Liver Injury In Rats Research Articles

Protective Effect of Herbal Medicinal Plant Extract against Carbon Tetrachloride Induced Liver Injury in Rat

Adiantum capillus (AC) Linn (Family: Adiantaceae) commonly known as “Hansraj” It is used in common cold, cough, pyrexia inflammation, acts as purgative. It improves digestion and renal function. This study was performed to investigate the hepato-defensive potential of Adiantum capillus in contradiction of carbon tetrachloride tempted hepatic damage in rats. The rodents were dosed with Acetonic extract (AEAC, 500mg/kg) extract of Adiantum capillus against Carbon Tetrachloride induced hepatic damage. Results shows thst Carbon Tetrachloride elevated the level of hepatic markers like SOPT, SGPT, bilirubin and ALP as well as altered the antioxidant enzymes. The level of hepatic biomarkers, as well as antioxidant enzyme, were recovered after the administration of at 500mg/kg, p.o., which was further confirmed by the histopathological. From above results it was concluded that The Acetonic extract (500 mg/kg, bw) extract of Adiantum capillus (ACE) recover the biochemical as well as antioxidant parameters, which were affected by Carbon Tetrachloride. The histopathological analysis supports the outcomes of antioxidants parameters.
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Standardized extract of Sanguisorba minor attenuates injury in aging rat model via the Nrf2/HO‑1 pathway.

Aging promotes damage to vulnerable organs like brain and liver. Sanguisorba minor has been traditionally used to cure various ailments. Few studies have reported pharmacological activities of this medicinal plant. This research aimed to investigate the effects of Sanguisorba minor extract (SME) on brain and liver injury in aging rats and identify the underlying mechanisms. The aging model was developed by subcutaneously injecting D‑galactose and simultaneously treating them with SME. After biochemical and pathological assessments, mRNA expression levels of nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) and Nrf2‑ regulated gene, heme oxygenase‑1 (HO‑1), in the brain and liver tissues were determined. As a result, malondialdehyde and acetylcholinesterase levels were elevated while total thiol content and superoxide dismutase were reduced in the aging rats. Treatment with the extract remarkably attenuated oxidative injury and pathological changes in liver and brain tissues. Concomitantly, the extract up‑regulated Nrf2 and HO‑1 genes. Our findings exhibited SME may improve the aging‑related brain and liver damage through the Nrf2‑HO‑1 pathway.

Hepatoprotective activity of lycopene in experimental paracetamol-induced liver injury in rats

Aim: To evaluate the hepatoprotective effects of lycopene pretreatment in paracetamol-induced liver damage (PILD). Methods: Wistar rats were administered oral lycopene (4 mg/kg/day) by gastric lavage for 8 days. Subsequently, 3 g/kg paracetamol was administered on day 8. After 24 and 72 h, animals were euthanized, and intracardiac blood samples were collected to measure levels of aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase, and alkaline phosphatase (ALP). In addition, the liver was harvested for histological analyses. Results: Negative and positive control groups (treated with saline or paracetamol on day 8, respectively) were compared with lycopene- and lycopene-paracetamol-treated (lycopene+paracetamol on day 8) groups. Notably, we observed that 24 h after PILD, lycopene treatment significantly reduced serum transaminase (ALT/AST) levels when compared with those in the saline-treated group. Conclusion: Lycopene improved liver recovery following PILD. Although lycopene exhibits antioxidant action and has been indicated for liver diseases, its use must be cautiously undertaken, especially considering the liver patholog y involved, as results may vary for each underlying factor.

Euryale ferox stem-inspired anisotropic quaternized cellulose/xanthan-based antibacterial sponge with high absorbency and compressibility for noncompressible hemorrhage

Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.

Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers but Fails to Restore Organ Function

We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H2 gas. Liver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H2 gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated. Portal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H2 groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H2 treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H2 group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H2 group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H2 groups. In conclusion, HMP and H2 gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.

