Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses.

The escalating global burden of cardiovascular diseases is a growing concern. Numerous research studies have established that plant-derived polyphenols, including α-pinene-a monocyclic monoterpene found in various plant essential oils-have significant effects on key cardiovascular mechanisms. These effects are mediated through their influence on antioxidant systems, cellular signaling pathways, and gene transcription processes. This study investigated the protective effects of α-pinene against cardiac damage caused by carbon tetrachloride (CCl4) in Wistar rats. Rats were divided into four groups: a control group receiving saline, a disease control group-administered CCl4 (1 mL/kg body weight, intraperitoneally), and two treatment groups receiving α-pinene orally at doses of 50 mg/kg and 100 mg/kg body weight alongside CCl4, to assess its dose-dependent effects. We conducted comprehensive evaluations, including assessments of serum and cardiac toxicity biomarkers, inflammatory mediators, antioxidant defense mechanisms, lipid peroxidation levels, lipid profiles, and histopathological analyses. CCl4 exposure resulted in notable increases in free fatty acids (FFA), total cholesterol (TC), triglycerides (TG), phospholipids (PL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels, and a decrease in high-density lipoprotein (HDL) levels. Treatment with α-pinene at 100 mg/kg effectively counteracted these lipid profile changes. CCl4 also caused lipid oxidation and a reduction in antioxidant activities, which were restored to normal levels with α-pinene treatment at 100 mg/kg body weight. Moreover, an upsurge in inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (Hs-CRP)) and cardiac toxicity biomarkers (creatine kinase (CK), and creatine kinase-myocardial band (CK-MB) and troponin) induced by CCl4 intoxication was reversed by α-pinene. Histopathological studies further validated these findings. The study concludes that α-pinene, administered at a dosage of 100 mg/kg body weight, effectively alleviates cardiac injury induced by CCl4. The data suggest that α-pinene exerts its protective effects through modulation of various signaling pathways involved in CCl4-induced cardiac toxicity.

Hepatoprotective efficacy of Lagenaria siceraria seeds oil against experimentally carbon tetrachloride-induced toxicity.

Background: The liver is crucial for maintaining normal metabolism in the body. Various substances, such as toxic chemicals, drugs, and alcohol, can damage hepatocyte cells, leading to metabolic imbalances. Aim: The experiment aimed to determine the efficacy of Lagenaria siceraria seed oil (LSS) as a hepatoprotective agent against acute hepatotoxicity triggered by carbon tetrachloride (CCl4). Methods: A total of 20 rats were randomly separated into four groups. The control group: rats received 2 ml of distilled water orally, followed by 1.25 ml of olive oil intraperitoneally (i.p.) after 30 minutes. CCL4 group: rats were given a single intraperitoneal dose of 1.25 ml/kg b.w. of CCl4 in a 1:1 mixture with olive oil. Silymarin group: received 100 mg of silymarin per kg of b.w. diluted in 2 ml of distilled water orally, followed by CCl4 treatment after 30 minutes. LSS oil group: received LSS oil at 3g/kg b.w. orally, followed by CCl4 treatment after 30 minutes. Blood samples were collected to assess liver enzymes (AST, ALT, and ALP), proteins and bilirubin fractions, and redox status (catalase, reduced glutathione (GSH), and malondialdehyde (MDA)) were assessed in hepatic tissues. Changes in liver histopathological examination were also evaluated. Results: In CCl4-treated rats, there was a significant increase in serum liver marker enzyme activity (ALP, AST, and ALT) along with a significant elevation (p < 0.05) in total bilirubin, indirect bilirubin, and direct bilirubin compared to the control rats. However, all these parameters decreased in the CCl4+ Silymarin and CCl4+LSS groups compared to CCl4-treated rats. There was a significant decline in total protein level and serum albumin in all experimental groups compared to the control, while globulin levels significantly increased in all experimental groups. There was a significant (p < 0.05) reduction in the level of GSH and catalase, with an increase in MDA level in CCl4 rats compared to other rats. Histopathological investigation of the LSS-treated group showed a hepatoprotective effect against CCl4. Conclusion: The study revealed that LSS oil has antioxidant activity against CCl4-induced toxicity.

