Levels Of Anti-inflammatory Cytokines Research Articles

Gallic acid exerts protective effects in spinal cord injured rats through modulating microglial polarization

BackgroundSpinal cord injury (SCI) is a highly traumatic injury that causes mechanical damage to the spinal cord. Our study aimed to investigate whether gallic acid has protective effects against SCI injury. MethodsAdult male rats were subjected to contusive spinal cord injuries. For behavioural evaluation, the rats were given gallic acid by i.p. injection at the doses of 10, 50 or 100 mg/kg immediately after SCI once daily for consecutive 28 days. Behavioral tests were used to evaluate locomotor functions, mechanical sensitivity and nerve conduction functions. For biochemical experiments, the rats were randomly divided into three groups: sham group, SCI group and SCI+gallic acid group. The rats in the SCI+gallic acid group were given gallic acid at the dose of 100 mg/kg immediately after SCI once daily for consecutive 14 days. The levels of inflammatory factors were evaluated. ResultsGallic acid treatment could improve locomotive and sensory function and reduce the functional impairments in SCI rats. The effects were more effective with increasing gallic acid dose. The levels of M1 markers (inducible nitric oxide synthase and cyclooxygenase-2) were decreased in gallic acid-treated SCI rats, whereas the levels of M2 markers (arginase 1 and cluster of differentiation 206) were increased in response to gallic acid administration. Gallic acid treatment resulted in a significant reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokine levels. ConclusionGallic acid enhances the recovery in SCI rats by regulating microglial polarization. The underlying mechanism may involve the promotion of M2 polarization and the suppression of M1 polarization in microglia.

Impacts of different triathlon races on systemic cytokine profile and metabolic parameters in healthy individuals: a systematic review

The present systematic review aimed to discuss the impacts of different triathlon protocols on the level of pro and anti-inflammatory cytokines, as well as biomarkers related to the performance of healthy individuals. Four databases [PubMed (28 articles), Scopus (24 articles), Science Direct (200 articles), and SPORT Discus (1101 articles) were assessed. The eligibility criteria were applied, and the selected articles were used in the peer review, independently, as they were identified by March 2022. Of the 1359 articles found, 10 were included in this systematic review. Despite the difference in triathlon protocols, it was observed an increase in pro and anti-inflammatory cytokines including IL-4 and IL-10, and chemokines, such as IL-8 and MCP-1. Moreover, the anti-inflammatory serum levels increase after triathlon. Overall, the studies also reported enhancement in the serum levels of cortisol, creatine kinase, C reactive protein, Endothelial Growth Factor, Vascular Endothelial Growth Factor, Myostatin, Lactate dehydrogenase, free fatty acids, and lactate dehydrogenase in triathlon athletes. This systematic review indicates that different triathlon race promotes an acute elevation of circulating cytokines and chemokines levels which return to standard levels after triathlon races. The findings of this systematic review demonstrate that the modulation of inflammatory parameters may be associated with an increase in metabolic indicators (CK, Cortisol, and LDH) after the end of different types of triathlon races.

Synaptamide modulates glial and neurotransmitter activity in the spinal cord during neuropathic pain

N-docosahexaenoylethanolamine, or synaptamide, is an endogenous metabolite of docosahexaenoic acid that is known for synaptogenic and neurogenic effects. In our previous studies we have shown that synaptamide attenuates neuropathic pain, facilitates remyelination, and reduces neuroinflammation after the chronic constriction injury (CCI) of the sciatic nerve in rats. In the current study, we show that daily synaptamide administration (4 mg/kg/day) within 14 days post-surgery: (1) decreases micro- and astroglia activity in the dorsal and ventral horns of the lumbar spinal cord; (2) modulates pro-inflammatory (IL1β, IL6) and anti-inflammatory (IL4, IL10) cytokine level in the serum and spinal cord; (3) leads to a rise in synaptamide and anandamide concentration in the spinal cord; (4) enhances IL10, CD206 and N-acylethanolamine-hydrolyzing acid amidase synthesis in macrophage cell culture following LPS-induced inflammation. Thus, the ability of synaptamide to modulate glial and cytokine activity indicates its potential for implementation in the treatment peripheral nerve injury.

“Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats”

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.

Titanium dioxide E171 consumption exacerbates Listeria monocytogenes infection in mice

Abstract The food additive titanium dioxide is commonly utilized to enhance the appearance and flavor of food products. However, this substance has been linked to gastrointestinal disorders. The aim of this study was to investigate the impact of dietary exposure of titanium dioxide E171 on Listeria monocytogenes infection in mice. Mice were mainly divided into the control, LM group (L. monocytogenes infection), and E171+LM groups (E171 supplementation before L. monocytogenes infection). Pre-exposure to E171 resulted in increased bacterial counts in the liver, spleen, ileum, colon, mesenteric lymph nodes, and feces of mice after L. monocytogenes infection. Moreover, E171 exposure increased the levels of pro-inflammatory cytokines while attenuating the levels of anti-inflammatory cytokines in mice infected with L. monocytogenes. Meanwhile, mice in the E171+LM group exhibited considerably more severe colonic inflammation and worse intestinal barrier function than mice in the LM group. The 16S rRNA gene sequencing revealed a shift in the composition of the gut microbiota of mice in the E171+LM group, characterized by a decrease in the relative abundance of Firmicutes and a decrease in the Firmicutes-to-Bacteroidetes ratio. The levels of acetate, butyrate, and isobutyrate were markedly decreased within the cecum of mice in the E171+LM group in comparison to mice in the LM group. In conclusion, these results suggest that E171 exposure could exacerbate L. monocytogenes infection in mice, which may provide useful information for future risk assessment of this commonly used food additive.

The Positive Effect of Atropa belladonna on Inflammatory Cytokines in the Animal Model of Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and demyelination of the central nervous system. Given the role of inflammation in the pathogenesis of MS and the anti-inflammatory effect of Atropa belladonna (AB), the aim of this study was to determine the effect of AB on inflammatory and anti-inflammatory factors in MOG35-55 induced experimental autoimmune encephalomyelitis (EAE). Methods: Thirty-two purebred C57BL/6 mice, weighing (20±2g) were randomly assigned to the 4 groups: control, and three experimental groups: EAE, EAE+AB100, and EAE+AB300 that after EAE induction received 0, 100, and 300 mg/kg AB daily. AB was dissolved in PBS (phosphate-buffered saline) and the volume of gavage in all groups was 100 µL. After 30 days, the mice were weighed, anesthetized with ether and blood was collected directly from the heart. Specific animal ELISA kits measured the inflammatory cytokines (IL-10, IL-17, IL-4, and TNF-α). One-way ANOVA with Duncan post hoc test was used for comparison between groups. Results: EAE increased serum concentrations of TNF-α, IL-17, and decreased IL-10 and IL-4 compared to the control group. AB significantly decreased the mean level of TNF-α, IL-17 and increased IL-10 and IL-4 compared with EAE group. The effect of 300 mg/ kg was clearly better than 100 mg/kg. There was also a significant difference between the control group and the 300 mg/kg group. Conclusion: In the present study, AB plant extract increased serum levels of anti-inflammatory cytokines and decreased proinflammatory cytokines in the MS animal model.

Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

Background and aimsMinimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. Materials and methodsEighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. ResultsMHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. ConclusionMHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

Cytokine expression of IL-8 before and after root canal treatment in patients with symptomatic apical periodontitis: A clinical trial.