Effect of the Non-steroidal Anti-inflammatory Drug Diclofenac on Ischemia-Reperfusion Injury in Rat Liver: A Nitric Oxide-Dependent Mechanism.

Ischemia/reperfusion injury (IRI) is an inevitable complication of liver surgery and transplantation. The purpose of this study was to examine the beneficial effects of diclofenac on hepatic IRI and the mechanism behind it. Wistar rats' livers were subjected to warm ischemia for 60min followed by 24h of reperfusion. Diclofenac was administered intravenously 15min before ischemia at 10, 20, and 40mg/kg body weight. To determine the mechanism of diclofenac protection, the NOS inhibitor L-Nitro-arginine methyl ester (L-NAME) was administered intravenously 10min after diclofenac injection (40mg/kg). Liver injury was evaluated by aminotransferases (ALT and AST) activities and histopathological analysis. Oxidative stress parameters (SOD, GPX, MPO, GSH, MDA, and PSH) were also determined. Then, eNOS gene transcription and p-eNOS and iNOS protein expressions were evaluated. The transcription factors PPAR-γ and NF-κB in addition to the regulatory protein IκBα were also investigated. Finally, the gene expression levels of inflammatory (COX-2, IL-6, IL-1β, IL-18, TNF-α, HMGB-1, and TLR-4) and apoptosis (Bcl-2 and Bax) markers were measured. Diclofenac, at the optimal dose of 40mg/kg, decreased liver injury and maintained histological integrity. It also reduced oxidative stress, inflammation, and apoptosis. Its mechanism of action essentially depended on eNOS activation rather than COX-2 inhibition, since pre-treatment with L-NAME abolished all the protective effects of diclofenac. To our knowledge, this is the first study demonstrating that diclofenac protects rat liver against warm IRI through the induction of NO-dependent pathway. Diclofenac reduced oxidative balance, attenuated the activation of the subsequent pro-inflammatory response and decreased cellular and tissue damage. Therefore, diclofenac could be a promising molecule for the prevention of liver IRI.

Sodium benzoate exacerbates hepatic oxidative stress and inflammation in lipopolysaccharide-induced liver injury in rats

Background Liver damage is a global health concern associated with a high mortality rate. Sodium benzoate (SB) is a widely used preservative in the food industry with a wide range of applications. However, there’s a lack of scientific reports on its effect on lipopolysaccharide-induced hepatic dysfunction. Objective The present study investigated the influence of SB on lipopolysaccharide (LPS)-induced liver injury. Materials and methods Twenty-eight rats were randomly allocated into four groups: control (received distilled water), SB (received 600 mg/kg), LPS (received 0.25 mg/kg), and LPS + SB (received LPS, 0.25 mg/kg, and SB, 600 mg/kg). SB was administered orally for 14 days while LPS was administered intraperitoneally for 7 days. Results Administration of SB to rats with hepatocyte injury exacerbated liver damage with a significant increase in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also observed that SB aggravated LPS-mediated hepatic oxidative stress occasioned by a marked decrease in antioxidant status with a concomitant increase in lipid peroxidation. Furthermore, LPS – mediated increase in inflammatory biomarkers as well as histological deterioration in the liver was exacerbated following the administration of SB to rats. Conclusion Taken together, the study provides experimental evidence that SB exacerbates hepatic oxidative stress and inflammation in LPS-mediated liver injury.

Therapeutic Efficacy of Anodonta cygnea and Crayfish Procambarus clarkii Hemolymph Extracts on Sepsis-Induced Acute Liver Injury in Neonate Rats

Therapeutic Efficacy of Anodonta cygnea and Crayfish Procambarus clarkii Hemolymph Extracts on Sepsis-Induced Acute Liver Injury in Neonate Rats

Study on the mechanism of acute liver injury protection in Rhubarb anthraquinone by metabolomics based on UPLC-Q-TOF-MS.