Echinacoside Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Modulating the NF-κB/NLRP3 Inflammasome Pathway.

The purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)-induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague-Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose-dependent manner. Ech effectively mitigated CCL4-induced chronic liver injury in rats by downregulating the NF-κB/NLRP3 inflammasome pathway.

Beta-caryophyllene attenuates experimental hepatocellular carcinoma through downregulation of oxidative stress and inflammation.

Hepatocellular carcinoma (HCC) is caused by various factors including toxic substances and xenobiotics. Numerous treatment strategies are used to address toxicity to the liver and HCC, yet their adverse effects are drawbacks. This study aimed to assess the effect of DEN/CCl4 on morphological changes in the liver, body weight, tumor incidence, and hematological tumor incidence, hematological parameters, hepatic markers, and histopathological analysis in mice following a preventive measure by using ß-caryophyllene (BCP). Adult Balb/c mice were administered a single dose of DEN 1-mg/kg body weight and 0.2-mL CCl4/kg body weight intraperitoneal twice a week (i.p.) for 22 weeks. BCP was treated in one group of mice at 30-mg/kg body weight, intraperitoneal, for 7 weeks. BCP alone was treated in one group of mice at 300-mg/kg body weight intraperitoneal for 22 weeks. DEN/CCl4 caused a reduction in mice's body weight, which was significantly attenuated by BCP administration. BCP supplementation attenuated the tumor incidence DEN/CCl4 (100%) to about 25%. DEN/CCl4 caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (AST, ALT, ALP, GGT, ACP, and bilirubin), and lipid profile markers that were significantly reinstated by BCP administration. Oxidative stress markers (MDA, SOD, CAT, NO, LDH, and GST) were reduced by DEN/CCl4, which were significantly increased in BCP-treated groups. The liver histopathology alterations caused by DEN/CCl4 were amended considerably by BCP treatment. Immunohistochemical studies suggest that AFP, caspase-3, and COX-2 were chronically overexpressed in DEN/CCl4-exposed mice, notably attenuated by BCP administration. BCP suppressed tumor incidence by downregulating inflammation and inducing caspase-3-mediated apoptosis. Conclusively, BCP appears to be a potent natural supplement capable of repressing liver inflammation and carcinoma through the mitigation of oxidative stress and inflammation pathways.

Protective effect of sinomenine against CCl4-induced acute liver injury through regulation of mitochondrial biogenesis.

Carbon tetrachloride (CCl4)-provoked acute liver injury (ALI) is typified by intensified apoptotic, inflammatory, and oxidative changes besides mitochondrial dysfunction. Sinomenine is an active constituent in the medicinal plant Sinomenium acutum. The main objective of this study was to determine sinomenine-induced hepatoprotection following CCl4 challenge with an emphasis on unraveling the contribution of mitochondrial biogenesis-related factors. To induce ALI, CCl4 was injected i.p. and sinomenine was orally administered at 10, 25, and 50 mg/kg. Serum factors in relation to liver dysfunction were measured in addition to hepatic analysis of apoptotic, mitochondrial biogenesis, oxidative, and inflammatory parameters. Sinomenine pretreatment significantly lowered ALT and AST, MDA, IL-6, apoptosis intensity, and TNF-α and restored mitochondrial biogenesis besides enhancement of SOD, sirtuin-1, and AMPK. Sinomenine also conferred hepatoprotective impact, as was apparent by lower pathologic changes. These effects were accompanied by changes in gene expression for AMPK/sirtuin-1/PGC-1α/PPARγ. The current study showed sinomenine hepatoprotective impact in CCl4-induced ALI that is associated with its regulation of mitochondrial biogenesis and parallel enhancement of AMPK/sirtuin-1.

Peripheral serum iTRAQ-based proteomic characteristics of carbon tetrachloride-induced acute liver injury in Macaca fascicularis.

