Liver Injury In Rats Research Articles

Hepatoprotective effects of ethanolic extract of Corallocarpus epigaeus roots on nitrobenzene-induced liver injury in Wistar rats

ABSTRACT This study examined the potential of Corallocarpus epigaeus ethanolic root extract to combat free radicals using DPPH, FRAP, hydroxyl radical, hydrogen peroxide, and nitric oxide scavenging assays. Rats were initially exposed to a single oral dose of nitrobenzene (50 mg kg−1 body weight), followed by a 15-d oral regimen of the ethanolic root extract of C. epigaeus at 200 mg kg−1 body weight. The assessment of serum liver marker enzymes (AST, ALT, and ALP), lipid peroxidation levels, antioxidant enzyme activities, and histopathological examinations of liver tissues were carried out. The C. epigaeus ethanolic root extract demonstrated antioxidant properties and contained flavonoids, tannins, carotenoids, lycopene, and phenolic compounds. In Nitrobenzene-induced rats, elevated serum markers and increased liver lipid peroxidation were observed that were normalized by the extract. It also increased antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Histopathological analysis confirmed the hepatoprotective effects of the extract.

Comparison of gauze packing, sponge-based, and hemostatic Surgicel wound stasis dressings to treat hemorrhages from grade IV liver injuries: An experimental study

BackgroundUncontrolled bleeding is still the major factor leading to preventable deaths following trauma. This study sought to assess the effectiveness of mini sponge-based wound stasis, cellulose-based local hemostatic, and traditional gauze dressings for the control of hemorrhages resulting from grade 4 liver injuries in rats. MethodsThirty Sprague-Dawley rats were divided into three equal groups. In the first group, a liver laceration was treated with gauze packing. The second group received XStat minisponge dressing (MDS), and the third group was administered a combination of MDS dressing and Surgicel hemostatic agent. After gaining access to the intra-abdominal cavity, a liver laceration measuring 10 mm in length, 5 mm in depth, and extending to the middle lobe was created. The dressings were removed after 2 and 10 minutes to assess the amount of bleeding, and any bleeding was documented again after 48 hours. Intraperitoneal adhesions were evaluated during euthanasia. ResultsAt 2 minutes post-injury, the gauze packing group had an average bleeding volume of 0.97±0.15 mL, compared to 1.08±0.25 mL in the MDS group (P=0.26) and 1.02±0.18 mL in the MDS+Surgicel group (P=0.69). At 10 minutes, the bleeding volumes were 0.13±0.05 mL, 0.22±0.01 mL (P=0.09), and 0.14±0.05 mL (P=0.19), respectively. At 48 hours, significant differences were observed in bleeding volumes (gauze: 0.55±0.18 mL, MDS: 1.15±0.21 mL, MDS+Surgicel: 0.82±0.06 mL, P<0.001). Mortality rates after 14 days were 0% in the gauze packing group, 60% in the MDS group (P=0.001), and 60% in the MDS+Surgicel group (P=0.001). The gauze packing group displayed no adhesions, while the other groups exhibited adhesions in the liver, bowel, omentum, and abdominal wall. ConclusionOur results indicate that, when it comes to managing bleeding in severe liver injuries, traditional gauze packing remains the tried-and-true method, showing superior effectiveness in terms of blood loss and mortality when compared to XStat minisponge dressings and the fibrillar Surgicel hemostatic agents.