Thirty-six patients were allocated according to their pulp status into two experimental groups (n = 18) receiving the same treatment protocol; group 1: Vital pulps with SAP, and group 2: non-vital pulps with SAP. Conventional endodontic treatment was done on two visits; isolation and disinfection of the operative field were undertaken, and two-stage access cavity preparation was implemented. The first pre-instrumentation peri-apical sample (S1) was collected prior to cleaning and shaping procedures. A 2.5% NaOCl irrigation was used to thoroughly irrigate the canal after performing root canal preparation utilising the ProTaper Next (PTN) rotary system. After 1 week, the second post-instrumentation peri-apical sample (S2) was collected. Using an ELISA kit, the quantity of IL-8 was evaluated following the collection of all samples. In all pre-instrumentation samples, IL-8 was detected (100%). The level of IL-8 expression was significantly decreased from the S1 to S2 of all samples (p < 0.001). The intra-group comparison showed a statistically significant reduction in the level of IL-8 expression between S1 and S2 in both vital and non-vital groups where p < 0.001* in both groups. The inter-group comparison of levels of IL-8 expression (vital and non-vital) revealed a significant difference between both groups regarding the pretreatment sample with the higher levels of IL-8 shown in the non-vital group (p < 0.001). While in the post-treatment sample, both groups showed a significant reduction in the level of IL-8 expression but the difference between them was not statistically significant (p = 0.226). Root canal instrumentation seems to be efficient in decreasing the levels of anti-inflammatory cytokines, namely IL-8. Further research should clarify how intra-canal medicaments affect inflammatory mediator levels.

The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation.

Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo. The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo, oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic.

Hepatoprotective effects of Nigella Sativa oil against acrylamide-induced liver injury in rats

Acrylamide (AA) is a heat-induced carcinogen founds in some foods due to cooking or other thermal processes. This study was designed to investigate the possible protective efficacy of Nigella sativa essential oil against acrylamide-induced liver toxicity. Four groups of 32 male Wistar albino rats were formed. The control group was fed ad libitum. Acrylamide was administered to the rats in Group AA at a daily dose of 40 mg/kg by gavage. Nigella sativa essential oil was administered intraperitoneally at a dose of 10mg/kg to the rats in Group NS. In Group AA+NS, daily applications of acrylamide and Nigella sativa essential oil were applied simultaneously as mentioned above. The trial period lasted 15 days. While acrylamide statistically increased MDA levels in liver tissue (P&amp;lt;0.05), (146.13 %) and decreased GSH and SOD activity statistically (P&amp;lt;0.05), (55.28% and 40.46%). In addition, liver proinflammatory cytokine levels increased due to acrylamide administration (P&amp;lt;0.05), [TNF-α (78.17%), IL-6 (76.08%)], anti-inflammatory cytokine levels (P&amp;lt;0.05), [IL-10 (61.16%)] decreased. Co-administration of Nigella sativa essential oil with acrylamide significantly reduced oxidative stress and pro-inflammatory cytokine levels in liver tissues (P&amp;lt;0.05). In conclusion, our findings highlighted the potential therapeutic role of Nigella sativa essential oil in preventing acrylamide-induced hepatotoxicity.

Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice

WSMoL, a water-soluble lectin from the seeds of Moringa oleifera, present several biological activities. This work aimed to evaluated the toxicity and antitumor activity of WSMoL. To analyze toxicity, it was determined hematological, biochemical and histological parameters; consumption of water and feed as well as the weight of the animals. Antitumor analysis included evaluation of tumor weight, histology and cytokine levels. Acute toxicity assay revealed 60% mortality of animals treated with lectin at 200 mg/kg i. p. At 100 mg/kg i. p., the animals showed a decreased food and water consumption as well weight gain in comparison with control. However, no animal died and there were no alterations in blood parameters or histological analysis. Antitumor activity evaluated at safe doses (2.5, 5 and 10 mg/kg) showed a significant reduction in tumor weight. Tumor photomicrographs evidenced that WSMoL treatment reduced dissemination of tumor cells. WSMoL (5 and 10 mg/kg) significantly enhance the immune function in the tumor environment as showed by increased the levels of pro-inflammatory (TNF-α, IFN-γ, IL-2, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines. In conclusion, WSMoL showed in vivo antitumor activity in mice bearing sarcoma 180 tumor, probably by increase the immune response against the tumor.

Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages.

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.

The Effect of Moderate-Intensity Physical Exercise on Some Serum Inflammation Markers and the Immune System in Rats Fed Intermittent Fasting with a High-Fat Diet.