Carbon tetrachloride (CCl4) is a potent chemical compound that can induce liver cells necrosis. The purpose of this study was to evaluate the hepatic toxicity of CCl4 exposure in Macaca fascicularis to explore the liver toxicity mechanism using a proteomic approach. One animal (no.F6) was intoxicated by oral gavage with 15 % CCl4 solution (10 mL/kg, dissolved in edible peanut oil), and was sacrificed at 48 h after CCl4 administration. Another blank control animal (no.F4) was sacrificed at the same time. The liver cells of the blank control animal showed normal hepatocyte morphology. However, the hepatocytes at 48 h time point after CCl4 administration showed necrosis and vacuolation histopathologically. The animal No.F7∼F12 and no.M7∼M12 were administrated by gavage with 15 % CCl4 solution (10 mL/kg, dissolved in edible peanut oil). Blood samples were collected before gavage administration, and served as the 0 h blank control samples. Then, blood samples were collected at 2 h, 48 h, 72 h and 168 h after CCl4 exposure, and served as the test samples. Routine biochemistry and immunical parameters were performed using biochemistry analyzer for all serum. Then the serum from male and female animals at 0 h, 2 h, 48 h, and 72 h was mixed, respectively. The peripheral serum proteins at 0 h, 2 h, 48 h, and 72 h were extracted, then the proteins were enzymatically hydrolyzed and the peptides were isotopic labeled by isobaric tags for relative and absolute quantification (iTRAQ). Finally, the UniProt Protein Sequence Library of Macaca fascicularis was queried to identify and compare the differential proteins between different time points. The results showed that, as traditional biomarkers of liver injury, alanine aminotransferases (ALT) and aspartate aminotransferases (AST) showed a typical time-effect curve. Compared with 0 h, there were totally 55, 323, and 158 differential proteins (P value <0.05, Ratio fold >1.5, FDR<0.05) at 2 h, 48 h and 72 h, respectively. GO enrichment analysis of differentially expressed proteins only at 48 h involved 3 cellular components (P adjust value <0.05), and differential proteins at other time points had no significant enrichment. Furthermore, KEGG enrichment analysis showed that the toxicity effect of CCl4 at different time points after administration was mediated through 22 pathways such as biosynthesis of antibiotics, carbon metabolism, biosynthesis of amino acids, peroxisome, cysteine and methionine metabolism, arginine biosynthesis, and complement and coagulation cascades (P adjust value <0.05). Among them, the counts of signaling pathway involved biosynthesis of antibiotics, carbon metabolism and biosynthesis of amino acids were more than 10 and the three pathways may play a greater role in toxicity progress after administration of CCl4. PPI network analysis showed that there were 3, 52, and 13 nodes in the interaction of differential proteins at 2 h, 48 h, and 72 h, respectively. In conclusion, many differential proteins in peripheral blood were detected after CCl4 administration, and the GO and KEGG enrichment analysis showed the toxicological mechanisms of CCl4-induced liver injury and potential protection reaction mechanism for CCl4 detoxication may be related with multi biological processes, signaling pathway and targets.

Cereblon deficiency ameliorates carbon tetrachloride-induced acute hepatotoxicity in HepG2 cells by suppressing MAPK-mediated apoptosis.

The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway. Cereblon (CRBN), a multifunctional protein implicated in various cellular processes, functions in the pathogenesis of various diseases; however, its function in liver injury remains unknown. We established a CRBN-knockout (KO) HepG2 cell line and examined its effect on CCl4-induced hepatocellular damage. CRBN-KO cells exhibited reduced sensitivity to CCl4-induced cytotoxicity, as evidenced by decreased levels of apoptosis markers, such as cleaved caspase-3, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. CRBN deficiency enhanced antioxidant defense, with increased superoxide dismutase activity and glutathione ratios (GSH/GSSG), as well as reduced pro-inflammatory cytokine expression. Mechanistically, the protective effects of CRBN deficiency appeared to involve the attenuation of the MAPK-mediated pathways, particularly through decreased phosphorylation of JNK and ERK. Overall, these results suggest the crucial role of CRBN in mediating the hepatocellular response to oxidative stress and inflammation triggered by CCl4 exposure, offering potential clinical implications for liver injury in a wide range of liver diseases.

Zanthoxylum zanthoxyloides (Lam.) B. Zepernick & Timler alkaloidal extract exerts hepatoprotective effects in rats with a CCl4/olive oil-induced hepatocellular carcinoma-like phenotype.