As a traditional Chinese medicine, rhubarb has been used in a variety of liver diseases and it is widely used in clinic to prevent and treat acute liver injury. Anthraquinone, as the main medicinal component of rhubarb, can reverse the further development of liver fibrosis caused by acute liver injury. In this study, metabonomics was used to explore the mechanism of different doses of rhubarb anthraquinone on acute liver injury in rats. Rhubarb anthraquinone was administered intragastric to rats at doses of 3.9, 7.8 and 15.6mg/kg, respectively, for 7days, and then 30% CCl4 was injected intraperitoneally at the dose of 1ml/kg to replicate the acute liver injury model. The biochemical indicators content of ALT, AST, ALP, γ-GT, TG, TC, LDL, HDL in serum and GSH, Hyp, SOD, TNF-α, IL-6 and IL-8 in liver tissue extract were tested respectively, and liver tissue was histopathologically analysis. At the same time, UPLC-Q-TOF-MS combined with non-targeted metabolomics were used to study the metabolites and metabolic pathways of rhubarb anthraquinone in treating acute liver injury. Compared with normal rats, the contents of ALT, AST, ALP, TG, TC, LDL, γ-GT in serum and Hyp, MDA, IL-6, IL-8, TNF-α in the liver tissue extract were significantly increased in model rats (p < 0.05, p < 0.01), and the content of HDL in the serum was significantly decreased (p < 0.05); the activities of GSH and SOD in liver tissue extract were also significantly decreased (p < 0.05). After administration of rhubarb anthraquinone, compared with the model group, with the increase of dosage, some biochemical indexes showed opposite changes, and gradually approached to normal rats. 12 different metabolites were identified by metabonomics, and the biosynthesis and metabolism of phenylalanine, tyrosine and tryptophan, the metabolism of amino sugars, nucleotide sugars and pyrimidines metabolism, and the biosynthesis of steroid hormone were identified based on the biomarker analysis. Based on the biochemical analysis and metabonomics analysis of rats with acute liver injury treated with different doses of rhubarb anthraquinone, combined with histopathological observation, the results show that the protective effect of rhubarb anthraquinone on acute liver injury is related to the dosage; Meanwhile, the metabolic pathway analysis suggested that rhubarb anthraquinone alleviate acute liver injury by regulating inflammation, oxidative stress and fibrosis disorders. This study explained the therapeutic effect of rhubarb anthraquinone on acute liver injury from both material basis and action pathway, and provided safe and effective research ideas for clinical application of rhubarb.

Protective effects of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1β signaling pathway

Baicalin magnesium is a water-soluble compound isolated from the aqueous solution by Scutellaria baicalensis Georgi. Preliminary experiments have demonstrated that baicalin magnesium can exert protective effects against acute liver injury in rats induced by carbon tetrachloride or lipopolysaccharide combined with d-galactose by regulating lipid peroxidation and oxidative stress. The aim of this study was to investigate the protective effect of baicalin magnesium on non-alcoholic steatohepatitis (NASH) in rats and to elucidate the underlying mechanisms. NASH was induced through a high-fat diet (HFD) for 8 weeks, and Sprague-Dawley rats were intravenously injected with baicalin magnesium, baicalin, and magnesium sulfate for 2 weeks, respectively. Serum was obtained for biochemical analyses and the determination of oxidative stress indicators. Liver tissues were collected for use in liver index assessment, histopathological examination, inflammatory factor analysis, and protein and gene expression analysis. The results revealed that baicalin magnesium markedly improved HFD-induced lipid deposition, inflammatory response, oxidative stress, and histopathological impairments. And baicalin magnesium may exert a protective effect on NASH rats by inhibiting the NLR family pyrin domain involving the 3 (NLRP3)/caspase-1/interleukin (IL)-1β inflammatory pathway. Additionally, the effect of baicalin magnesium was remarkably superior to that of equimolar baicalin and magnesium sulfate in regard to ameliorating NASH symptoms. In conclusion, the findings suggested that baicalin magnesium may represent a potential drug for the treatment of NASH.

