Liver Injury In Rats Research Articles

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

ObjectiveBased on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored. MethodsModels of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by 1H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR. ResultsPharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS. ConclusionFor the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Low-Dose Hexavalent Chromium Exposure Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Liver.

This study investigated the toxic effects of low-dose hexavalent chromium (Cr(VI)) on rat liver. Male specific pathogen-free (SPF) Sprague-Dawley (SD) rats (4-5weeks of age) were randomly divided into groups: saline, 0.05mg/kg Cr(VI), and 0.25mg/kg Cr(VI). The rats were subjected to intratracheal instillation of K2Cr2O7 suspensions or saline once weekly, for a total of five times. The results showed that the accumulation of Cr(VI) in the blood of the 0.25mg/kg K2Cr2O7 group was significantly higher than that in the saline group. Transmission electron microscopy (TEM) showed that exposure to hexavalent chromium caused endoplasmic reticulum (ER) oedema and a disordered arrangement. The levels of endoplasmic reticulum stress (ERS)-related proteins (ATF6, P-PERK, P-IRE1, Grp78, and CHOP) in the 0.25mg/kg K2Cr2O7 group were significantly higher than those in the saline group. The expression of apoptosis-inhibitory protein Bcl-2 was significantly lower in the 0.25mg/kg K2Cr2O7 group than that in the saline group, and the expression of apoptosis protein Bax was significantly higher in the 0.25mg/kg K2Cr2O7 group than that in the saline group, indicating that Cr(VI) increased apoptosis. These findings revealed that Cr(VI) may be involved in rat liver injury by initiating ERS-mediated apoptosis. The expression of ATF6, P-PERK, P-IRE1, and Bax in the 0.05mg/kg K2Cr2O7 group was not significantly different from that in the saline group, and the different effects produced by the two different dose groups provide a possible experimental basis for further study of occupational exposure limits.

The Role of BNIP3 and Blocked Autophagy Flux in Arsenic-Induced Oxidative Stress-Induced Liver Injury in Rats.

Arsenic is a widely distributed environmental toxic substance in nature. Chronic arsenic exposure can cause permanent damage to the liver, resulting in the death of poisoned patients. However, the mechanism of liver damage caused by arsenic poisoning is yet unclear. Here, four different concentrations of sodium arsenite (NaAsO2) (0mg/L (control group), 25mg/L, 50mg/L, and 100mg/L group)were established to induce liver injury in rats. Taking this into account, the relationship and potential mechanisms of oxidative stress, Bcl-2/adenovirus E1B-19-kDa-interacting protein 3 (BNIP3), and inhibition of autophagy flux in liver injury caused by arsenic poisoning were studied. The results indicated that long-term exposure to NaAsO2 could induce oxidative stress, leading to high expression of BNIP3, thereby impaired autophagy flux, and ultimately resulting in liver damage. This research provides an important basis for future research on liver damage caused by chronic arsenic exposure and prevention and treatment with BNIP3 as the target.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury.Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats

Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats. Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology. C max, t max, and AUC 0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t 1/2, AUC 0−t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology. In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.

Functional Assessment of MGO Nanoparticle Supplementation in an Acute Liver Injury Rat Model

Magnesium supplements have been effective for modulating process of bile resistance, decrease oxidative stress and systemic inflammation. Current study was designed to functionally evaluate the MgO nanoparticle supplementation in an acute liver injury rat model. The animals were randomly divided into five groups. All groups were administrated with CCl4 to induce hepatic injury except of negative control group which received only vehicle. CCl4 administration is followed by MgO nanoparticles in the concentration of 150 and 300 mg/kg in low dose and high dose treated group respectively except of standard control group. After 21 days of treatment, the animals were sacrificed to collect blood and liver samples. Serum levels of bilirubin, AST, ALT and ALP were determined. Liver sample was also subjected to RNA isolation by Trizol method followed by the cDNA synthesis and Real Time PCR. In addition, lipid profile was also assessed. The data obtained was analyzed by one way analysis of variance (ANOVA). The results showed that levels of bilirubin, AST, ALT and ALP were significantly elevated in positive control group while MgO treated groups, somehow, had normal ranges of these enzymes. Furthermore, the qPCR results showed that the expression of Farnesoid X receptor (FXR), transcriptional regulator of the bile salt export pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP), is reduced in positive control group, while nanoparticles treated groups had normal expression of these genes. In conclusion, our data showed that MgO nanoparticles possess hepatoprotective activity against hepatic injury.

