Liver Injury In Rats Research Articles

Study on the mechanism of enzymatically treated mulberry (Morus atropurpurea Roxb.) leaf protein relieves liver injury in heat stress rats

Heat stress (HS) can lead to oxidative stress and inflammatory responses, which jeopards animal production. Enzymatically treated mulberry leaf protein (ETMLP) has antioxidant activities and immune regulation. This study aimed to investigate the impacts of ETMLP on mitigate liver injury caused by heat stress in animals. All 25 rats were divided into five groups: control, heat stress, and three ETMLP supplementation groups (HS + 0.4 %, HS + 0.8 %, and HS + 1.2 %). ETMLP supplementation effectively reduced markers of liver damage and increasing the level of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px). It also regulated protein expression associated with stress response and antioxidant defense and suppressed pro-inflammatory proteins and pathways expression. Moreover, ETMLP improved intestinal morphology and increased the intestinal barrier gene abundance. ETMLP also positively influenced the intestinal microbiota by increasing beneficial microorganisms. Overall, ETMLP reversed heat stress-induced damage, improved growth performance, and regulated the intestinal microbiota in the study animals.

A bioactive composite sponge based on biomimetic collagen fibril and oxidized alginate for noncompressible hemorrhage and wound healing

The study focuses on developing a bioactive shape memory sponge to address the urgent demand for short-term rapid hemostasis and long-term wound healing in noncompressible hemorrhage cases. A composite sponge was created by spontaneously generating pores and double cross-linking under mild conditions using biomimetic collagen fibril (BCF) and oxidized alginate (OA) as natural backbone, combined with an inert calcium source (Ca) from CaCO3-GDL slow gelation mechanism. The optimized BCF/OACa (5/5) sponge efficiently absorbed blood after compression and recovered to its original state within 11.2 ± 1.3 s, achieving physical hemostatic mechanism. The composite sponge accelerated physiological coagulation by promoting platelet adhesion and activation through BCF, as well as enhancing endogenous and exogenous hemostatic pathways by Ca2+. Compared to commercial PVA expanding hemostatic sponge, the composite sponge reduced bleeding volume and shortened hemostasis time in rat liver injury pick and perforation wound models. Additionally, it stimulated fibroblast migration and differentiation, thus promoting wound healing. It is biodegradable with low inflammatory response and promotes granulation tissue regeneration. In conclusion, this biocomposite sponge provides multiple hemostatic pathways and biochemical support for wound healing, is biologically safe and easy to fabricate, process and use, with significant potential for clinical translation and application.

Facile Synthesis of Multifunctional Mesoporous Starch-Based Microparticle for Effective Hemostasis and Wound Healing.

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 μm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.

Effects of compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid on relative metabolic enzymes and various biochemical indices in Wistar rats with isoniazid-induced liver injury

Isoniazid (INH) is the first-line anti-tuberculosis drug in clinical practice, and its main adverse effect is drug-induced liver injury (DILI). This study aimed to investigate the hepatoprotective effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid (CAROL) and to provide a new strategy for the search of potential drugs against INH-induced liver injury in Wistar rats. Animal experiment was based on INH (100 mg/kg) induced liver injury to explore the intervention effects of CAROL at doses of 1.35, 2.70, and 5.40 mL/kg. LC-QTOF-MS/MS was used to identify hepatoprotective components in CAROL and its’ exposed components in rat serum. The hepatoprotective effect of CAROL was evaluated by pathological observation of rat liver tissue and changes in levels of biochemical indices and cytokines in serum or liver tissue. Of the 58 hepatoprotective components identified, 15 were detected in the serum of rats with liver-injured treated by high-dose CAROL. Results of animal experiments showed that the levels of various biochemical indexes and cytokines were significantly reversed with CAROL intervention. In particular, the expression level of cytokeratin-18 and high-mobility group box 1, as specific and sensitive indicators of DILI, was significantly reduced in the serum of rats with CAROL intervention compared with the INH model group. The same reversal was observed in the levels of TBIL, ALP, ALT, and AST in serum, as well as in the levels of TNF-α, IL-6, SOD, and MDA in liver tissue. For INH-metabolizing enzymes, an evident expression inhibition was observed in N-acetyltransferase 2 and glutathione S-transferases with CAROL intervention, which may be the key to controlling INH hepatotoxicity. CAROL has a favorable hepatoprotective effect on INH-induced liver injury. This study takes the first step in studying the hepatoprotective mechanism of CAROL against INH hepatotoxicity and provides reference for wider clinical applications.