Physiological and Histopathological Evaluation of the effect of Ethyl Caffeate on Carbon Tetrachloride (CCl4) Induced Liver Injury in Rats

The objective of the present work is to analyze the physiological and histopathological changes observed due to the effect of Ethyl caffeate, a polyphenol compound present in Solanum Nigrum fruits on CCl4 induced liver injury in male albino wistar rats. Thirty rats were used (5 groups, 6 animals per group). Group I is normal control given carboxymethyl cellulose (CMC), Group II is induction control given Carbon tetrachloride (CCl4), Group III (Standard control, Silymarin + CCl4), Group IV (Ethyl caffeate + CCl4) and Group V (Ethyl caffeate alone). At the end of 6 weeks, rats were sacrificed, physiological parameters (body weight, liver weight) were measured and histopathological observation of liver tissues was performed. From the physiological parameter results, body weight of group IV rats were increased (p&lt; 0.05) compared to group II. Enlargement of liver (hepatomegaly) is caused by CCl4 injury in group II (liver weight is increased), while the liver weight was reduced to near normal by ethyl caffeate treatment in group IV. Histolpathological analysis of Ethyl caffeate treated rats (group IV) showed less necrosis with mild periportal inflammation compared to group II rats. The findings of this work suggest that ethyl caffeate possess protective effect against liver injury against CCl4 based on the analysis of physiological and histopathological studies.

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake

Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/day of 56% (v/v) ethanol), three intervention groups with lutein (12, 24 and 48 mg/kg/day) and a positive control group (DG). The results showed that liver index, ALT, AST and TG levels were increased, and SOD and GSH-Px levels were reduced in the Et group. Furthermore, alcohol intake over a long time increased the level of pro-inflammatory cytokines TNF-α and IL-1β, disrupted the intestinal barrier, and stimulated the release of LPS, causing further liver injury. In contrast, lutein interventions prevented alcohol-induced alterations in liver tissue, oxidative stress and inflammation. In addition, the protein expression of Claudin-1 and Occludin in ileal tissues was upregulated by lutein intervention. In conclusion, lutein can improve chronic alcoholic liver injury and intestinal barrier dysfunction in rats.

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Beneficial effects of quercetin on vincristine-induced liver injury in rats: Modulating the levels of Nrf2/HO-1, NF-kB/STAT3, and SIRT1/PGC-1α.

Our experimental objective was to investigate the hepatotoxic effect of vincristine (VCR) administration in rats and determined whether combined therapy with Quercetin (Quer) ensured protection. Five groups with seven rats each were used for this purpose, and experimental groups were formulated as follows: Control group; Quer group; VCR group; VCR plus Quer 25 group; VCR plus Quer 50 group. The results showed that VCR significantly increased the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes. Besides, VCR caused considerable increases in the malondialdehyde (MDA) contents, along with significant decreases in reduced glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase enzyme activities in the rat livers. Quer treatment in VCR toxicity markedly decreased the activity of ALT, AST, ALP enzymes, and MDA contents and enhanced the activities of antioxidant enzymes. The results also showed that VCR significantly increased the levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3 and decreased the expression of Bcl2 and levels of Nrf2, HO-1, SIRT1, and PGC-1α. Compared to the VCR group, Quer treatment exhibited significantly lower levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3, and higher levels of Nrf2, HO-1, SIRT1, and PGC-1α. In conclusion, our study demonstrated that Quer could alleviate the harmful effects of VCR via activation of NRf2/HO-1 and SIRT1/PGC-1α pathways, and via attenuation of oxidative stress, apoptosis, autophagy, and NF-kB/STAT3 pathways.