Correlation between drug-induced liver injury in rats caused by Xianling Gubao oral preparation and extraction process

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P&lt;0.05), a significant decrease in liver-to-brain ratio(P&lt;0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P&lt;0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P&lt;0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.

Metabolomics study of the hepatoprotective effects and mechanism of aqueous extract of Dendrobium nobile Lindl. on alcohol liver injury in rats.

Dendrobium nobile Lindl. (DNL) is effective for the treatment of alcohol liver disease (ALD), but the underly mechanism is still unclear. This research aimed to investigate the effects and mechanism of aqueous extract of Dendrobium nobile Lindl (AEDNL) in ALD rats based on a metabolomics approach. In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis. Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism. The research could provide novel evidence of the protective effects of AEDNL on ALD.

Mesenchymal stem cell therapy modulates macrophage dynamics in ARDS-associated liver injury in rats

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening pulmonary condition characterized by severe hypoxemia and respiratory failure. Beyond its devastating impact on the lungs, ARDS often triggers systemic responses affecting vital organs throughout the body. One such organ commonly affected is the liver, which experiences various degrees of injury during the course of ARDS. Pathophysiological changes in liver during ARDS, particularly polarization of Kupffer cells during the disease and its treatment, have drawn increasing attention. Purpose. To explore the macrophage transformation in liver injury associated with ARDS and investigate the potential of mesenchymal stem cell (MSC) therapy as a means to modulate macrophage responses and mitigate liver injury. Materials and methods. 72 mature male Wistar rats were randomly allocated to nine experimental groups as follows: the control group, groups assessed at 3 days, 7 days, and 28 days following intranasal LPS administration, groups that received 24 hours of LPS followed by 2 days of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), groups exposed to 4 days of LPS and 3 days of hUC-MSCs, groups subjected to 14 days of LPS and 14 days of hUC-MSCs, groups treated with LPS 21 days and 7 days with hUC-MSCs injection, and a control group assessed 3 days after hUC-MSCs injection. For the administration of hUC-MSCs, intraperitoneal injections were performed at a dose of 1∙106 cells/kg body weight. Immunohistochemistry was employed to analyze macrophage subpopulations in liver tissues. Animal experiments adhered to ethical guidelines. Results. Early ARDS stages showed increased M1 macrophages, indicating pro-inflammatory responses, while later stages showed M2 macrophage activation, suggestive of anti-inflammatory and tissue repair roles. MSC administration facilitated the transition from M1 to M2 macrophages, promoting an anti-inflammatory milieu. Conclusions. MSCs demonstrate the potential to modulate macrophage polarization into M2 anti-inflammatory phenotype. Such findings reflect one of the mechanisms of MSC action which holds practical significance for future ARDS therapies, aiming to mitigate excessive inflammation and enhance tissue repair.

Comparative study between the effect of mesenchymal stem cells microvesicles versus ozone on induced liver injury in adult male albino rats (Histological & Immunohistochemical study)

Liver disease accounts for approximately 2 million deaths er year worldwide. Liver fibrisis results from chronic injury to the liver. If not effectively treated in time, liver fibrosis may transform into liver cirrhosis. MVs are recognized as potential biomarkers and important theraputic tools for a wide sectrum of diseases. Medical ozone has the ability to protect the body against pathological conditions caused by oxidative stress. The influence of ozone and MVs on CCL4 induced liver fibrosis was investigated in this study. Forty-eight adult male albino rats were divided into four equal groups. I control, II CCL4 group, III ozone and IV microvesicles groups. Liver fibrosis was induced in group II, III & IV using 12 SC injections (0.5 ml/kg body weight) of CCL4 dissolved in olive oil twice ber week for weeks. Blood samples were obtained to estimate serum ALT & AST. Liver tissues were processed for measurment of GSH & SOD, light and electron microscopic examination. H&E staine sections og group II showed dilated congested sinusoids and centralveins, mononuclear infiltrations, vacuolations and dark nuclei. Ultrastructurally, group II revealed irregular heterochromatic nuclei of hepatocytes, small scanty mitochondria & vacuolations. Morphometric & statistical analyses were performed. Group III showed some improvement, however, group IV showed more imrovement. The results indicates that MVs caused marked improvement than ozone against CCL4 induced liver damage via antioxidant & antiinflammatory properties.