Objective: This study assessed the prophylactic anti-HCC effects of a combined stem and root alkaloidal extract of Zanthoxylum zanthoxyloides (Z. zanthoxyloides) (SRAEZZ) in rats with a CCl4/olive oil-induced HCC-like phenotype. Methods: SRAEZZ was prepared from dried stems and roots of Z. zanthoxyloides in a 1:1 proportion and chemically characterized. A total of 30 healthy male Wistar rats (weighing 210-280 g) were randomly assigned to six groups (control, model, capecitabine, and SRAEZZ [50, 100, or 200 mg/kg]). All groups except the control received CCl4/olive oil (3 mL/kg, po) in the morning, whereas in the afternoon of the same dosing day, the model group received normal saline (5 mL/kg, po), the capecitabine group received capecitabine (50 mg/kg, po), and the SRAEZZ groups received SRAEZZ (50, 100, or 200 mg/kg, po, respectively) once per week for 36 days. Survival rate, serum α-fetoprotein (AFP), and C-reactive protein (CRP) were monitored. Gross liver anatomy, liver histology, liver enzymes (ALP, AST, and ALT), bilirubin, creatinine, urea, albumin, globulins, and hematological parameters were assessed. Results: SRAEZZ yield was 0.58% from the initial stem and root sample (520 g). Quaternary phenanthridin alkaloids were detected in SRAEZZ. Control rats had a 100% survival rate compared with rats in the model group. SRAEZZ treatment improved the survival rate with respect to that in the model group. Serum AFP, CRP, and bilirubin levels were greater in the model group than the control group. SRAEZZ decreased serum AFP, CRP, and bilirubin below the levels observed in the model group. ALP, AST, and AST were higher in the model group, but lower in SRAEZZ-treated group, than the control group. Conclusion: SRAEZZ demonstrated prophylactic anti-HCC effects against CCl4/olive oil-induced HCC-like phenotypes in rats. These findings highlight the potential of crude alkaloids from Z. zanthoxyloides as natural templates for semi-synthesis of anti-HCC pharmacotherapeutics.

High-Fat Diet Delays Liver Fibrosis Recovery and Promotes Hepatocarcinogenesis in Rat Liver Cirrhosis Model.

More effective treatments for hepatitis viral infections have led to a reduction in the incidence of liver cirrhosis. A high-fat diet can lead to chronic hepatitis and liver fibrosis, but the effects of lipid intake on liver disease status, including hepatitis C virus and alcohol, after elimination of the cause are unclear. To investigate the effects, we used a rat cirrhosis model and a high-fat diet in this study. Male Wistar rats were administered carbon tetrachloride for 5 weeks. At 12 weeks of age, one group was sacrificed. The remaining rats were divided into four groups according to whether or not they were administered carbon tetrachloride for 5 weeks, and whether they were fed a high-fat diet or control diet. At 12 weeks of age, liver fibrosis became apparent and then improved in the groups where carbon tetrachloride was discontinued, while it worsened in the groups where carbon tetrachloride was continued. Liver fibrosis was notable in both the carbon tetrachloride discontinuation and continuation groups due to the administration of a high-fat diet. In addition, liver precancerous lesions were observed in all groups, and tumor size and multiplicity were higher in the high-fat diet-fed groups. The expression of genes related to inflammation and lipogenesis were upregulated in rats fed a high-fat diet compared to their controls. The results suggest that a high-fat diet worsens liver fibrosis and promotes liver carcinogenesis, presumably through enhanced inflammation and lipogenesis, even after eliminating the underlying cause of liver cirrhosis.

Yes-associated protein inhibition ameliorates carbon tetrachloride-induced acute liver injury in mice by reducing VDR.