Assessing Short-Term Vitamin E and C Treatment Effect in Paraquat Liver Poisoning

Paraquat has been considered as a toxicant in various countries, since it is not only intensely harmful but yet promptly accessible and generally cheap. Vitamin C and E are notable cancer prevention agents that respond rapidly to free radical and maximally forestall lipid peroxidation. The aim of this study was to evaluate the ameliorative impact of vitamin E and C in paraquat induced liver poisoning in rat. A total of 200 male wistar rats were obtained for the study. With 50 rats each, the rats were arranged into four grougs: A, B, C, and D. Each group was partitioned into two subgroups (0 and VEC), each with 25 rodents. The "A" group was not treated with paraquat, while the "B," "C," and "D" groups got 0.02g, 0.04g, and 0.06g of paraquat treatment respectively. All the "0" subgroups were those not treated with Vit E and C and all “VEC” subgroups were those treated with 500mg of vitamin E and 2000mg/dl of vitamin C. The paraquat treatment was administered once every 2 weeks for 3 months, followed by one month of week by week vitamin E and C treatment. Blood was drawn for SGPT, SGOT, ALP, and GGT testing. At p-value of 0.05, there was a significant increase in the activities of liver enzymes among the "A0", "B0", "C0", and "D0" groups. There was a significant decrease (P-value&lt;0.05) in the activities of liver enzymes in “VEC” subgroups. This study uncovered that vitamin E and C combined treatment ameliorated the Paraquat induced liver injury in rats.

Exploration of the anti-liver injury active components of Shaoyao Gancao decoction by network pharmacology and experiments in vivo

BackgroundShaoyao Gancao decoction (SGD), a classic traditional Chinese herbal formula, has been widely used to treat febrile diseases in the clinic for centuries. In recent years, a growing number of studies have found that SGD has a favorable anti-liver injury effect. PurposeIn this study, we want to know the potential active components of SGD treatment in liver injury. Study Design: A novel method combining computer simulation and in vivo experiment was established for the first time and used to investigate this problem. MethodsA network pharmacology was used to explore the active components of SGD treatment in liver injury, and preliminarily verified the results of network pharmacology through molecular docking. To further understand the active compounds of SGD in the treatment of liver injury, we compared the prototypes and metabolites of SGD in healthy rats and rats with liver injury after oral administration. In addition, a UPLC-MS/MS method was developed and successfully applied to investigate the pharmacokinetics of 9 compounds of SGD in healthy and liver injury rats. ResultsIt showed that SGD exerted protective effects against liver injury by the active components of liquiritin and albiflorin, etc. The values of the AUC0–t, AUC0-∞, t1/2, Tmax were significantly different after oral administration of SGD in healthy and liver injury rats. This indicates that the pharmacokinetic study in the pathological state of liver injury can provide more valuable information for guiding clinical medication. ConclusionIn this study, the integration of network pharmacology and experiments in vivo provides a novel strategy to explore active components of TCMs to treat diseases.

Exosomes derived from human adipose-derived stem cells alleviate hepatic ischemia-reperfusion (I/R) injury through the miR-183/ALOX5 axis.

Ischemia-reperfusion (I/R) injury is a crucial factor causing liver injury in the clinic. Recent research has confirmed that human adipose-derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of the effects of ADSCs in the treatment of liver injury remains unclear. The characteristics of ADSCs were first identified, and exosome-derived ADSCs were isolated and characterized. The function and mechanism of action of miR-183 and arachidonate 5-lipoxygenase (ALOX5) were investigated by functional experiments in HL-7702 cells with I/R injury and in I/R rats. Our data disclosed that exosome release from ADSCs induced proliferation and inhibited apoptosis in HL-7702 cells with I/R injury. The effect of miR-183 was similar to that of exosomes derived from ADSCs. In addition, ALOX5, as a target gene of miR-183, was involved in the related functions of miR-183. Moreover, in vivo experiments confirmed that miR-183 and exosomes from ADSCs could improve liver injury in rats and inhibit the MAPK and NF-κB pathways. All of these findings demonstrate that exosomes derived from ADSCs have a significant protective effect on hepatic I/R injury by regulating the miR-183/ALOX5 axis, which might provide a therapeutic strategy for liver injury.

