed conversion ratio. In blood serum, EOS supplementation decreased (P < 0.001) the concentration of malondialdehyde and increased (P < 0.001) the concentration of catalase, superoxide dismutase, and glutathione peroxidase. In the foregut, midgut, and hindgut, greater (P < 0.01) villus height, villus width, and number of goblet cells were observed in response to EOS supplementation. EOS supplementation increased (P < 0.01) crude protein content and decreased (P < 0.05) crude lipid content in the whole-body. In conclusion, essential oils can be used as a dietary additive to improve growth performance, antioxidant status in blood serum, and intestinal morphology in Nile tilapia. Likewise, supplementation with essential oils increases the protein content and decreases the fat content in the whole-body of Nile tilapia.

Effect of Persistent Salt Stress on the Physiology and Anatomy of Hybrid Walnut (Juglans major × Juglans regia) Seedlings.

Soil salinization has become one of the major problems that threaten the ecological environment. The aim of this study is to explore the mechanism of salt tolerance of hybrid walnuts (Juglans major × Juglans regia) under long-term salt stress through the dynamic changes of growth, physiological and biochemical characteristics, and anatomical structure. Our findings indicate that (1) salt stress inhibited seedling height and ground diameter increase, and (2) with increasing salt concentration, relative water content (RWC) decreased, and proline (Pro) and soluble sugar (SS) content increased. The Pro content reached a maximum of 549.64 μg/g on the 42nd day. The increase in superoxide dismutase (SOD) activity (46.80-117.16%), ascorbate peroxidase (APX) activity, total flavonoid content (TFC), and total phenol content (TPC) under salt stress reduced the accumulation of malondialdehyde (MDA). (3) Increasing salt concentration led to increases and subsequent decreases in the thickness of palisade tissues, spongy tissues, leaves, and leaf vascular bundle diameter. Upper and lower skin thickness, root periderm thickness, root diameter, root cortex thickness, and root vascular bundle diameter showed different patterns of change at varying stress concentrations and durations. Overall, the study concluded that salt stress enhanced the antireactive oxygen system, increased levels of osmotic regulators, and low salt concentrations promoted leaf and root anatomy, but that under long-term exposure to high salt levels, leaf anatomy was severely damaged. For the first time, this study combined the anatomical structure of the vegetative organ of hybrid walnut with physiology and biochemistry, which is of great significance for addressing the challenge of walnut salt stress and expanding the planting area.

The Hepatoprotective Effect of Glycyrrhiza glabra Roots Extract Against Amiodarone Induced Hepatotoxicity in Male Rats

Amiodarone (AMD), a powerful antidysrhythmic medication, can cause hepatotoxicity when used long-term or in high doses. It affects both mitochondrial and lysosomal function because of its lipophilic nature and accumulation in tissues. It also has direct production of ROS. Glycyrrhiza glabra is one of the medicinal plants that have been commonly used for thousands of years. It possesses anti-ulcer, anti-inflammatory and antioxidant properties. In this study, the antihepatotoxic effect of Gg was evaluated against AMD liver toxicity in rats model, thirty rats were taken and divided evenly into five groups given daily doses by gastric gavage oral tube for 3 weeks as follows: the 1st group acted as a control group given D.W., and the 2nd group received AMD at a dose of 300mg/kg for 2 weeks. 3rd, 4th, and 5th groups were pretreated with Gg in doses of 200, 400, and 800 mg, respectively, for one week, then along with AMD for 2 weeks. Hepatic damage, revealed by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum phospholipase A2 (PLA2) was decreased in the AMD group. Gg extract significantly reduced the elevated AST and ALT levels caused by AMD intoxication, rendering PLA2 to its normal level. It also enhanced liver superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. Gg extract markedly reverses the increased serum TNF levels induced by AMD; therefore, it may be considered a good hepatoprotective agent.

Lactobacillus rhamnosus NKU FL1-8 Isolated from Infant Feces Ameliorates the Alcoholic Liver Damage by Regulating the Gut Microbiota and Intestinal Barrier in C57BL/6J Mice.