Carbon tetrachloride (CCl4) has a wide range of toxic effects, especially causing acute liver injury (ALI), in which rapid compensation for hepatocyte loss ensures liver survival, but proliferation of surviving hepatocytes (known as endoreplication) may imply impaired residual function. Yes-associated protein (YAP) drives hepatocytes to undergo endoreplication and ploidy, the underlying mechanisms of which remain a mystery. In the present study, we uncover during CCl4-mediated ALI accompanied by increased hepatocytes proliferation and YAP activation. Notably, bioinformatics analyses elucidate that hepatic-specific deletion of YAP substantially ameliorated CCl4-induced hepatic proliferation, effectively decreased the vitamin D receptor (VDR) expression. Additionally, a mouse model of acute liver injury substantiated that inhibition of YAP could suppress hepatocytes proliferation via VDR. Furthermore, we also disclosed that the VDR agonist nullifies CCl4-induced ALI alleviated by the YAP inhibitor in vivo. Importantly, hepatocytes were isolated from mice, and it was spotlighted that the anti-proliferative impact of the YAP inhibitor was abolished by the activation of VDR within these hepatocytes. Similarly, primary hepatic stellate cells (HSCs) were isolated and it was manifested that YAP inhibitor suppressed HSC activation via VDR during acute liver injury. Our findings further elucidate the YAP's role in ALI and may provide new avenues for protection against CCl4-drived acute liver injury.

Ameliorative effects of sildenafil against carbon tetrachloride induced hepatic fibrosis in rat model through downregulation of osteopontin gene expression.

The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body's storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil's hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl4). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl4 by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1ß, osteopontin (OPN), and transforming growth factor-ß (TGF-ß)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl4 through suppressing OPN.

Resveratrol treatment ameliorates hepatic damage via the TGF-ß/SMAD signaling pathway in a phenobarbital/CCl4-induced hepatic fibrosis model.

Objectives: Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-ß/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl4 induced hepatic fibrosis rat model. Materials and Methods: This model was created through phenobarbital and CCl4 (0.2-0.35 ml/kg). Resveratrol (1 mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-ß1, and PCNA in liver tissue. The TUNEL method and Masson's Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD2, SMAD3, SMAD4, and SMAD7 expression levels were measured to determine TGF-ß1 related hepatic fibrosis. Results: The SMAD2, SMAD3, and SMAD4 mRNA expression levels were increased and the SMAD7 mRNA expression level was decreased in the fibrosis control group. The SMAD7 mRNA expression level was higher in the phenobarbital-CCl4 induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-ß1/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells. Conclusion: Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl4 induced hepatic fibrosis.

Effectiveness of human adipose tissue-derived mesenchymal stem cells expressing alpha-1 antitrypsin gene in liver fibrosis: a study in mice.

Aim: The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis. Background: For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system. Methods: Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice's tail vein. Fourteen days' post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) staining. Results: Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT. Conclusion: These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.

Low Energy (<10†eV) Electron Collision with Benzonitrile-CCl4 Admixture: A Combined Theoretical and Experimental Study.

Benzonitrile (BZN) and carbon tetrachloride (CCl4) are versatile solvents used as a precursor for the synthesis of many products. As multi-usage molecules, these compounds may be involved in sustainable chemistry processes such as the cold plasma techniques for which the generated electrons are known to be responsible for reactions. Therefore, it is desirable to explore the interaction of low energy electrons with the co-compounds in the gas phase. The production of chlorine and cyanine anions, initiated by the electron collision with CCl4 and BZN, respectively, undergo nucleophilic substitution SN2 reaction with the precursors molecules for the synthesis of chlorobenzene and tricholoacetonitrile. The mechanism of fragmentation of benzonitrile and the synthesis reactions are rationalized by DFT calculations. The yield of the cyanine anion produced from the ion reaction increases with the temperature of the admixture gas, probed in the 25-100 °C temperature range. The present work may contribute to a potential process for the production of chlorobenzene for instance via (cold) plasma techniques.

Half-Inch Monolithic Spatial Heterodyne Raman Spectrometer: A Study of Polarized Raman Spectra of Organic Liquids and Instrumental Performance.