Potential mechanisms underlying the effect of hepatocyte growth factor on liver injury in short bowel syndrome model rats.

The purpose of this study was to investigate the autophagy associated with apoptosis in hepatic damage in the short bowel syndrome rat model. SD rats underwent jugular vein catheterization for continuous total parenteral nutrition (TPN) and 90% small bowel resection. Animals were divided into two groups: TPN plus SBS (Control group) or TPN plus SBS plus intravenous administration of HGF (HGF group). On day 7, the rats were harvested, and hepatocellular injury was evaluated. In an SBS rat model, hepatic steatosis and lobular inflammation were histologically suppressed in the HGF group (p < 0.01). The expression of tumor necrosis factor-α in the HGF group tend to be higher than that in the control group (p = 0.13). The gene expression of transforming Growth Factor-β in the HGF group was suppressed compared to the control group (p < 0.01). HGF treatment may have an antiapoptotic effect via the intrinsic pathway by caspase 9. Protein expressions of Rubicon (p = 0.03) and p62 (p < 0.01) in the HGF group were found to have increased compared to those in the control group. The inhibitory effect of HGF on hepatic steatosis remains unclear, and further studies focusing on the mechanisms of fat accumulation are needed.

Utilizing epoxy Bletilla striata polysaccharide collagen sponge for hemostatic care and wound healing

Hemostatic materials that are lightweight and possess good blood absorption performance have been widely considered for use in modern wound care. Natural hemostatic ingredients derived from traditional Chinese medicine have also received extensive attention. Bletilla polysaccharides are valued by researchers for their excellent hemostatic performance and good reactivity. Collagen is favored by researchers due to its high biocompatibility and low immunogenicity. In this study, Bletilla striata polysaccharide, the main hemostatic component of Bletilla striata, was activated by epoxy groups, and epoxidized Bletilla striata polysaccharide (EBSP) was prepared. Then, EBSP was crosslinked with collagen under alkaline conditions, and a new hemostatic material that was an epoxidized Bletilla polysaccharide crosslinked collagen hemostatic sponge was prepared. We demonstrated that endowing collagen with better hemostatic performance, cytocompatibility, and blood compatibility does not destroy its original three-stranded helical structure. Compared with the medical gauze, hemostasis time was shorter (26.75 ± 2.38 s), and blood loss was lower (0.088 ± 0.051 g) in the rat liver injury hemostasis model. In the rat model of severed tail hemostasis, hemostasis time was also shorter (47.33 ± 2.05 s), and the amount of blood loss was lower (0.330 ± 0.122 g). The sponge possessed good hemostatic and healing performance.

Antioxidative and Anti-Inflammatory Protective Effects of Fucoxanthin against Paracetamol-Induced Hepatotoxicity in Rats.

Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-α, IL-1, IL-6, NF-kB, INF-γ, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings.

Protective effect of Moringa oleifera Crude Leaf Extract on Chlorpyrifos-induced Liver damage in Wistar Albino Rats