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.

Drought stimulus enhanced stress tolerance in winter wheat (Triticum aestivum L.) by improving physiological characteristics, growth, and water productivity

The impact of drought events on the growth and yield of wheat plants has been extensively reported; however, limited information is available on the changes in physiological characteristics and their effects on the growth and water productivity of wheat after repeated drought stimuli. Moreover, whether appropriate drought stimulus can improve stress resistance in plants by improving physiological traits remains to be explored. Thus, in this study, a pot experiment was conducted to investigate the effects of intermittent and persistent mild [65%–75% soil water-holding capacity (SWHC)], moderate (55%–65% SWHC), and severe drought (45%–55% SWHC) stress on the growth, physiological characteristics, yield, and water-use efficiency (WUE) of winter wheat. After the second stress stimulus, persistent severe drought stress resulted in 30.98%, 234.62%, 53.80%, and 31.00% reduction in leaf relative water content, leaf water potential, photosynthetic rate (Pn), and indole-3-acetic acid content (IAA), respectively, compared to the control plants. However, abscisic acid content, antioxidant enzyme activities, and osmoregulatory substance contents increased significantly under drought stress, especially under persistent drought stress. After the second rehydration stimulus (ASRR), the actual and maximum efficiency of PSII and leaf water status in the plants exposed to intermittent moderate drought (IS2) stress were restored to the control levels, resulting in Pn being 102.56% of the control values; instantaneous WUE of the plants exposed to persistent severe drought stress was 1.79 times that of the control plants. In addition, the activities of superoxide dismutase, peroxidase, catalase, and glutathione reductase, as well as the content of proline, under persistent mild drought stress increased by 52.98%, 33.47%, 51.95%, 52.35%, and 17.07% at ASRR, respectively, compared to the control plants, which provided continuous antioxidant protection to wheat plants. This was also demonstrated by the lower H2O2 and MDA contents after rehydration. At ASRR, the IAA content in the IS2 and persistent moderate drought treatments increased by 36.23% and 19.61%, respectively, compared to the control plants, which favored increased aboveground dry mass and plant height. Compared to the control plants, IS2 significantly increased wheat yield, WUE for grain yield, and WUE for biomass, by 10.15%, 32.94%, and 33.16%, respectively. Collectively, IS2 increased grain growth, yield, and WUE, which could be mainly attributed to improved physiological characteristics after drought-stimulated rehydration.

P-266 Profiling redox effects induced by micro-nanoplastics in the female reproductive system: insights from human granulosa cells

Abstract Study question Are nano-microplastics (NMPs) taken up into human granulosa cells causing redox alterations? Summary answer NMPs enter into human granulosa cells and influence viability, energy production and antioxidant response. What is known already In recent decades, anthropogenic activities have increased the production of global plastic with millions of tons produced every year. Under the action of different physical, chemical or biological agents, plastic waste breaks down into (NMP) particles that propagate in the environment posing threats for human health. NMPs translocate from digestive tract to circulatory systems reaching organs and cells, including female gonads. Nevertheless, there is insufficient knowledge of their effects on reproductive functions in mammals to allow for an accurate risk assessment to be conducted and any risks managed in animal and human being contexts. Study design, size, duration Human ovarian granulosa cells (KGN cell line) were exposed to NMPs of different sizes (40 nm, 70 nm, 100 nm, and 200 nm) at concentrations ranging from 5 to 1000 μg/ml for 24 h and then processed for cellular and biochemical analyses Participants/materials, setting, methods NMPs uptake by granulosa cells was tested by the employment of fluorescent NMPs and observation under confocal laser scanning microscopy. Cell viability was assed by Cell Counting Kit8. The effects of NMPs on mitochondrial bioenergetics was evaluated by MitoStress kit (Seahorse Xfe96, Agilent). ATP production was evaluated by Cell Titer-Glo ATP assay kit (Promega). Key enzymes of antioxidant response were analysed at transcript and protein level by using real-time Taqman PCR and Western blotting, respectively. Main results and the role of chance We demonstrated that NMPs are taken up by granulosa cells at all tested concentrions along with significant decrease of cell vitality with all sizes and concentrations. Seahorse analysis revealed an altered bioenergetic profiles. ATP levels increase at 70, 100 and 200 nm (one way ANOVA p = 0.001) at all tested concentrations (one way ANOVA p &amp;lt; 0.001). The gene and protein expression of catalase (CAT) superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) increased at 5 and 100 µg/ml with all sizes except 100 nm, whereas the level of sirtuins (SIRT1 and SIRT3) transcripts and protein decreased. Reduced levels of phosphorylated NRF2, the transcription factor that activates antioxidant responsive elements (ARE)-mediated gene expression were observed. Limitations, reasons for caution The use of human cell lines requires careful consideration when transferring to human testing. Wider implications of the findings Our results contribute to understanding the effects of NMPs on mammalian fertility in order to find possible protective approaches. Considering that the level of susceptibility of mammalian female germ cells to NMPs is still unknown, present results contribute to evidence-based strategies allowing living and working in a health promoting environment. Trial registration number Effects of combined exposure to nano/microplastics and plastic additives on mammalian female fertility (CUP E53D2301100006)