Ginkgetin alleviates polystyrene microplastics-instigated liver injury in rats through Nrf-2/Keap-1 pathway activation

Polystyrene microplastics (PS-MPs) are potential toxicants that are reported to instigate oxidative stress (OS) in the liver. Ginkgetin (GK) is a natural biflavonoid with potential therapeutic activities. This experiment was executed to access the putative effect of GK against PS-MPs provoked hepatotoxicity. Four groups were formed from 48 rats including control, PS-MPs (0.01 mg/kg), PS-MPs (0.01 mg/kg) + GK (25 mg/kg) and GK (25 mg/kg) alone. The inebriation of PS-MPs markedly decreased the expressions of antioxidant genes and Nrf-2, besides escalating Keap-1 expression. It also decreased antioxidants i.e., glutathione (GSH), glutathione S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione reductase (GSR) activities, while remarkably upsurged reactive oxygen species (ROS) along with malondialdehyde (MDA) contents. Additionally, a notable escalation in hepatic serum markers i.e., alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate aminotransferase (AST) level was observed. Furthermore, PS-MPs exposure escalated inflammatory biomarkers, tumor necrosis factor-α (TNF-α), interleukin- 6 (IL-6), nuclear factor-kappa B (NF-kB), interleukin-β (IL-1β) level and cyclooxygenase-2 (COX-2) activity as well as augmented Caspase-3 along with Bax expression and decreased Bcl-2 expression. Nevertheless, GK treatment notably abated PS-MPs prompted liver injuries owing to its hepatoprotective efficacy.

Hepatoprotective effects of the xanthine oxidase inhibitor Febuxostat against thioacetamide-induced liver injury in rats: The role of the Nrf2/ HO-1 and TLR4/ NF-κB pathways

Experimental models of liver injury have been established utilizing thioacetamide (TAA), a classic liver toxic chemical that causes organ damage via oxidative stress and inflammatory induction. This study examined the impact of Febuxostat (a xanthine oxidase inhibitor; Febu, 10–15 mg/kg, orally) against TAA (500 mg/kg, i.p.) -induced liver injury in rats.Febu significantly attenuated TAA-induced alterations in liver function parameters, in addition to promoting hepatic antioxidant effects through a significant elevation of Heme-oxygenase-1(HO-1), nuclear factor erythroid 2-related factor2 (Nrf2), reduced glutathione (GSH) and superoxide dismutase (SOD) levels and reduction in hepatic malondialdehyde (MDA) content. Moreover, Febu improved the hepatic anti-inflammatory status by increasing the anti-inflammatory cytokine Interleukin (IL-10) level and reducing the levels of the pro-inflammatory cytokines (Nuclear factor kappa B (NF-κB), IL-1β, high-mobility group box1 (HMGB1), receptor for advanced glycation end products (RAGE), and toll-like receptor4 (TLR4) levels, in addition to suppressing the increased protein and mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-6, hepatic expression of TNF-α and activated mitogen-activated protein kinases (p-JNK/p-p38 MAPK). Histopathologically, Febu markedly normalized TAA-induced alteration in liver sections. In conclusion, Febu, in a dose-dependent fashion, refines TAA-induced hepatotoxicity by enhancing antioxidant capabilities and decreasing inflammatory signals.

Toxicokinetics and Tissue Distribution of the Hepatotoxic Triterpenoid Saponin Pterocephin A in Rats Using the Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) Method

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri, a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 (v/v) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0–2 min 30% B; 2–4 min: 30–80% B; 4–5 min: 80–98% B; 5–6.5 min: 98% B; 6.5–7 min: 98–30% B; and 7–8 min: 30% B, v/v) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02–15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver &gt; lung &gt; kidney &gt; intestine &gt; spleen &gt; testes &gt; heart &gt; stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity.

Antioxidant and hepatoprotective effects of methanolic seed extract of Telfairia occidentalis on carbon tetrachloride induced hepatic damage in wistar rats