Retraction Notice: "Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats".

Retraction Notice: "Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats".

Diclofenac Induced Hepatorenal Toxicity on Albino Rats: The Assessment of Mitigative Potential of Fermented Carica Papaya Juice

In a study investigating the protective effects of an extract on diclofenac-induced liver and kidney injuries in Wistar rats, twenty healthy adult Wistar rats weighing between 110g to 200g were randomly divided into four groups of five rats each. Group 1 Control group: received distilled water and standard feed, Group 2 Diclofenac group: administered 10mg/kg body weight of diclofenac., Group 3 Diclofenac + Pawpaw extract group: received diclofenac and post-treated with 200mg/kg body weight of fermented unripe Carica papaya juice, and Group 4 Pawpaw extract group: administered 200mg/kg body weight of fermented unripe Carica papaya juice. The plant extract and diclofenac were orally given over a duration of fourteen (14) days. After the treatment was finished, samples of blood and tissue were collected to analyze the liver function parameters (superoxide dismutase, catalase, and glutathione reductase) (Alanine aminotransferase - ALT, and alkaline phosphatase - ALP), renal function parameters (creatinine), oxidative stress markers, and for histological evaluation. The results showed that diclofenac administration caused a significant increase (p<0.05) in serum levels of ALT and ALP, creatinine and a significant decrease (p<0.05) in antioxidant enzymes (superoxide dismutase, catalase, and glutathione reductase) compared to the control group. However, treatment with FUPJ significantly reduced (p<0.05) the levels of ALT and ALP, creatinine, and MDA and increased (p<0.05) the levels of antioxidant enzymes. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced hepatic and renal dysfunction through its antioxidant and anti-inflammatory properties.

Study on mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site on CCl_4-induced chronic liver injury in rats

This study aims to investigate the mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site(CGE) on the disease in carbon tetrachloride(CCl_4)-induced chronic liver injury model in rats. A chronic liver injury model was constructed by subcutaneous injection of CCl_4 olive oil solution, and after four weeks of CGE treatment, serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(AKP), hydroxyproline(HYP), interleukin-4(IL-4), interleukin-6(IL-6), malondialdehyde(MDA), superoxide dismutase(SOD), and tumor necrosis factor-α(TNF-α) were detected. Liver tissue was processed by hematoxylin-eosin(HE) staining and Masson staining to observe the structure of the rat liver. qPCR and Western blot were used to examine the expression of transforming growth factor-β1(TGF-β1)/small mothers against decapentaplegic(Smad), Toll-like receptor 4(TLR4), α-smooth muscle actin(α-SMA), and fibronectin(Fn) in rat liver tissue and hepatic stellate-T6(HSC-T6) and evaluate the inhibitory effect of CGE on HSC activation. The results showed that CGE could significantly reduce the serum levels of AST, ALT, AKP, HYP, and affect the levels of related inflammatory indexes including IL-4, IL-6, and TNF-α, and MDA in CCl_4-induced chronic liver injury in rats and had no effect on SOD activity, which could delay the process of liver injury, alleviate the hepatic collagen deposition and inflammatory infiltration, and had significant efficacy in mitigating chronic liver injury in rats. CGE could inhibit α-SMA and TLR4 protein expression in the liver tissue and reverse the increased TGF-β1/Smad, Fn, and TLR4-related expression in HSC-T6 in vitro. The above results indicated that CGE exerted hepatoprotective effects in rats by inhibiting HSC activation and alleviated CCl_4-induced chronic liver injury in rats and could ameliorate inflammatory response and slight liver fibrosis in rat liver tissue. Its pharmacodynamic mechanism might be related to TGF-β1/Smad and TLR4-related expression.