Anti‑epileptic mechanism of isopimaric acid from Platycladi cacumen based on network pharmacology, molecular docking and biological validation.

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti-epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti-epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)-induced murine microglial cell line (BV2) was used to confirm anti-epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood-brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS-induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti-oxidative enzymes (superoxide dismutase-1 and -2) and suppressed inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti-epileptic compound derived from PC.

Preclinical antidiabetic and antioxidant effects of Erythrophleum africanum (benth.) harms in streptozotocin-induced diabetic nephropathy.

This study investigated the antidiabetic effects of the methanolic extract of E.africanum (MEEA) stem bark on streptozotocin (STZ)-induced diabetic nephropathy (DN) in Wistar rats. The invitro enzyme (α-amylase) inhibitory activity of MEEA was measured using a standard procedure. Diabetic rats with fasting blood glucose above 250 mg/dL were considered diabetic and were divided intothe following groups: control (distilled water-treated), diabetic-control, diabetic metformin (100 mg/kg), diabetes + MEEA (150 mg/kg), and diabetes + MEEA (300 mg/kg) via oral gavage once daily for 14days. At the end of the experimental period, kidney tissues were collected for biochemical and histological analyses. Kidney apoptosis and marker gene expression were measured by real-time quantitative PCR. MEEA exhibited α-amylase inhibitory effects. MEEA significantly (p<0.05) reduced the STZ-induced increases in blood glucose, serum urea, serum creatinine, uric acid, alanine aminotransferase, alkaline phosphatase, and malondialdehyde and increased the STZ-induced decreases in superoxide dismutase, catalase, and reduced glutathione. In addition, MEEA protects against DN by significantly downregulating the mRNA expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response binding protein (CREB), and cFOS and upregulating B-cell lymphoma 2 (Bcl-2), suggesting that the nephroprotective ability of MEEA is due to the modulation of the cAMP/PKA/CREB/cFOS signaling pathway. Furthermore, MEEA treatment protected against histopathological alterations observed in diabetic rats. The data from this study suggest that MEEA modulates glucose homeostasis and inhibits redox imbalance in DN rats.