BackgroundTelfairia occidentalis, a drought-resistant vegetable in West Africa, was studied for its hepatoprotective and therapeutic effects on carbon tetrachloride-induced liver injury in wistar rats. Earlier, the study found that the methanolic seed extract of T. occidentalis contained various phytochemicals, including tannins, flavonoids, terpenoids, alkaloids, phenols, cardiac glycosides, and steroids.MethodologyRats were treated with Telfairia occidentalis methanolic seed extract after being exposed to carbon tetrachloride for a duration of 14 days. Thirty (30) male and female Albino Wistar rats were used, and were divided into six (6) groups of five (5) animals apiece. The groups were as follows: Pre-treatment group (TOSE + CCl4 Group): this group received normal diet, water, and seed extract 400 mg/kg in 0.5 mL of olive oil for 13 days, then carbon tetrachloride 2 mL/kg in olive oil on the 14th day; Curative group (CCl4 + TOSE): this group received carbon tetrachloride 2 mL/kg administered on day 1 then seed extract for the remaining 13 days; and Concurrent Group (2CCL4 + TOSE); carbon tetrachloride 2 mL/kg given twice a week for 14 days (2 weeks) and seed extract daily.ResultsThe results of the study showed that, in comparison to the normal control group's AST (89.52 ± 4.91), ALT (33.60 ± 2.32), and ALP (31.03 ± 0.97), the group that received CCl4 alone had significantly higher serum levels of these indices AST (122.43 ± 3.89), ALT (85.80 ± 3.22), and ALP (42.78 ± 1.83) as well as liver tissue necrosis. Telfairia occidentalis seed extract treatment prevented liver damage and restored liver architecture, as evidenced by significantly lower values of ALT, ALP, and AST (84.73 ± 6.28#, ALT (52.40 ± 1.63), ALP (25.52 ± 1.60), and ALT (71.40 ± 1.69, ALP (27.68 ± 1.95#)) following or before CCl4 administration. Furthermore, the data showed that GPx, SOD, and CAT activities were significantly (P < 0.05) lower in the rats given CCl4 than in the control group. The extract alone considerably raised the antioxidant levels in comparison to the control.ConclusionThe study found that the treatment with Telfairia occidentalis seed extract significantly increased the activities of glutathione peroxidase and SOD in rats, and also reduced levels of AST, ALT, and ALP. Authenticating the therapeutic benefits of Telfairia occidentalis seed extract.

A chitosan macroporous hydrogel integrating enrichment, adsorption and delivery of blood clotting components for rapid hemostasis

Traditional hemostatic hydrogels face considerable limitations in achieving rapid control of severe bleedings, a crucial factor in reducing casualties in both military and civilian settings. This study presents a chitosan-based hemostatic hydrogel with interconnected secondary macropores designed to enhance interactions with blood clotting components by reducing diffusion resistance and increasing contact area. The macropores were created using a straightforward process involving NaOH-mediated SiO2 template dissolution and NH3 generation. The resulting macroporous structure increased the hydrogel's overall porosity without compromising its viscoelasticity. Functional studies demonstrated that the macroporous hydrogel effectively concentrated and adsorbed blood clotting components, while also facilitating the delivery of artificially embedded clotting factor to further expedite clot formation. These combined actions resulted in improve hemostatic efficacy, reducing whole blood clotting time by over 94 % in vitro. Furthermore, in vivo studies using rat tail amputation and liver injury models showed a reduction in blood loss by over 65 % and a decrease in bleeding time by over 70 %. Additionally, the porous chitosan hydrogel exhibited minimal biotoxicity and promoted biodegradability in vivo. In conclusion, this work introduces a macroporous chitosan-based hemostatic hydrogel with great potential for rapid hemorrhage control.

Efficacy of Eugenol Loaded Chitosan Nanoparticles on Sepsis Induced Liver Injury in Rats