Background and Objectives: This study aimed to investigate the impact of moderate-intensity physical exercise on serum inflammation markers and the immune system in rats that were fed a high-fat diet (HFD) with intermittent fasting. Materials and Methods: A total of 48 Wistar albino male rats were included in the study and divided into eight groups, each consisting of six rats. Group 1 served as the control group (CG), receiving a standard diet. Group 2 followed the standard nutrition program with intermittent fasting (CG + IF). Group 3 underwent exercise with a standard diet (CG + E). Group 4 underwent both a standard diet with intermittent fasting and exercise (CG + IF + E). Group 5 was fed a high-fat diet (HFD). Group 6 received a high-fat diet with intermittent fasting (HFD + IF). Group 7 followed a high-fat diet with exercise (HFD + E). Group 8 underwent both a high-fat diet with intermittent fasting and exercise (HFD + IF + E). The study lasted for 8 weeks. Results: The results of the analysis show that lymphocyte cell levels in groups HFD + IF, HFD + IF, and HFD + IF + E were higher compared to groups CG-HFD (p < 0.05). Additionally, B lymphocyte and monocyte cell levels were higher in group HFD + IF + E compared to groups CG, CG + IF, and CG + IF + E, as well as CG, CG + IF, and CG + E, respectively. TNF-α levels were significantly higher in group HFD compared to the other groups. Furthermore, IL 10 levels were higher in group HFD + IF + E compared to the other groups. Conclusions: These findings indicate that moderate exercise and intermittent fasting, particularly in groups fed a high-fat diet, increased anti-inflammatory cytokine levels, and certain immune system cell counts, while decreasing pro-inflammatory cytokine levels.

Lactiplantibacillus plantarum 124 Modulates Sleep Deprivation-Associated Markers of Intestinal Barrier Dysfunction in Mice in Conjunction with the Regulation of Gut Microbiota.

Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.

The oral protective efficacy of magnolol against Aeromonas hydrophila and A. veronii infection via enhancing anti-inflammatory ability in goldfish (Carassius auratus).

Aeromonas hydrophila and A. veronii are widespread and important critical pathogenic bacteria in the aquaculture industry and cause severe economic damage. At present, magnolol has been proved to be a broad-spectrum antibacterial activity, such as A. hydrophila, Staphylococcus aureus and Streptococcus mutans. In order to explore the cause of in vivo disease resistance of magnolol and promote its safe application in aquaculture, the pathological detection and changes in immune indicators of fish after feeding with magnolol were conducted in this paper. Results showed that the diets supplemented with magnolol (3 g magnolol/kg commercial feed) significantly increase the expression level of anti-inflammatory cytokines (IL-10, TGF-β and IL-4) in the liver of goldfish (p < .05). Additionally, the expression levels of proinflammatory cytokines (IL-1β, IL-8 and IFN-γ) did not increase significantly. Subsequently, this study investigated the resistance of goldfish to A. hydrophila and A. veronii infection after feeding with magnolol. The results showed that the survival rates of treatment groups fed 3 g magnolol/kg commercial feed daily increased by 23.1% and 38.5% after 10 days post A. hydrophila and A. veronii (p = .0351) infection, respectively. Meanwhile, growth performance (body weight and length), major internal organs (liver, spleen, kidney and intestine) and the serum biochemistry indicators (ATL and AST) all exhibited no significant adverse effects after the goldfish fed with magnolol for 30 days. TP showed an increasing concentration in the treatment group (p < .05). Results of the mRNA expression of stress response indicated that the expression level of cyp1a and hsp70 was significantly down-regulated after a 30-day treatment (p < .05), and the two genes recovered to the similar level as the control group after a commercial feed diet. In brief, the diets supplemented with magnolol protected the host from the excessive immune response caused by A. hydrophila and A. veronii via enhancing its anti-inflammatory capacity and had no adverse effects with feeding.

Characterization of Leukocyte- and Platelet-Rich Plasma Derived from Female Collage Athletes: A Cross-Sectional Cohort Study Focusing on Growth Factor, Inflammatory Cytokines, and Anti-Inflammatory Cytokine Levels.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as "must-check" parameters to characterize individual PRP preparations prior to clinical trials.