P-002 Acetate attenuates cyclophosphamide-induced testicular toxicity by modulating steroidogenic and apoptotic signaling via an oxidative stress-dependent pathway

Abstract Study question Will acetate therapy attenuate cyclophosphamide-induced testicular toxicity when used concomitantly? Summary answer Acetate attenuated cyclophosphamide-induced testicular toxicity by modulating steroidogenic and apoptotic signaling via an oxidative stress-dependent pathway. What is known already Cyclophosphamide is an anthracycline that is effective in the management of cancers. Nonetheless, a major drawback of this drug is its testicular toxicity. Available evidence in the literature revealed that cyclophosphamide induces testicular toxicity by targeting steroidogenesis and activating oxidative stress, inflammation, and apoptosis. On the other hand, acetate has been reported to exert antioxidant, anti-inflammatory, and anti-apoptotic activities. However, there is no report on the effect of acetate on cyclophosphamide-induced testicular toxicity. Study design, size, duration This is a prospective experimental study using animal model. Twenty-four sexually mature litter-mate male Wistar rats of comparable weight were used for the study. The study lasted 2 weeks. Participants/materials, setting, methods Animals were acclimatized for two weeks, and then randomized into four groups. The control rats received 0.5mL of distilled water p.o for 14 days, acetate-treated rats received 200 mg/kg/day of acetate p.o for 14 days, cyclophosphamide-treated rats received 150 mg/kg of cyclophosphamide i.p on day 8, while acetate + cyclophosphamide-treated rats received treatment as acetate-treated and cyclophosphamide-treated. The doses of drugs used were the Human Equivalent doses for rats and as earlier reported. Main results and the role of chance Acetate attenuated cyclophosphamide-induced alterations in testicular histoarchitecture and the rise in testicular activities of gamma glutamyl transferase and lactate dehydrogenase activities, and lactate levels. In addition, acetate abrogated cyclophosphamide-induced rise in testicular malondialdehyde, TNF-α, IL-1β, NF-kB, and Bax levels, and myeloperoxidase, caspase 9, and caspase 3 activities, which was accompanied by acetate-driven blockade of cyclophosphamide-induced decline in reduced glutathione, Nrf2, and Bcl-2 levels, and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase activities. Furthermore, acetate alleviated cyclophosphamide-induced suppression of circulatory levels of FSH, LH, and testosterone, testicular concentrations of 3β-HSD, 17β-HSD, and testosterone, and spermatogenesis and lowered sperm quality. Limitations, reasons for caution This was an experimental study using a rat model; hence, the results of this study should be extrapolated to humans with caution. Clinical trials are recommended to validate these findings. Wider implications of the findings The present study revealed the protective effect of acetate treatment on cyclophosphamide-induced testicular toxicity. These findings provide convincing evidence of the attenuating effect of acetate in cyclophosphamide-induced testicular toxicity. Trial registration number N/A

P-104 Cytoprotective effect of melatonin in prepubertal Sertoli cells: role in cadmium-induced idiopathic male infertility