Chlorpyrifos is a broad spectrum insecticide that is most frequently used in food production in the European Union (EU) until 2020. This compound exhibits a wide range of biological activity. It is applied in most agricultural products and households to combat pests. Chlorpyrifos acts by inhibiting cholinesterase activity that can lead to the alteration of normal biochemical and physiological conditions of the body. This study is aimed at investigating the effect of Crude Leaf extract of Moringa oleifera on Chlorpyrifos induced Liver injury in Wistar Albino Rats. Sixteen (16) Wistar Albino Rats weighing between 100g-250g were divided into four (4) Groups (Grp) of four (4) Rats each. Grp I serves as Normal Control (feed and water ad libitum), Grp II Negative Control (10mg/kg Chlorpyrifos mixed feed), Grp III serves as Extract grp (10mg/kg Moringa oleifera mixed feed) and Grp IV serves as Treatment grp ((10mg/kg Chlorpyrifos + 10mg/kg Moringa oleifera) mixed feed). The feeds were administered in pellets. The experiment lasted for twenty eight (28) days, after which serum was obtained for biochemical parameter (Liver function). Grp II shows an increased liver marker enzymes AST (173.75±21.84μ/L) when compared to Grp I with value of (146.60±21.94μ/L) and Grp III with a value of (140.75±11.12μ/L) and ALT (40.00±5.83 μ/L) compared to grp I and grp III with values of (33.80±4.49μ/L) and (33.25±7.41μ/L) respectively. ALP (Grp II) with a value of (155.00±16.23μ/L) compared to Grp I and Grp III (69.00±24.71μ/L) and (52.00±17.06μ/L) respectively. ALB (30.50±2.08g/L) when compared to Grp I and Grp III shows values of (28.60±2.41g/L) and (29.50±0.58g/L) respectively. There was no significant difference at P˃0.05. However, ALP shows a significantly higher value at P˂0.001. Values for all Liver enzymes were lower with P˃0.05 in Grp IV when compared with Grp II. There is also a reduced feed intake in Grp II at different days with P˃0.05 when compared with Grps III and IV. The Extract was found to have improved the hepatic disorder that was induced by Chlorpyrifos. The result showed some level of hepato-protective activities of Moringa oleifera Crude Leaf extract in Rats exposed to Chlorpyriphos.

Hippocratea africana Root Extract and Fractions Ameliorates Paracetamol (PCM)-Induced Oxidative Stress and Liver Injuries in Rats

Aim: The antidotal potential of Hippocratea africana root, which is used locally to cure poisoning, was studied in rats.&#x0D; Methodology: The hepatoprotective activity of the root extract (200-600 mg/kg), fractions (dichloromethane (DCM) and aqueous, 400 mg/kg) and Silymarin (100 mg/kg), were investigated against paracetamol-induced liver injury in rats. Assay of liver function parameters, markers of antioxidative stress in addition to liver histological analysis were employed to evaluate the hepatoprotective potential of root extract and fractions.&#x0D; Results: Administration of the root extract (200-600 mg/kg) caused significant (P &lt; .05-.001) increases in the blood levels of total protein and decreases in direct and total bilirubin, and the liver biomarker enzymes ALT, AST, and ALP caused by paracetamol administration. Most of the time, the effects were dose-dependent. When compared to the negative control group of animals (organotoxic-treated animals), the histology of the liver sections from animals treated with extract, fractions, and silymarin revealed a decrease in pathological characteristics. These histological observations suggest significant hepatoprotective potentials which were in line with the chemical pathological alterations.&#x0D; Conclusion: The outcome of the study indicated that root extract and fractions of Hippocratea africana have antioxidative stress potentials and hepatoprotective action against harmful substances, maybe as a result of its phytochemical constituents' activity.

Chitosan based Janus cryogel with anisotropic wettability, antibacterial activity, and rapid shape memory for effective hemostasis

Excessive bleeding and bacterial infection leading to death is a major concern worldwide, particularly in cases of deep and narrow noncompressible hemorrhage. Herein, a novel Janus cryogel with anisotropic surface wettability, antibacterial activity, and rapid shape recovery was designed by constructing a hydrophilic porous cryogel using chitosan (CS), acacia gum (AG), and quaternized mesoporous bioglass (QMBG), with subsequent surface hydrophobic modification using octadecanol. The asymmetric hydrophobic surface modification of octadecanal endowed OCAQ with outstanding antiblood and antibacterial permeability, effectively preventing blood outflow and the invasion of bacteria to the wound. The hydrophilic parts with interconnected macroporous structure give the cryogel with ultra-high water uptake (5167 ± 182 %) and rapid water-trigged shape recover ability (≈2.1 s). The presence of active CS, AG, and QMBG in cryogel contributes to its exceptional blood clotting ability. Janus cryogel presents outstanding hemostatic performance (0.14 ± 0.03 g) in rat's liver injury model. Moreover, Janus cryogel exhibits excellent antibacterial properties due to the combination of its hydrophobic surface and antimicrobial quaternary amine groups. Meanwhile, the Janus cryogel has favorable hemocompatibility and biocompatibility. A Therefore, the Janus cryogel will become a candidate with great potential for clinical application of noncompressible wound as a multifunctional dressing.