Naringenin suppresses aluminum-induced experimental hepato-nephrotoxicity in mice through modulation of oxidative stress and inflammation.

Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.

Bsep/Abcb11 knockout ameliorates Schistosoma mansoni liver pathology by reducing parasite fecundity.

Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract S. mansoni-induced inflammation and fibrosis. Adult FVB/N wild type (WT) and Abcb11/Bsep-/- mice were infected with either 25 or 50 S. mansoni cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of proinflammatory cytokines and fibrotic markers, hepatic hydroxyproline content and FACS analysis were performed. Bsep-/- mice infected with S. mansoni showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in infected Bsep-/- mice, inflammatory cells such as M2 macrophages and Mac-2/galectin-3+ cells were reduced in these animals. Accordingly, mRNA-expression levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased in Bsep-/- mice upon infection. Furthermore, infected Bsep-/- mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. This outcome could arise from elevated serum BA levels and lower blood pH in Bsep-/- mice. The loss of Bsep and the resulting changes in bile acid composition and blood pH are associated with the reduction of parasite fecundity, thus attenuating the development of S. mansoni-induced hepatic inflammation and fibrosis.

Morphofunctional Changes in Brain and Peripheral Blood in Adult and Aged Wistar Rats with AlCl3-Induced Neurodegeneration.

the general lifespan has been prolonged greatly during the past century, and the incidence of age-associated diseases, including neurodegenerative ones, has increased as well. However, modelling of age-related pathologies is mostly conducted on adult rodents. We studied morphofunctional changes in the brain and peripheral blood of adult Wistar rats in comparison with old Wistar rats to determine age-related physiological changes and differences in adaptive reactions to AlCl3 exposure. the work was performed on adult and old male Wistar rats. The animals consumed a 100 mg/kg solution of AlCl3 each day for 60 days. Morphological changes of neurons and microglia, mRNA expression levels of pro-inflammatory and anti-inflammatory cytokines, microglia activation markers, amyloid-related proteins, and hallmarks of cellular senescence, monocyte, and lymphocyte subpopulations in the peripheral blood were examined. old rats showed increasing hyperchromic neurons in the hippocampus; activation of microglia; upregulation of pro-inflammatory cytokines and cellular senescence markers; downregulation of anti-inflammatory cytokines; and Hif-1a and a decrease in B-cells and monocyte in peripheral blood. compared to young animals, aged rats respond to aluminum exposure with a severe decline of most cells' function and irreversible neuronal loss. Regarding all reported data, neurodegeneration modelling and investigating of factors capable of accelerating or preventing it should be performed in experimental work on aged animals.

Effects of Different Ozone Doses Added to the Antibiotic Treatment on Cytokine Levels in Experimental Sepsis Model

We aimed to examine the changes caused by ozone therapy added to the antibiotic treatment on proinflammatory and anti-inflammatory cytokine levels in an experimental sepsis model formed with E. coli endotoxin. Rats were divided into 6 groups of 10 rats. Sepsis was formed by dosing 5 groups of rats with intraperitoneal E. coli endotoxin injection. For the first 3 groups, 0.6 mg/kg, 0.9 mg/kg, and 1.1 mg/kg doses of ozone therapy were added to the antibiotic treatment and group-4 only received antibiotic treatment. Group-5 was not treated. Group-6 received intraperitoneal serum physiologic injection simultaneously with the other groups. All treatments were sustained for 5 days. IL-1, IL-10, and TNF-alpha levels were detected in blood serum taken from rats sacrificed on day 6. It was seen that IL-1, TNF-alpha levels are significantly lower than the levels in other groups that received ozone therapy. In the comparisons amongst the groups receiving ozone therapy, it was observed that IL-1 levels do not have a significant difference and TNF-alpha levels are significantly lower in the two groups receiving lower doses than the group receiving a higher dose. There were no significant differences detected between groups at serum levels of IL-10 which is an anti-inflammatory cytokine. It was concluded that ozone added to the antibiotic treatment in sepsis could have a positive effect on survival rates by suppressing inflammatory process.