Background: Sepsis is a life-threatening condition responsible for high morbidity and mortality rates around the world and is characterized by a dysregulated host response to infection, resulting in multiple organ dysfunctions. Eugenol is a phenolic aromatic compound derived from clove oil. It has anti-inflammatory, antioxidant, antibacterial, antiviral, antifungal, and anticancer characteristics, which have led to its extensive use in diverse fields, including cosmetology, medicine, and pharmacology. The ongoing study aimed to evaluate the efficacy of eugenol-loaded chitosan nanoparticles (EC-NPs) on sepsis-induced liver damage using the cecal ligation and puncture (CLP) model. Methods: Thirty male albino rats were randomly divided into five groups: Sham, sepsis, and septic rats treated with chitosan, eugenol, or EC-NPs. Results: EC-NPs showed excellent antibacterial, antioxidant, and anti-inflammatory effects in vitro. EC-NP administration significantly improved liver function, as indicated by the decreased liver enzyme activities and C-reactive protein (CRP) level, as well as the increase of albumin content. Moreover, EC-NPs caused an increase in glutathione-reduced and antioxidant enzyme activities, as well as a reduction of malondialdehyde and nitric oxide formation. In addition, the EC-NP treatment reduced the DNA damage in septic rats; also, the EC-NP treatment repaired, to some extent, the abnormal architecture of the hepatic tissues of septic rats. Furthermore, the immunohistochemical examination showed a marked decrease in inflammation through the reduction of TNF-α and IL-1β expression. Conclusion: In conclusion, EC-NPs attenuated liver injury in sepsis through its antiinflammatory, anti-bacterial, and anti-oxidant activities and protection of DNA.

Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models

ObjectiveDisruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques. MethodsThree liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats. ResultsFMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways. ConclusionFMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.

LC-QTOF-MS/MS metabolic profiling and hepatoprotective effects of Litsea monopetala bark methanol extract against liver injury in rats and HepG2 cells.

Fresh stem bark decoction of Litsea monopetala has been practiced for the treatment of jaundice and other liver disorders by the tribal communities of Thakht-e-Sulaiman hills from West Pakistan. As per the folkloric claim, this study aims to identify the phytoconstituents and evaluate the hepatoprotective action of stem bark methanol extract of L. monopetala (LMME). The in-vitro hepatoprotective effect of L. monopetala was performed by H2O2-induced toxicity in the HepG2 cell line and in-vivo by cclt;sub>4-induced hepatotoxicity in Wistar albino rats taking Silymarin as standard drug. Phytoconstituents were identified using LC-QTOF-MS analysis followed by in-silico docking and validation. Molecular docking interactions between identified compounds of L. monopetala and two target proteins, namely 1VJY and 5HYK were presented. In this study, treatment with LMME at 100 µg/mL showed 67.73 % cell viability as compared to H2O2 (100 µM) treated alone i.e., 18.55 % in the HepG2 cell line. In-vivo treatment of LMME reversed the altered serum biochemical parameters and reduced the inflammatory response similar to that of the Silymarin-treated group supported by histopathological investigation. This research reveals that L. monopetala is a rich source of flavonoids and phenols which supports its hepatoprotective effects and is proposed for its usage as a promising hepatoprotective agent after controlled trials.

Evaluating the Root Extract of Reynoutria ciliinervis (Nakai) Moldenke: An Analysis of Active Constituents, Antioxidant Potential, and Investigation of Hepatoprotective Effects in Rats

Reynoutria ciliinervis (Nakai) Moldenke (R. ciliinervis) root, a traditional Chinese medicine, was found to exhibit remarkable pharmacological properties through a series of comprehensive investigations. Our study commenced with a qualitative phytochemical analysis that identified 12 bioactive compounds within the plant. Subsequently, utilizing ultraviolet-visible spectrophotometry, the methanol extract emerged as the optimal solvent extract, which was abundant in diverse classes of compounds such as carbohydrates, phenolics, steroids, alkaloids, phenolic acids, and tannins. In vitro antioxidant assays underscored the exceptional free radical scavenging, metal ion chelation, hydrogen peroxide scavenging, singlet oxygen quenching, and β-carotene bleaching capabilities of the methanol extract, significantly outperforming other solvent extracts. Further ultra high-performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry analysis revealed the presence of 45 compounds, predominantly anthraquinones and phenolics, in the methanol extract. The extract demonstrated robust stability under various conditions, including high temperatures, varying pH levels, and simulated gastrointestinal digestion as well as efficacy in inhibiting the oxidation in edible oils. Acute toxicity tests in mice confirmed the safety of the methanol extract and provided a valuable dosage reference for future studies. Importantly, high-dose methanol extract exhibited a significant pre-protective effect against D-galactosamine-induced liver injury in rats, as evidenced by reduced alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, malondialdehyde levels, and elevated catalase and albumin levels. These findings suggest a potential role for the methanol extract of R. ciliinervis root in treating oxidative stress-related disorders, highlighting the plant’s immense medicinal potential. Our research offers a thorough evaluation of the bioactive components, antioxidant properties, stability, and liver-protecting effects of the methanol extract, setting the stage for deeper investigation and potential clinical applications.