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1β (IL-1β) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

Hepatoprotective study of Indonesian water kefir against CCl4-induced liver injury in rats

Context: Water kefir is a fermented beverage that is typically made in the home by inoculating a sugar-rich solution with a microbial community (water kefir grains). Several studies on the metabolite content and hepatoprotective effects of water kefir have been published, but carbon tetrachloride (CCl4)-induced acute liver injury has not been studied. Aims: To evaluate the efficacy of water kefir in vivo against hepatoprotective CCl4-induced acute liver injury and to in silico investigate metabolites that play an important role in hepatoprotective mechanisms. Methods: The present study aimed to investigate the hepatoprotective activity of water kefir in an animal model caused by CCl4. Furthermore, using molecular docking, the metabolites found in water kefir were evaluated for their role in the NF-κB and Nrf2 signaling pathways. Results: Water kefir significantly and dose-dependently alleviated acute liver injury caused by CCl4. Water kefir administration at all doses produced results comparable to the positive control (Curcuma extract). Molecular docking simulations showed that, compared to Nrf2, the 25 metabolites were more likely to interact with the NF-B receptor. Fumaric acid is the strong metabolite that interacts with the NF-κB receptor with a free energy of binding and an inhibition constant of -6.66 kcal/mol and 13.22 µM, respectively. Conclusions: Water kefir administration improved the condition of liver damage, characterized by a decrease in serum levels of AST, ALT, TNF-, TGF-, and an improvement in the liver tissue profile. In silico evaluation showed that the metabolites in water kefir were able to interact with target proteins in the NF-B and Nrf2 pathways. It was concluded that water kefir improves the condition of the liver by reducing the level of necrosis and fibrosis.

Mechanism of the Effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid in Treating Alcoholic Rat Liver Injury by Metabolomics.

Compound Anoectochilus roxburghii (Wall.) Lindl oral liquid (CAROL) is often as a hepatoprotective agent. The present study aimed to elucidate the protective mechanism of CAROL against alcoholic liver injury in rats by untargeted metabolomics combined with multivariate statistical analysis. An alcoholic liver disease model was established in sprague-dawley (SD) rats by gavage of alcohol, and CAROL treatment was administered. The hepatoprotective effect of CAROL was evaluated by examining liver tissues changes and detecting biochemical index activities and cytokines in serum and liver homogenates. The metabolites in serum samples were examined using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and multivariate statistical analysis to screen for differentially expressed metabolites and Kyoto Encyclopedia of Genes and Genomes (KEGG) to assess potential metabolic pathways. CAROL has the potential to downregulate inflammation levels and alleviate oxidative stress. The differential metabolites are mainly engaged in riboflavin metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis metabolism, phenylalanine metabolism, pyrimidine metabolism, and vitamin B6 metabolism to achieve hepatoprotective effects. CAROL may exhibit beneficial hepatoprotective effects by reducing inflammation, mitigating oxidative stress, and modulating metabolites and their metabolic pathways.This study has important implications for advancing the clinical application of CAROL.

Empagliflozin Mitigates Ischemia/Reperfusion-induced Liver Injury in Rats: Modulation of NF-κB, SMAD-4, VEGF, and Fibrinogen Protein Expressions

Empagliflozin Mitigates Ischemia/Reperfusion-induced Liver Injury in Rats: Modulation of NF-κB, SMAD-4, VEGF, and Fibrinogen Protein Expressions