Abstract Study question Melatonin (MLT) is a cytoprotective agent holding potential to prevent cadmium (Cd) toxicity and its impact in testicular function and fertility. Summary answer MLT produced a potent cytoprotective effect in Sertoli cells (SCs) exposed to Cd-toxicity, reducing its H2O2 generation and reductive stress effects by modulation Nrf2 activity. What is known already MLT a hormonal substance exhibiting strong antioxidative and antiapoptotic properties, has been proved to hold great potential as cytoprotec tive agent in a range of tissues and cell models exposed to Cd toxicity, including the rat bone, ovaries, human MSC, and even mammalian testes. However, cellular and mechanistic aspects of this effect of MLT in testes remain poorly understood. Cd is a pro-oxidant heavy metal reported to interfere with testicular function and fertility. Both the toxicity of Cd and the cytoprotective function of MLT involve redox-dependent mechanisms with the activity of Nrf2 transcription factor as key player on the cellular stress response. Study design, size, duration Porcine pre-pubertal SCs were maintained at 37 °C in a 5% CO2 humidified atmosphere in the absence (unexposed-control group) or presence of 5 or 10µM CdCl2 (Sigma Chemical Co.) and/or 50nM MLT (Sigma-Aldrich) for 48h in HAMF12 (Euroclone) supplemented with 0.166nM retinoic acid (Sigma-Aldrich Co.) and 5/500ml of Insulin-Transferrin-Selenium (ITS) + Premix (Cat. No. 354352; Corning). Participants/materials, setting, methods After treatment the parameters investigated in the study were: a) SCs viability (MTT test); b) SCs functionality parameters AMH and inhibin B. (real-time PCR and ELISA analysis); c) Intracellular and extracellular ROS production ( with Amplex Red and DCFH-DA fluorescent probe respectively); d) Catalase enzyme activity (spectrophotometric assay procedure); e) Nrf2 and other transcription factors (by semi-quantitative microplate confocal microscopy analysis); f) Intracellular and extracellular levels of GSH and other thiols (by HPLC); g) c-Jun and ERK1/2 (Immunoblot). Main results and the role of chance MLT co-treatment significantly prevented the effects of Cd on cell viability and abnormal ROS production. The reduction of H2O2 efflux was very important and combined with an increased CAT activity that was demonstrated upon MLT treatment significantly in SCs exposed to 5μMCd. The co-treatment with MLT compared to Cd treatment, showed a trend toward a significant recovery of AMH and inhibin B gene expression and secretion levels, respectively, demonstrating the cytoprotective effect of MLT in SCs exposed to Cd toxicity at the functional level. In Cd-treated cells, MLT significantly reduced the expression and nuclear translocation of Nrf2 protein, and decreased GSTP induction. However, MLT reduced Cys uptake and stimulated GSH efflux when the cells were treated with 10 µM Cd, suggesting a specific role for the Nrf2-GSTP axis in the cytoprotective response to MLT of Cd-treated SCs. Finally MLT induced MAPK-ERK1-2 pathway and c-Jun transcription factor when the cells were treated with Cd. MLT is a cytoprotective agent in SCs exposed to Cd toxicity capable to restore cell viability and function. Its activity is associated with the modulation of Nrf2 and other stress response genes important in the control of thiols and H2O2 metabolism of SCs, including cJun and MAPKs. Limitations, reasons for caution Other ROS-scavenging genes other than CAT may have a role in the antioxidant response to MLT of SCs, such as superoxide dismutase, glutathione peroxidases, and peroxyredoxins that are worth investigating further. Wider implications of the findings The aspects that emerged from our study and, described for the first time in these cells, warrant further preclinical and clinical investigation holding potential in the treatment of Cd-induced testicular damage and fertility problems. Trial registration number Not applicable

Protective Effects of Stem Cells and Vitamin D3 Against Hepatic Ischemia/Reperfusion Injury in Rats

Abstract Background Liver transplantation is one of the most efficient life-saving treatments for various end-stage hepatic diseases. However, hepatic ischemic reperfusion injury (IRI) remains a major problem in liver surgeries morbidities and mortalities. Stem cells (SCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine, including liver diseases. Aim to investigate the effect of vitamin D and Bone Marrow Mesenchymal Stem Cells (BM- MSCs) solely or combined on hepatic IR injury. Methods Sixty adult male Wister rats were allocated into 5 groups; Sham, IR: underwent hepatic IR, vit. D-IR: received vit. D in a dose of 500 IU/Kg/day, by gavage, 5 days/week for 2 weeks, then subjected to hepatic IR, Stem cell-IR: received single IV injection of 1 × 106 BM-MSCs prior to hepatic IR and Combined-IR: received both vit. D and BM-MSCs prior to hepatic IR. All rats were subjected to estimation of Liver index (LI), assessment of serum levels of alanine, aspartate transaminases (ALT, AST) and vitamin D, hepatic tissue levels of Malondialdehyde (H.MDA), Superoxide dismutase (H.SOD), Interleukin-2, 10 (H.IL-2, H.IL-10), Caspase-3 (H.Casp-3), H.LC3B and hepatocyte growth factor (H.HGF), as well as histopathological liver examination and scoring. Results Hepatic IR resulted in significant elevation of ALT, AST and H.MDA, H.IL-2, H. Casp- 3 as well as significant reduction in LI, vit. D, H.SOD, H.IL-10, H.LC3B and H.HGF with evident hepatic sinusoidal congestion, cytoplasmic vacuolation and cellular necrosis. Treatment either solely or in combination mitigate these changes with the combined treatment showed the best results compared to the individual use. Conclusion In vivo coadministration of vitamin D and BM-MSCs prior to hepatic IR attenuated hepatocellular damage through preventing oxidative stress and inflammatory response, augmenting autophagic, regenerative capacity and anti-apoptotic effect.