Raman spectroscopy allows for the unambiguous identification of materials through the inelastic scattering of light. This technique has a great many uses in various aspects of society from academic, scientific, and industry. This paper explores a specific type of Raman spectrometer called a spatial heterodyne Raman spectrometer (SHRSy), which is a variation of an interferometric spectrometer. It utilizes a Michelson interferometer and replaces the mirrors with gratings that transform it from a time-domain spectrometer to a spatial-domain spectrometer, allowing for the entirety of the spectrum to be captured at once. This study specifically tests a half-inch two-grating monolithic SHRS (½-in. 2g-mSHRS), which has a weight of <60 g and a size of 2.2 × 2.2 × 1.3 cm. To do this we excite a variety of organic liquids with a 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) pulsed laser, using an excitation energy of 6.5 mJ/pulse and distance of 3 m in conjunction with an intensified charge-coupled device camera. This is the first time that the SHRS has been used for investigating polarized Raman spectra of liquids. We discuss and contrast the instrumental properties such as resolution, spectral range, étendue, and field of view with previously tested mSHRS to give context to the instrument's performance.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism. METHODS: First, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4-10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity. CONCLUSIONS: A new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling.

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-Ò¡B, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis.

Background: The occurrence and development of Hepatic fibrosis (HF) are closely related to the gut microbial composition and alterations in host metabolism. Qijia Rougan decoction (QJ) is a traditional Chinese medicine compound utilized clinically for the treatment of HF with remarkable clinical efficacy. However, its effect on the gut microbiota and metabolite alterations is unknown. Therefore, our objective was to examine the impact of QJ on the gut microbiota and metabolism in Carbon tetrachloride (CCl4)-induced HF. Methods: 40% CCl4 was used to induce HF, followed by QJ administration for 6 weeks. Serum biochemical analyses, histopathology, immunohistochemistry, RT-PCR, 16S rRNA gene sequencing, and non-targeted metabolomics techniques were employed in this study to investigate the interventional effects of QJ on a CCl4-induced HF model in rats. Results: This study demonstrated that QJ could effectively ameliorate CCl4-induced hepatic inflammation and fibrosis. Moreover, QJ upregulated the expression of intestinal tight junction proteins (TJPs) and notably altered the abundance of some gut microbes, for example, 10 genera closely associated with HF-related indicators and TJPs. In addition, metabolomics found 37 key metabolites responded to QJ treatment and strongly associated with HF-related indices and TJPs. Furthermore, a tight relation between 10 genera and 37 metabolites was found post correlation analysis. Among them, Turicibacter, Faecalibaculum, Prevotellaceae UCG 001, and unclassified Peptococcaceae may serve as the core gut microbes of QJ that inhibit HF. Conclusion: These results suggest that QJ ameliorates hepatic inflammation and fibrosis, which may be achieved by improving intestinal tight junctions and modulating gut microbiota composition as well as modulating host metabolism.

Enhanced Fe(OH)2-driven reductive Dechlorination via shortened Fe-O bonds and colloidal medium.

Fe2+ is usually adsorbed to the surface of iron-bearing clay, and iron (hydr)oxide in groundwater. However, the reductive activity of Fe(OH)2, a prevalent intermediate during the transformation of Fe2+, remains unclear. In this study, high-purity Fe(OH)2 was synthesized and tested for its activity in the degradation of carbon tetrachloride (CT). XRD data confirm that the synthesized material is a pure Fe(OH)2 crystal, exhibiting sharp peaks of (001) and (100) facets. Zeta potential analysis confirms that the off-white Fe(OH)2 is a colloidal suspension with a positive charge of ∼+35-50 mV. FTIR spectra reveal the formation of a coordination compound Fe2+ with OH-/OD-, derived from NaOH/OD. SEM and HRTEM results demonstrate that the Fe(OH)2 crystal has a regular octahedral structure with a size of ∼30-70 nm and average lattice spacings of 2.58 Å. Mössbauer spectrum verifies that the Fe2+ in Fe(OH)2/Fe(OD)2 is hexacoordinated with six Fe-O bonds. XAFS data demonstrate that the Fe-O bonds become shorter as the OH-:Fe(II) ratios increase. DFT results indicate that the (100) crystal face of Fe(OH)2 more readily transfers electrons to CT. In addition to being adsorbed to iron compounds, structural Fe2+ compounds such as Fe(OH)2 could also accelerate the electron transfer from Fe2+ to CT through shortened Fe-O bonds. The rate constant of CT reduction by Fe(OH)2 is as high as 0.794 min-1 when the OH-:Fe(II) ratio is 2.5 in water. This study aims to enhance our understanding of the structure-reactivity relationship of Fe2+ compounds in groundwater, particularly in relation to electron transfer mechanisms.