A traditional medicinal food &lt;i&gt;Arum rupicola&lt;/i&gt; (Kardeh) ameliorates thioacetamide-induced hepatotoxicity in animal model: Role of PCNA/Bax, oxidative stress, and inflammatory cytokines

Nutraceuticals are major contributors to human health because of their modulatory effects on various physiological and pathological processes. Arum rupicola (Kardeh) is a traditional medicinal food used for many gastrointestinal and enzymatic disorders. The present study evaluates the acute toxicity and hepatoprotective effects of methanolic extracts of Arum rupicola (MEAR) in rat with thioacetamide (TAA)-induced liver injury in rat. Thirty Sprague-Dawley rats were divided into five groups: Group A, normal control, and group B, TAA control groups were treated orally with 10% tween 20; group C reference rat received daily of 50 mg/kg silymarin drug; Groups D and E rat received daily doses of 250 mg/kg and 500 mg/kg MEAR, respectively. In addition, group B–E received three injections of 200 mg/kg TAA weekly for 60 days. The safety evaluation of MEAR revealed nontoxic effects at 2,000 and 5,000 mg/kg dosage in rat. TAA inoculation provoked significant hepatotoxic alterations indicated by increased hepatocyte proliferation, endothelial tissue injury, ambiguous nucleus, and elevated cytoplasmic vacuoles. TAA treatment initiated increased inflammatory response and necrosis process in different areas of hepatic tissues. Meanwhile, MEAR treatment showed significant prophylaxis against TAA-induced hepatotoxicity, supported by its suppressing actions on oxidative stress, and apoptotic and inflammatory mediators. MEAR treatment significantly down-regulated proliferating cell nuclear antigen (PCNA) in both liver and spleen parenchymal tissues, lowered pro-apoptotic Bcl-2-associated X (Bax) proteins, reduced inflammatory and redox mediators, lowered transforming growth factor-beta tissue expression and malondialdehyde content, while, increased antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). The outcomes provided significant hepatoprotective potential of MEAR mediated by its modulatory effects on several cellular pathways, making it a viable source of a potent pharmaceutical discovery.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats

Cyclophosphamide (CP) is an alkylating anticancer drug with broad clinical application that is highly effective in the treatment of cancer and non-malignant diseases. However, the main limiting effect of CP is multi-organ toxicity due to damage to normal tissues. The aim of this study is to compare the hepatoprotective potential of selenium (Se) and boron (B) in CP-induced liver injury in experimental rats. The rats were randomly divided into six equal groups: Control (saline), 200 mg/kg CP (administered once on the fourth day of the experiment), 1.5 mg/kg Se (administered once/time daily for 6 days), 20 mg/kg B (administered once/time daily for 6 days), Se + CP and B + CP administered intraperitoneally (i.p.). Administration of CP leads to an increase in the levels of apoptotic markers (Bax, caspase-3), the apoptotic signaling pathway (Nrf2), oxidative stress indicators (TOS, OSI), lipid peroxidation markers (MPO, MDA), inflammation levels (NF-kB, TNF-α, IL-1β, IL -6), liver function markers (ALT, AST, ALP), while apoptosis markers (Bcl-2), apoptosis pathway (Keap-1), oxidative stress indicator (TAS), inflammation (IL -10) and intracellular antioxidant defense system (SOD, CAT, GPx and GSH) decreased. In addition, degeneration of hepatocytes and congestion in the central veins were observed. In contrast, in the groups administered Se and B with CP, the changes that occurred were reversed. However, it was found that Se protects the liver slightly better against CP damage than B. The protective effect of Se and B against the toxic effects of CP on the antioxidant markers SOD, CAT and GPx1 was also investigated in silico. The in silico results were consistent with the in vivo results for SOD and CAT, but not for GPx1.