Effect of Orchidectomy on Hepatic Ischemia/Reperfusion Injury

Abstract Background Little attention has been paid to investigate the effect of orchidectomy on hepatic ischemia/reperfusion (I/R) injury, which is lacking. The Aim of This Study is to evaluate the possible impact of orchidectomy and/or testosterone treatment on the function and structure of liver in rat model of hepatic I/R injury and, also, to explore the possible underlying mechanism(s). Materials and Methods 65 male Wistar albino-rats were divided into 5 groups; sham- operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone- treated hepatic ischemia/reperfusion group (T+I/R) and Orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α) and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. Results Hepatic I/R was associated with significant rise of serum ALT and AST, and hepatic tissue TNF-α, NF-κB and MDA, and significant reduction of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2. Histopathological analysis showed vacuolization of the cytoplasm, dilated sinusoids, inflammatory cells infiltration, increased collagen fibers and significantly increased caspase-3. Hepatic I/R -mediated effects were aggravated following orchidectomy, however preischemic treatment with testosterone protected the liver as shown by the significant decline in ALT and AST, and hepatic tissue MDA, TNF-α and NF-κB, and significant enhancement of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2, and restoration of hepatic architecture. Conclusion Orchidectomy hypersensitizes the liver to ischemic injury, due to exaggeration of oxidative and inflammatory states and apoptosis, while testosterone treatment improved the hepatic I/R detrimental effects on liver function and morphology due to its suppressive effect on oxidative and inflammatory states and apoptosis.

P-100 Prolonged exposure to polyethylene glycol (peg) 6000 severely affects the reproductive system of male Wistar rats

Abstract Study question Studies have shown that microplastics have adverse effects on aquatic reproductive health. Is there any potential effect of Polyethylene glycol (PEG)6000 on rodents reproductive system? Summary answer Despite its wide use in industry, medicine and cosmetic formulations, prolonged exposure to PEG 6000 may pose great risk, especially causing reproductive toxicity. What is known already The usage of Polyethylene glycol (PEG) 6000, a microplastic, is rising in industries, medicine, and cosmetic formulations. They serve as ointment bases, capsules, liquid prescription, suppositories and recently used to alleviate constipation. More so, it is one of the pivotal ingredients in soaps, detergents, and also used as chemical intermediates in textile, leather and plastic industries. Additionally, PEG 6000 is widely used in drug delivery systems and tissue engineering. Although approved for internal consumption by regulatory agencies like FDA, there are evidences of its developmental toxicity. Study design, size, duration Fifteen(15) rats weighing between 200-250g were used in this study. The rats were divided into three groups(A, B and C), of 5 rats in each group. Group A was designated as the control group while groups B and C were the test groups. Group A received distilled water, while groups B and C were administered 50 mg/kg and 200 mg/kg body weight of polyethylene glycol PEG6000 respectively via oral gavage daily for 6 weeks. Participants/materials, setting, methods After 6 weeks, the rats were sacrificed as reproductive organs and serum obtained. Enzyme immunosorbent assay (ELISA) was used for hormonal assays. Reproductive organs were weighed and tissue damage was determined using Haemoxylin /eosin staining. Antioxidant enzymes levels (Catalase, Superoxide dismutase), Glutathione peroxidise) and Lipid peroxidation (Malondialdehyde) were also evaluated. Computer-assisted sperm assay (CASA) was used to evaluate sperm parameters and sperm movement kinetics. Main results and the role of chance PEG 6000 caused a reduction in the weights of the rats in groups B and C when compared with control group. There was no significant change in the relative testicular and seminal vesicle organ/body weight ratio in groups B and C, however a pattern of reduction was seen in the organ/body weight ratio of epididymis and prostate, when compared to control group. Serum hormonal levels of Follicle stimulating hormone and Luteinizing hormone were reduced in the test groups when compared to control, but not significant. Testosterone was significantly reduced in groups B and C, while estradiol levels were significantly elevated in groups B and C when compared to control group. There was significant reduction in the levels of Superoxide dismutase, Catalase and Glutathione peroxidase, and a significant increase in Malondialdehyde levels in groups B and C when compared to the control group. Histopathological changes were also seen in the testes, epididymis, seminal vesicles and prostate glands of rats in the test groups. Semen analyses showed statistically significant reductions (p &amp;lt; 0.05) in sperm concentration, motility, vitality and sperm movement kinetics of rats in the test groups when compared to the control group. Limitations, reasons for caution Although this study was done in rats, it may not be easy to extrapolate the present findings to humans. However, this calls for caution as primates and rodents are both members of the superorder Euarchontoglires. Wider implications of the findings Prolonged ingestion of PEG 6000 affects male reproductive system, alters hormonal levels, reduces sperm parameters and induces oxidative stress. Interestingly, the disruptive effects of PEG 6000 are dose-dependent, and may lead to male infertility. Trial registration number not applicable