Acute Toxicity and Hepatoprotective Influence of Hypericum perforatum Against Thioactamid-Induced Liver Fibrosis in Rats

Background: Hypericum perforatum (MEHP) is a broadly used therapeutic plant exhibiting numerous bioactivities. The present study evaluates acute toxicity and hepatoprotective effects of MEHP against thioacetamide (TAA)-induced liver injury in rats. Methods: The toxicity trial included a single oral administration of 2000 and 5000 mg/kg to rats. In the hepatoprotective experiment, 30 adult rats were arbitrarily clustered into 5 groups: Normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received 3 oral doses/week of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEHP, respectively. In addition, group B-E received 3 injections of 200 mg/kg TAA in a week for 60 days. Results: The results have shown a lack of any toxic signs in rats following oral administration of up to 5000 mg/kg. The hepatoprotective evaluations revealed a noticeably lower hepatic injury in MEHP-treated rats shown by reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&E and Masson trichrome stains) showed a significant inhibitory potential of MEHP on the incidence rate of hepatic lesions represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEHP treatment meaningfully decreased proliferating cell nuclear antigen and α-SMA (myofibroblasts) in liver parenchymal tissues as well as improved redox (up-regulated SOD, CAT, GPx, and down-regulated MDA) and inflammatory state (decreased serum TNF-α and IL-6 cytokines) compared to fibrosis control rats. In addition, MEHP treatment caused significant restoration of serum liver biomarkers (enzymes and proteins) against TAA-induced hepatotoxicity. Conclusion: The present hepatoprotectives of MEHP could be attributed to its chemical contents (hypericin, hyperforin, quercitrin, and p-coumaric acid) that may validate it as a therapeutic additive for liver fibrosis after some pharmacological evaluations.

Concurrent alteration in the inflammatory biomarkers at gene and protein level by fucoxanthin in liver injury rat

Concurrent alteration in the inflammatory biomarkers at gene and protein level by fucoxanthin in liver injury rat

Development of an efficient hemostatic material based on cuttlefish ink nanoparticles loaded in cuttlebone biocomposite.

Traumatic hemorrhage is one of the main causes of mortality in civilian and military accidents. This study aimed to evaluate the effectiveness of cuttlefish bone (cuttlebone, CB) and CB loaded with cuttlefish ink (CB-CFI) nanoparticles for hemorrhage control. CB and CB-CFI were prepared and characterized using different methods. The hemostasis behavior of constructed biocomposites was investigated in vitro and in vivo using a rat model. Results showed that CFI nanoparticles (NPs) are uniformly dispersed throughout the CB surface. CB-CFI10 (10 mg CFI in 1.0 g of CB) showed the best blood clotting performance in both in vitro and in vivo tests. In vitro findings revealed that the blood clotting time of CB, CFI, and CB-CFI10 was found to be 275.4 ± 12.4 s, 229.9 ± 19.9 s, and 144.0 ± 17.5 s, respectively. The bleeding time in rat liver injury treated with CB, CFI, and CB-CFI10 was 158.1 ± 9.2 s, 114.0 ± 5.7 s, and 46.8 ± 2.7 s, respectively. CB-CFI10 composite resulted in more reduction of aPTT (11.31 ± 1.51 s) in comparison with CB (17.34 ± 2.12 s) and CFI (16.79 ± 1.46 s) (p < 0.05). Furthermore, CB and CB-CFI10 exhibited excellent hemocompatibility. The CB and CB-CFI did not show any cytotoxicity on human foreskin fibroblast (HFF) cells. The CB-CFI has a negative surface charge and may activate coagulation factors through direct contact with their components, including CaCO3, chitin, and CFI-NPs with blood. Thus, the superior hemostatic potential, low cost, abundant, simple, and time-saving preparation process make CB-CFI a very favorable hemostatic material for traumatic bleeding control in clinical applications.

Eggshell membrane powder reinforces adhesive polysaccharide hydrogels for wound repair

Multifunctional polysaccharide hydrogels with strong tissue adhesion, and antimicrobial and hemostatic properties are attractive wound healing materials. In this study, a chitosan-based hydrogel (HCS) was designed, and its properties were enhanced by incorporating oxidized eggshell membrane (OEM). Hydrogel characterization and testing results showed that the hydrogel had excellent antimicrobial properties, cytocompatibility, satisfactory adhesion properties on common substrates, and wet-state adhesion capacity. A rat liver injury model confirmed the significant hemostatic effect of the hydrogel. Finally, the ability of the hydrogel to promote wound healing was verified using rat skin wound repair experiments. Our findings indicate that HCS/OEM hydrogels with added eggshell membrane fibers have better self-healing properties, mechanical strength, adhesion, hemostatic properties, and biocompatibility than HCS hydrogels, in addition to having superior repair performance in wound repair experiments. Overall, the multifunctional polysaccharide hydrogels fabricated in this study are ideal for wound repair.

Histological and Immunohistochemical Studies on the Effect of Curcumin Nanoparticles versus Mesenchymal stem cells on Acetaminophen-Induced Acute Liver injury in Adult Male Albino Rats

Histological and Immunohistochemical Studies on the Effect of Curcumin Nanoparticles versus Mesenchymal stem cells on Acetaminophen-Induced Acute Liver injury in Adult Male Albino Rats

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAβO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

Experimental study on the inhibition of the NLRP3 signaling pathway with Shengsan Jiedu Huayu decoction to alleviate inflammatory injury in rats with acute-on-chronic liver failure

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1β content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1β, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1β and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1β, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1β, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 μm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

A super hydrophilic and high strength chitosan hemostatic sponge prepared by freeze-drying and alkali treatment for rapid hemostasis

Excessive blood loss caused by natural accidents or major surgical procedures can be life-threatening and requires rapid hemorrhage management. Developing hemostatic materials with high water absorption capacity and high strength properties is still challenging. Super hydrophilic/high-strength chitosan hemostatic sponges (SHHS-CHS) were prepared by freeze-drying and alkali treatment. The freeze-drying technology formed a porous three-dimensional structure of sponges, and alkali treatment increased the hydrophilicity of sponges and the rigidity of the chitosan molecular chain, improving the hydrophilicity and mechanical properties of chitosan sponges. Characterization experiments revealed that SHHS-CHS had high water absorption capacity, rich pore structure, and excellent mechanical properties. The cytotoxicity and hemolysis experiments showed that SHHS-CHS had good biocompatibility. Compared to the commercial hemostatic gelatin sponges and chitosan hemostatic material, SHHS-CHS had better blood coagulation and red blood cell and platelet adhesion ability. Moreover, SHHS-CHS showed better hemostatic ability than gelatin sponges in rat-liver injury and rat leg vein rupture models, significantly reducing the hemostasis time and bleeding volume. In conclusion, SHHS-CHS has broad prospects for clinical application as a hemostatic material.

Novel pH-sensitive triptolide-loaded micelles: a potential approach to increase anti-tumor activity of the diterpenoid epoxide

Tripterygium wilfordii Hook F, a traditional medicine in China has bioactive but toxic triptolide (TP, a diterpenoid triepoxide) as its main active constituents. The applications of TP are hampered by its prominent toxicity and low solubility in water. In this study, a safe pH-sensitive material [methoxy polyethylene glycol (mPEG)- adipic dihydrazide (ADH)] was synthesized and loaded with TP to form pH-sensitive polymeric micelles, thereby improving the safety and solubility of TP, as well as providing a theoretical basis for the wide application of TP. The mPEG-ADH/TP micelles were characterized by a series of indicators [namely entrapment efficiency (EE), critical micellar concentration (CMC), electrokinetic potential, stability, polydispersed index (PDI), and particle size]. Also, we ascertained the in vitro release of TP from mPEG-ADH/TP micelles along with pharmacokinetic investigations in vivo. Besides, we evaluated the cytotoxicity of mPEG-ADH/TP micelles against A549 cells, HCT116 cells, and HaCat cells and further conducted in vivo toxicity studies in rats. The TP-loaded mPEG-ADH micelles had smaller sized particles (48.3 nm), excellent PDI (0.142), stable property and higher EE (89.87%). Importantly, the TP in the mPEG-ADH/TP micelles was almost completely released at acidic pH (pH 5.0), while the drug was released slowly and sparingly at physiological pH (pH 7.4). The results suggest the release of TP from mPEG-ADH/TP micelles was sensitive to pH, which could facilitate targeting of the drug into intra-cellularly low pH endosomes and lysosomes as well as enhance cytotoxicity in cancer tissues. Moreover, mPEG-ADH/TP micelles exhibited excellent proliferation inhibition on tumor cells. In addition, the liver injury of rats in the 1 mg/kg dose of mPEG-ADH/TP micelles group was significantly reduced by Hematoxylin–eosin (HE) staining. Taken together, mPEG-ADH/TP micelles could act as a promising alternative to enhance the efficacy of oncologic treatments.

Hepatoprotective Activity of Ezetimibe Against Risperidone-Induced Liver Injury in Rats

Abstract Background: Drug-induced hepatic injury is an unfavorable reaction to medications and/or their byproducts, which can result in ongoing harm to liver function and even death. Risperidone, the second most prescribed antipsychotic drug, has been linked to weight gain, abnormal hepatic enzyme levels, and further damage to liver cells. On the other hand, ezetimibe is an antihyperlipidemic agent that reduces serum cholesterol levels by inhibiting its absorption in the gastrointestinal tract. Additionally, it possesses antioxidant, hepatoprotective, and nephroprotective properties. Objectives: The purpose of this study is to evaluate the hepatoprotective and hypolipidemic effects of ezetimibe in mitigating liver damage induced by risperidone. Materials and Methods: A total of 24 adult male Swiss albino rats aged 6–7 weeks and weighing 170–180 g each were randomly divided into four groups, with 6 rats in each group. The first group served as a control and received vehicles only (0.5 mL of corn oil). Rats in the second group were administered risperidone alone at a dose of 2 mg/kg. In the last two groups, rats received a combination of risperidone (2 mg/kg) and ezetimibe at doses of 3 and 5 mg/kg, respectively. After sacrificing the rats, serum samples were collected to measure parameters related to lipid profile and liver enzymes. Additionally, liver tissue was immediately gathered for histopathological assessment using the NAS scoring system. Results: Ezetimibe exhibited marked hepatoprotective effects in rats exposed to risperidone-induced hepatic injury. This was achieved by significantly (P &lt; 0.05) lowering adverse lipid profile components (TCHO, TG, LDL, and VLDL) and liver enzymes (ALT and AST), while at the same time significantly (P &lt; 0.05) elevating the beneficial lipid profile (HDL). Moreover, Ezetimibe demonstrated remarkable liver protection by mitigating hepatic lobule destruction, inflammatory cell infiltration, and the presence of steatotic cells. Conclusion: Ezetimibe exhibited notable hepatoprotective and hypolipidemic properties in countering hepatic injury induced by risperidone.

Effects of Garnoderma lucidum on Acetaminophen-Induced Liver Injury in Wistar Rats

Introduction: Ganoderma lucidum is considered to be a medicinal mushroom, widely used to prevent or treat different types of diseases including cancer, cardiovascular disease and hepatic dysfunction. This study aimed to evaluate the effect of Ganoderma lucidum on acetaminophen-induced liver injury in wistar rats. Methods: Forty (40) male wistar rats were used for this study. Hepatoxicity was induced by oral administration of acetaminophenn (3000 mg/kg of body weight) for the last 21 consecutive days of the dietary of regimen Ganoderma lucidum. These rats were divided into eight cages each containing Five rats. Control Group 1 fed on feed and water only throughout the study, Group 2 received acetaminophen only, Group 3 received Acetaminophen + Standard drug (silymarin), Group 4 received Acetaminophen +100 mg/kg body weight of Ganoderma lucium extract, Group 5 received Acetaminophen + 200 mg/kg body weight of Ganoderma lucidum extract, Group 6 received Acetaminophen + 300 mg/kg body weight of Ganoderma lucidum extract , Group 7 received 100 mg/kg of Ganoderma lucidum extract, Group 8 received Acetaminophen+Standard Drug (silymarin) + 300 mg/kg body weight of Ganderma lucidum extract. Blood samples was collected via cardiac puncture within 24 hours of Sacrifice. The extent of the liver injury was determined by assessing the plasma levels of Tumor Necrosis Factor Alpha (TNF-α), Alpha Feto protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin (TB), Conjugated bilirubin (CB), Unconjugated Bilirubin (UB), Albumin, Gamma Glutamyl Transaminase (GGT) and total protein (TP) using spectrophotometric method and ELISA as appropriate. Results: Oral administration of Acetaminophen significantly increased the plasma levels of the parameters accessed, suggesting severe liver damage in the rats. However, the treatment of Ganoderma lucidum decreased these hepatotoxic indices at a significant level of P &lt;0.01 for TNF-α, AFP, ALT, AST, UB, TB, GGT and ALP, while Albumin and Conjugated Bilirubin were significantly decreased at a level of (P&lt;0.05) in the Ganoderma lucidum + Acetaminophen-administered group compared to those of the control group. Conclusion: Thus, the results of the present investigation demonstrates that the Ganoderma lucidum provides significant hepatoprotective activity against acetaminophen-induced liver injury in wistar rats.

Augmented reparative potential of adipose-derived stem cells with silver nanoparticles against CCl4-induced liver injury in rats

Cymbopogon citratus (lemongrass) is a widely used medicinal plant. The previous literature studies demonstrated its diverse pharmacological activities such as anti-inflammatory, anti-diabetic, antibacterial and antifungal properties. The present study involves the green synthesis of silver nanoparticles from lemongrass and their characterization by X-ray diffraction (XRD), scanning electron microscope (SEM) and Fourier transmission infrared (FTIR). The purpose of this study is to evaluate the hepatoprotective potential of silver nanoparticles derived from the aqueous extract of lemongrass (LG-NPs) in comparison with the rat adipose-derived mesenchymal stem cells (ASCs) treated with lemongrass-derived silver nanoparticles (LG-NPs + ASCs). To assess the hepatoprotective effect of LG-NPs + ASCs, CCl4-induced fibrosis model rats were employed and it was revealed that transplanting LG-NPs + ASCs decreased fibrosis development compared to transplanting naive ASCs and LG-NPs, as demonstrated by improved hepatic architecture and functions. Additionally, the liver parenchyma's expression of fibrosis-associated gene markers Interleukin 1 beta (IL-1β), Cytochrome P450 2E1 (CYP2E1), Transforming Growth Factor Beta 1 (TGF-β1), collagen type I alpha 1(Col1α1), α-smooth muscle actin (α-SMA) reduced after LG-NPs + ASCs transplantation. These results suggest that pretreating ASCs with LG-NPs increase their effectiveness.