Developing a multifunctional chitosan composite sponge for managing traumatic injuries

Developing porous hemostatic sponges that are both biosafe and multifunctional remains a complex challenge. Conventional hemostatic techniques often fall short in managing bleeding effectively, leading to severe critical cases such as suboptimal hemostasis, increased infection risk, and complications arising from profuse bleeding. To address these deficits, our study introduces a novel multifunctional nanocomposite sponge that synergistically incorporates chitosan (CS), cellulose (Cel), graphene oxide (GO), and silver (Ag) nanoparticles. The resulting CS/Cel/GO/Ag developed demonstrates a swelling rate exceeding 3000 %, an absorption rate of over 2100 %, and the lowest stress surpassing 20 kPa at an initial 80 % strain. In vitro analyses reveal that the CS/Cel/GO/Ag sponge has excellent cytocompatibility, non-hemolytic nature, and competence in blood cell adherence and bacterial inhibition. In vivo evaluations further demonstrate that compared to conventional hemostatic methods, the sponge substantially enhances hemostatic efficacy, as evidenced by the marked reductions in clotting times and diminished blood loss compared to conventional hemostatic methods. Specifically, the test results of the CS/Cel/GO/Ag sponge across three different models are as follows: for the rat tail amputation model, the clotting time was 99 s, while blood loss was 222 mg; for the rat liver injury model, the clotting time was 129 s. while blood loss was 812 mg; for the rat femoral artery laceration model, the clotting time was 96 s, while blood loss was 758 mg. The compelling attributes of the CS/Cel/GO/Ag sponges position them as a promising solution for the acute management of bleeding. Their excellent performance indicates they have potential role to play in trauma care.

Huangqi Decoction reduces liver fibrosis in rats by modulating PI3K/Akt/mTOR signaling and promoting autophagy.

Liver fibrosis is a chronic condition caused by various factors, and currently, there are no widely effective treatments. Autophagy plays a crucial role in maintaining liver energy homeostasis, and its disruption can contribute to the development of liver fibrosis. This study investigates the effects and molecular mechanisms of Huangqi Decoction, a traditional Chinese medicine, on autophagy and apoptosis in fibrotic liver tissue. Tissue staining indicated that Huangqi Decoction mitigated CCL4-induced liver injury and apoptosis in rats. Western blot analysis of liver fibrosis markers revealed that Huangqi Decoction significantly reduced the expression levels of alpha-smooth muscle actin (α-SMA), type I collagen, matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). Additionally, serum markers of liver fibrosis and biochemical indicators of hepatocyte injury showed that Huangqi Decoction effectively lowered serum levels of hyaluronic acid (HA), lymph node (LN), type I collagen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Furthermore, Western blot analysis confirmed that Huangqi Decoction alleviated hepatocyte injury by promoting autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway. In conclusion, Huangqi Decoction enhances autophagy and inhibits apoptosis through the PI3K/Akt/mTOR pathway in rats with liver fibrosis.