Oliveria decumbens Extract Exhibits Hepatoprotective Effects Against Bile Duct Ligation-Induced Liver Injury in Rats by Reducing Oxidative Stress

Background: Cholestasis is described as a disease in which bile flow from the liver is reduced or stopped, and due to its oxidative effects, irreversible consequences may occur. Objectives: Due to the remarkable antioxidant properties of Oliveria decumbens (OD) and the contribution of oxidants to the progression of bile duct ligation (BDL)-induced cholestasis, this research aimed to examine how the OD ethanolic extract affected liver damage and oxidant-antioxidant balance markers in BDL-induced cholestasis. Methods: Forty male Wistar rats weighing 200 - 250 g were used. Cholestasis was induced using the BDL approach. The rats were categorized into four groups: Group 1, sham-control (SC); group 2, cholestatic; group 3, SC + OD; and group 4, cholestatic + OD. A dose of OD ethanolic extract was administered orally (500 mg/kg/day) to rats for seven days. Seven days following surgery, the rats’ blood samples were collected; after sacrifice, a part of the liver tissue was isolated. A histopathological examination was performed, while the rest was stored at -70°C in liquid nitrogen. Heparin-containing tubes were used to gather blood samples. In plasma and hepatic tissue, biochemical tests, histopathological evaluations, and oxidative stress markers staining levels were performed. Results: Our findings showed that OD could effectively reduce liver injury by reducing the activity of liver function enzymes (AST and ALP). At the same time, it did not affect total bilirubin and protein. Bile duct ligation-induced hepatic markers of protein oxidation (PCO) and reactive nitrogen species (NO) were significantly decreased by OD, and it also promoted liver antioxidant capacity by enhancing superoxide dismutase (SOD) activities. Moreover, OD treatment prevented liver bile duct proliferative changes in histopathologic analysis. Conclusions: Our study confirmed that OD exerts substantial hepatoprotective activities against BDL-induced cholestasis by improving liver damage markers and regulating oxidative stress. It may be a beneficial therapeutic agent for managing cholestasis. Bioassay-guided isolation and identification of bioactive OD secondary metabolites can further direct the discovery of potential natural-based drug candidates.

Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

Kaolin-loaded carboxymethyl chitosan/sodium alginate composite sponges for rapid hemostasis

There are several factors that contribute to the mortality of people who suffer from unmanageable bleeding. Therefore, the development of rapid hemostatic materials is necessary. Herein, novel rapid hemostatic composite sponges were developed by incorporation of kaolin (K) into carboxymethyl chitosan (CMCS)/sodium alginate (SA) via a combination of methods that includes ionic crosslinking, polyelectrolyte action, and freeze-drying. The CMCS/SA-K composite sponges were cross-linked with calcium ions provided by a sustained-release system consisting of D-gluconolactone (GDL) and Ca-EDTA, and the hemostatic ability of the sponges was enhanced by loading the inorganic hemostatic agent-kaolin (K). It was demonstrated that the CMCS/SA-K composite sponges had a good porous structure and water absorption properties, excellent mechanical properties, outstanding biodegradability, and biocompatibility. Simultaneously, they exhibited rapid hemostatic properties, both in vitro and in vivo. Significantly, the hemostatic time of the CMCS/SA-K60 sponge was improved by 82.76 %, 191.82 %, and 153.05 %, compared with those of commercially available gelatin sponges in the rat tail amputation, femoral vein, and liver injury hemorrhage models respectively, indicating that its hemostatic ability was superior to that of commercially available hemostatic materials. Therefore, CMCS/SA-K composite sponges show great promise for rapid hemostasis.