Trehalose Protects against Superoxide Dismutase 1 Proteinopathy in an Amyotrophic Lateral Sclerosis Model

This work aimed to study the effect of trehalose in protecting cells against Sod1 proteinopathy associated with amyotrophic lateral sclerosis (ALS). Humanized yeast cells in which native Sod1 was replaced by wild-type human Sod1 or an ALS mutant (WT-A4V Sod1 heterodimer) were used as the experimental model. Cells were treated with 10% trehalose (p/v) before or after the appearance of hSod1 proteinopathy induced by oxidative stress. In both conditions, trehalose reduced the number of cells with Sod1 inclusions, increased Sod1 activity, and decreased the levels of intracellular oxidation, demonstrating that trehalose avoids Sod1 misfolding and loss of function in response to oxidative stress. The survival rates of ALS Sod1 cells stressed in the presence of trehalose were 60% higher than in their absence. Treatment with trehalose after the appearance of Sod1 inclusions in cells expressing WT Sod1 doubled longevity; after 5 days, non-treated cells did not survive, but 15% of cells treated with sugar were still alive. Altogether, our results emphasize the potential of trehalose as a novel therapy, which might be applied preventively in ALS patients with a family history of the disease or after diagnosis in ALS patients who discover the disease following the first symptoms.

Mitigation of Abiotic Stresses in Plants through Nutrient Management

The food demand over the world is increasing due to the rapid increase in the population. Direct and indirect effects of climate change have severely affected the growth and development of crops. Of these, abiotic stress factors are reported to cause a reduction in crop productivity ranging from 51 percent to 82 percent. Abiotic stresses like drought, waterlogging stress, salt stress, soil acidity, metal toxicities and temperature variations have overwhelming impact on the growth and productivity of crops. Abiotic stress causes increase in reactive oxygen species (ROS) levels and affects various physiological processes, causing reduction in plant growth and yield. Nutrient management proves to be an effective strategy for alleviating various abiotic stress factors affecting agricultural crops. Nutrients such as nitrogen, potassium, calcium and magnesium increase the production of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase and reduces ROS production. Micronutrients such as iron, boron and zinc as well as biofertilizers improve plant adaptation to various stresses through activation of antioxidant enzymes. Current review focuses on the impact of mineral nutrients, organic amendments and biofertilizers in alleviating abiotic stress in agricultural crops.

Hematological and neurological impact studies on the exposure to naturally occurring radioactive materials

Naturally Occurring Radioactive Materials (NORM) contribute to everyone's natural background radiation dose. The technologically advanced activities of the gas and oil sectors produce considerable amounts of radioactive materials as industrial by-products or waste products. The goal of the current study is to estimate the danger of long-term liability to Technologically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) on blood indices, neurotransmitters, oxidative stress markers, and β-amyloid in the cerebral cortex of rats' brains. Twenty adult male albino rats were divided into two equal groups (n = 10): control and irradiated. Irradiated rats were exposed to a total dose of 0.016 Gy of TE-NORM as a whole-body chronic exposure over a period of two months. It should be ''The results showed no significant changes in RBC count, Hb concentration, hematocrit percentage (HCT%), and Mean Corpuscular Hemoglobin Concentration (MCHC). However, there was a significant increase in the Mean Corpuscular Volume of RBCs (MCV) and a significant decrease in cell distribution width (RDW%) compared to the control. Alteration in neurotransmitters is noticeable by a significant increase in glutamic acid and significant decreases in serotonin and dopamine. Increased lipid peroxidation, decreased glutathione content, superoxide dismutase, catalase, and glutathione peroxidase activities indicating oxidative stress were accompanied by increased β-amyloid in the cerebral cortex of rats' brains. The findings of the present study showed that chronic radiation liability has some harmful effects, that may predict the risks of future health problems in occupational radiation exposure in the oil industries. Therefore, the control of exposure and application of sample dosimetry is recommended for health and safety.

Protective Role of Ellagic Acid Against Ethanol-Induced Neurodevelopmental Disorders in Newborn Male Rats: Insights into Maintenance of Mitochondrial Function and Inhibition of Oxidative Stress.

Ellagic acid (EA) exerts, neuroprotective, mitoprotective, anti-oxidative and anti-inflammatory effects. We evaluated protective effect of EA on ethanol-induced fetal alcohol spectrum disorders (FASD). A total of 35 newborn male rats were used, divided into five groups, including; control (normal saline), ethanol (5.25 g/kg per day), ethanol (5.25 g/kg per day) + EA (10 mg/kg), ethanol (5.25 g/kg per day) + EA (20 mg/kg) and ethanol (5.25 g/kg per day) + EA (40 mg/kg). Thirty-six days after birth behavioral tests (Morris water maze and Elevated Plus Maze), tumor necrosis factor-α (TNF-α) levels, oxidative markers (malondialdehyde, glutathione and superoxide dismutase), mitochondrial examination such as succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) formation were analyzed. The results revealed that ethanol exposure adversely affected cognitive and mitochondrial functions and as well as induced oxidative stress and inflammation in brain tissue. However, EA (20 and 40 mg/kg) administration effectively prevented the toxic effects of ethanol in FASD model. These findings demonstrate that ethanol application significantly impairs the brain development via mitochondrial dysfunction and induction of oxidative stress. These data indicate that EA might be a useful compound for prevention of alcohol-induced FASD.

Characterization of Physiological and Biochemical Attributes of Neem (Azadirachta indica A. Juss) under Salinity Stress

Salinity poses a significant threat to agricultural productivity worldwide, with its detrimental effects on plant growth and physiological processes. Understanding the mechanisms by which plants respond to salt stress is crucial for developing strategies to mitigate its impact on crop yield and sustainability. To address this issue, a pot study was conducted to determine the effect of salt stress on the physiological and biochemical attributes of neem (Azdiarchta indica A. Juss). Plants were grown for 10 months in pots filled with soil having different salinity levels of 3, 6, 9, 12, 15, and 18 dS m−1 and compared with a control of 1.7 dS m−1. The results showed that plant growth and chlorophyll contents declined as salinity levels increased. Due to oxidative stress, the contents of H2O2 increased under higher salt levels. The mitigation of oxidative stress was achieved through the activation of antioxidant enzymes (catalase, ascorbate peroxidase, peroxidase, and superoxide dismutase). Multivariate analysis indicated that Na+ accumulation in plants was positively related to H2O2 production and enzymatic activities, and negatively related to plant biomass, chlorophyll contents, root and shoot K+ concentration, and root K+/Na+. The experimental results suggest that neem plants can be grown in moderate saline soils.