Assessment of Antioxidant and Hepatoprotective Effects of Kappaphycus alvarezii (Doty) Doty ex Silva Against Carbon Tetrachloride-Induced Liver Injury in Rats

Kappaphycus alvarezii (Doty) Doty ex Silva, commonly known as red algae, holds economic significance as a primary source of κ-carrageenan, which exhibits promising medicinal and therapeutic properties. This study aims to assess the antioxidant potential as well as hepatoprotective activity of the ethanolic extract of K. alvarezii (EEKA). The assays utilised to determine the antioxidant properties of EEKA were total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. In addition, the ability of EEKA to ameliorate experimentally induced liver injury in Sprague-Dawley rats caused by carbon tetrachloride (CCl4) was evaluated. The biochemical assays involved measuring liver marker enzymes (AST and ALT) in serum as well as determining the levels of reduced glutathione (GSH), lipid peroxidation (LPO) via malondialdehyde, catalase (CAT), and glutathione S-transferase (GST) in liver homogenates. The TPC and DPPH radical scavenging activity of EEKA demonstrated relatively low antioxidant properties compared to standard references. However, CCl4-induced groups exhibited significantly increased levels of AST and ALT, along with depletion of antioxidant status (GSH, CAT, and GST) indicated by LPO. Pretreatment with EEKA resulted in slightly decreased liver marker enzyme activity and LPO, coupled with an increase in antioxidant status. These findings suggest that EEKA contains active principles capable of counteracting the hepatotoxic effects induced by CCl4.

Small Molecule-Mediated Stage-Specific Reprogramming of MSCs to Hepatocyte-Like Cells and Hepatic Tissue for Liver Injury Treatment.

Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application. In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14days, while the GF-based protocol requires 23-28days. We optimized a stage-specific differentiation protocol for the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into functional hepatocyte-like cells (dHeps) that involved four stages, i.e., definitive endoderm (DE), hepatic competence (HC), hepatic specification (HS) and hepatic differentiation and growth. We further generated hepatic tissue using human decellularized liver extracellular matrix and compared it with hepatic tissue derived from the growth factor-based protocol at the transcriptional level. dHep, upon transplantation in a rat model of acute liver injury (ALI), was capable of ameliorating liver injury in rats and improving liver function and tissue damage compared to those in the ALI model. In summary, this is the first study in which hepatocytes and hepatic tissue were derived from MSCs utilizing a stage-specific strategy by exclusively using SM as a differentiation factor.

The protective effects of Acorus calamus L. rhizome extracts against rheumatoid arthritis-associated dyslipidemia, oxidative stress, and liver injury in rats

ABSTRACT Rheumatoid arthritis (RA) is associated with comorbidities like dyslipidemia and liver damage. Acorus calamus L. is commonly used to treat inflammatory and hepatorenal ailments. Herein, we assessed the hypolipidemic and hepatoprotective activities of A. calamus rhizome extracts in adjuvant-induced arthritis (AIA) in rats. A. calamus rhizome’s methanol (AME) and n-hexane (AHE) extracts were prepared. In vivo, fifty-four female Wistar rats were allocated into nine groups (n = 6). The AIA was induced by injecting Complete Freund’s adjuvant (100 µL, s.c.) into the rat’s right hind paw. After AIA induction, animals were orally treated with meloxicam (MEL; 3 mg/kg) and graded doses (125, 250, and 500 mg/kg) of AME and AHE for 28 consecutive days. Results showed that both plant extracts dose-dependently restored the body weight and liver index of arthritic rats. Each plant extract significantly (p < 0.05) attenuated hyperlipidemia and atherogenicity in arthritic rats. They also normalized the liver function markers and protein concentrations along with the reduction in hepatic oxidative stress. Histopathological examination of the liver supported the biochemical findings. However, AME exhibited better pharmacological activities than AHE. Our findings conclude that A. calamus rhizome could be used to treat dyslipidemia and liver injury in inflammatory conditions like RA.

A tough Janus poly(vinyl alcohol)-based hydrogel for wound closure and anti postoperative adhesion

Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m3; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m2 of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the in vivo adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation. Statement of significanceDespite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels.