Serum AST Levels Research Articles

Anti-hyperuricemic effects of the seeds of Hovenia acerba in hyperuricemia mice

Ethnopharmacological relevanceThe seeds of Hovenia acerba water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA). Aim of the studyTo evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms. Materials and methodsThe anti-HUA effects were evaluated on a mouse model by testing HAW’s effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways. ResultsHAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved. ConclusionHAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.

Protective effects of nutrients and antioxidant-rich seed oil and sprouted seed oil of Benincasa hispida against formaldehyde-induced hepatic and renal damage

IntroductionIn traditional Chinese medicine (TCM), Benincasa hispida, commonly referred to as wax gourd, winter melon, or ash gourd, has been used extensively for managing fever, urinary dysfunction, cough with viscous mucus, pulmonary and periappendicular abscesses, edema, spermatorrhea, gonorrhea, discharge pus, and expel dampness. In this study, we investigated the antioxidant, macro- and micronutrients as well as the protective effects of Benincasa hispida seed oil (BHSO) and sprouted seed oil (BHSSO) against formaldehyde (FA)-induced liver and kidney damage in mice. MethodsThe in vitro antioxidant activity was evaluated using the DPPH radical scavenging assay. Protein, fat, fiber, and total carbohydrate contents were assessed, and micronutrients were determined using flame atomic absorption spectrophotometry. BHSO, BHSSO, and Vitamin E (3485 mg/kg, 3485 mg/kg, and 30 mg/kg p.o., respectively) were administered once daily shortly after formaldehyde exposure (10 mg/kg, I.P.) to separate groups of Swiss albino male mice for a period of 26 days to investigate their protective effects against hepatic and renal damage. The normal control group was given access to sterile tap water and a balanced diet, whereas the disease control group was given only 10 mg/kg of formaldehyde intraperitoneally. Results and DiscussionSerum ALT, AST, and creatinine levels were significantly elevated after formaldehyde (FA) administration. Histopathological examinations of liver and kidney tissue revealed degenerative changes in both organs. However, mice pretreated with BHSO and BHSSO showed a significant reduction in FA-induced elevations of serum ALT, AST, and creatinine levels and retained normal liver and kidney tissue histology. BHSO and BHSSO exhibited the ability to scavenge free radicals, as shown in vitro antioxidant studies. Essential micronutrients like zinc (Zn), copper (Cu), calcium (Ca), and chromium (Cr) were also found in both oils. These micronutrients may prevent the inactivation of antioxidant enzymes, thereby increasing free radical scavenging and preserving oxidation and antioxidant equilibrium. Moreover, both oils were found to contain crude fat and carbohydrates that are essential in safeguarding against formaldehyde-induced hepatic and renal damage by offering structural and metabolic support to cells and preserving membrane integrity. ConclusionBenincasa hispida seed oil and sprouted seed oil have significant protective effects against formaldehyde-induced hepatic and renal damage and serve as a valuable source of antioxidants, as well as macro- and micronutrients.

Therapeutic Potential of Aloe vera and Aloe vera-Conjugated Silver Nanoparticles on Mice Exposed to Hexavalent Chromium.

Hexavalent chromium (Cr (VI)) is a hazardous heavy metal that induces hepatotoxicity and nephrotoxicity. Thus, this study was planned to explore the ameliorating capacity of Aloe vera leaf gel extract (AV) and their conjugated silver nanoparticles (AVNP) against Cr (VI) induced hepatotoxicity and renal toxicity. The organ indices, level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total protein, and creatinine in blood serum were measured. The histopathological and micrometric analysis of the hepatic and renal tissue sections were studied. The hepatosomatic index was raised significantly (0.098 ± 0.13g) in Cr treated group. The blood serum level of AST (484 ± 10.7 U/L), ALT (163 ± 5.5 U/L), ALP (336.7 ± 9.5 U/L), MDA (642.3 ± 28.3 U/L), and creatinine (4.0 ± 0.1mg/dL) were increased significantly, whereas total protein level was declined (2.8 ± 0.3g/dL) significantly in Cr exposed group. In the histopathological study, necrosis, disturbed hepatic cords, impaired glomeruli, and Bowman's capsule were noted. Micrometric data from the liver and kidney revealed a significant surge in the size of hepatocytes and their nuclei (1188.2 ± 467.7µ2 and 456.5 ± 205.6µ2) and CSA of glomeruli and Bowman's capsule (9051.8 ± 249.8µ2 and 11,835.5 ± 336.7µ2) in Cr (VI) exposed group, whereas the brush border (10.2 ± 4.0µ) size declined significantly. The administration of AV and AVNP reduced the oxidative stress induced by Cr (VI).

Comparative Effects of Crocin and Losartan on RAGE, TGF-β, TNF-α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes.

AGEs, via RAGE, increase the development of hyperglycemia-induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF-α and TGF-β gene expression in diabetic rats, as well as histological changes in liver tissue. Diabetes was induced in 40 male Wistar rats using Streptozotocin (50 mg/kg, IP). There were five groups of rats: diabetic and healthy groups, diabetic rats given crocin (50 mg/kg), losartan (25 mg/kg) and both (crocin + Los). Serum glucose, ALT and AST levels were measured 4 weeks later. qPCR was used to examine the TNF-α, TGF-β and RAGE gene expression in liver tissue. Crocin was found to be effective in lowering FBG in the diabetes group. The serum levels of ALT and AST decreased in all treated groups, but this decrease was significant in the crocin + Los group (p < 0.05). The relative expression of RAGE, TNF-α and TGF-β genes was significantly higher in the diabetes group compared to the healthy group. The expression of these genes decreased in groups treated with crocin and Losartan compared to the diabetes group. The highest reduction in RAGE and TGF-β gene expression was reported in those treated with crocin + Los. Histopathology results showed that the diabetes group had more bile ducts and necrosis than the healthy control group, which had no tissue changes. Hepatocyte degeneration, bile duct proliferation, inflammatory changes and hepatocyte necrosis were mild in the treated groups, but no hepatocyte necrosis was observed in the crocin + Los group. Crocin may be a feasible therapeutic agent for treating diabetes and its symptoms when combined with pharmaceutical medications. Human research is still needed to reach clear conclusions.

Bruceine A attenuates fibrogenesis and inflammation through NR2F2-regulated HMGB1 inflammatory signaling cascades in hepatic fibrosis

This investigation explored the hepatoprotective capabilities of Bruceine A (BA) and its underlying mechanisms in mitigating hepatic fibrosis. Hepatic stellate cells (HSCs) and mouse primary hepatocytes were treated with TGF-β and subsequently exposed to BA. To assess the effects of BA on the NR2F2-HMGB1 signaling cascade, these cells underwent transfection with an siRNA vector targeting NR2F2. The interaction between NR2F2 and the HMGB1 promoter was elucidated using a dual luciferase assay. In vivo, C57BL/6 mice were treated with thioacetamide (TAA) to induce liver damage, followed by administration of BA. The study found that BA moderated extracellular matrix (ECM) buildup, epithelial-mesenchymal transition (EMT), and inflammatory mediator levels, while concurrently reducing NR2F2 and HMGB1 expression in activated HSCs. Furthermore, BA lessened pyroptosis in hepatocytes, curtailing the inflammatory response. The absence of NR2F2 in HSCs or hepatocytes hindered BA's inhibitory effect on this pathway. It was demonstrated that NR2F2 binds directly to the HMGB1 promoter. Treatment with BA resulted in diminished serum levels of ALT and AST, mitigated damage in hepatic tissues, and decreased the ECM and neutrophil extracellular traps (NETs), thus protecting hepatocytes from fibrosis. Furthermore, BA suppressed the synthesis of inflammatory mediators such as NLRP3, caspase-1, and IL-1β by blocking the NR2F2-driven HMGB1 pathway, markedly reversing hepatic fibrosis. These observations highlight the efficacy of BA as a viable therapeutic candidate for hepatic fibrosis.

Study on the biosafety and targeting efficiency of Escherichia coli outer membrane vesicles in breast tumor.

To seek out the targeting of Escherichia coli outer membrane vesicles (E. coli OMVs) in breast tumor-bearing mice and their biosafety in healthy mice. Ultrafiltration in conjunction with ultracentrifugation was utilized to concentrate E. coli OMVs, and characterize them. Subcutaneous breast tumors were induced in BALB/c mice to serve as an experimental model, and the biodistribution of E. coli OMVs in both tumor-bearing and healthy mice was monitored using an in vivo fluorescence imaging system. Utilizing frozen sections, the infiltration of E. coli OMVs in tumor tissues was appraised at the 24-hour post-injection. Healthy BALB/c mice were randomly divided into control group and vesicles group. Following the intravenous injection of E. coli OMVs, monitoring encompassed variations in body weight, blood routine indices, serum levels of AST, ALT, and BUN, organ indices (heart, liver, spleen, lung, and kidney), along with tissue histopathology over a 14-day period. The spherical E. coli OMVs had a diameter of (155.8 ± 3.1) nm and exhibited the expression of outer membrane proteins OmpA and OmpC. Upon assessment, it was evident that the E. coli OMVs persisted in the tumor tissues even 24h post-injection. An evident decrease in the body weight of the vesicles group, distinct from the control group, was observed on the second day after injection (P < 0.001); in contrast, no considerable differences were noted at subsequent time points (P > 0.05). Following the injection, the vesicles group displayed notable reductions in WBC and PLT as relative to the control group (P < 0.0001) on the initial day, however, there were no noteworthy distinctions as opposed to the control group for other hematological indices; No notable variances in hematological indices between the two groups were observed on the seventh and fourteenth day (P > 0.05). Over the 14 days, no substantial differences were observed in the serum levels of BUN, AST, ALT, and organ indices within the vesicles group as opposed to the control group (P > 0.05). Furthermore, there were no obvious abnormal changes in tissue morphology. 0.5mg/kg of E. coli OMVs can safely and effectively target 4T1 breast tumor in mice.

Antioxidant and Anti-Inflammatory Effects of Opuntia Extracts on a Model of Diet-Induced Steatosis.

Oxidative stress and inflammation are widely recognised as factors that can initiate and facilitate the development of MAFLD. The aim of this study is to analyse the effect of low and high doses of Opuntia stricta var. dillenii peel extract (L-OD and H-OD, respectively) and Opuntia ficus-indica var. colorada pulp extract (L-OFI and H-OFI, respectively), which are rich in betalains and phenolic compounds, on oxidative stress, inflammation, DNA damage and apoptosis in rat livers with diet-induced steatosis. Steatotic diet led to increased final body and liver weight, serum transaminases, hepatic TG content, oxidative status and cell death. H-OFI treatment decreased serum AST levels, while L-OFI reduced hepatic TG accumulation. Oxidative stress was partially prevented with H-OD and H-OFI supplementation, and pro-inflammatory cytokines levels were especially improved with H-OFI treatment. Moreover, H-OFI appears to prevent DNA damage markers. Finally, H-OD and L-OFI supplementation down-regulated the apoptotic pathway. In conclusion, both H-OD and H-OFI supplementation were effective in regulating the progression to metabolic steatohepatitis, triggering different mechanisms of action.

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) &amp; TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

Effects of Kalimeris indica on alcohol-induced liver injury through storing Nrf2/HO-1 pathway and gut microbiota.

Kalimeris indica (L.) Sch. Bip., (K. indica) is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of K. indica has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions. The HPLC-MS method was used to reveal the chemical composition of K. indica extract. HepG2 cells were used to test the in vitro oxidative stress. C57BL/6 mice were used to construct the in vivo alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the in vivo protective effect of ML (50 and 200mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the in vivo oxidative stress. Immunohistochemical experiments were used to examine the in vivo Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota. 16 compounds were identified from K. indica extract. K. indica treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that K. indica (50 and 200mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, K. indica could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that K. indica showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while K. indica treatment could result in a significantly richer variety of microbial communities compared to the alcohol group. K. indica (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that K. indica has a potential in the treatment of alcohol-induced liver injury.

Acetylcorynoline alleviates acute liver injury via inhibiting TLR4/JNK/NF-ĸB pathway Based on RNA-seq and molecular docking in vivo and in vitro

Acute liver injury is characterized by massive inflammatory cell infiltration, destruction of liver structure and abnormalities in liver function. Acetylcorynoline (AC) is one of the main chemical components of Corydalis bungeana Turcz. which has been shown to have a protective effect against acute liver injury. However, Whether AC is protective against acute liver injury remains unclear. This study aimed to explore the protective mechanism of AC against acute liver injury from in vivo as well as experiments in vitro. In experimental in vivo studies, AC pretreatment reduced the serum levels of ALT and AST and inhibited the expression of inflammatory factors in the liver of LPS/D-GalN-induced mice and alcohol liver disease mice. RNA-sequencing and molecular docking were used to predict that AC exerts its anti-inflammatory effects through the Toll-like receptor signaling pathway. Using RT-qPCR and Western blotting to detect expression levels of key genes and nodal proteins of the Toll-like receptor signaling pathway, AC was found to inhibit the phosphorylation of nuclear factor-kappaB (NF-ĸB) and c-Jun amino-terminal kinase (JNK). This finding was validated in cellular experiments. In conclusion, AC exerts its anti-hepatic injury effect by suppressing inflammation through inhibition of the TLR4/JNK/NF-ĸB pathway.

Effects of Vitamin D Supplementation and a Cafeteria Diet on Various Parameters in the Next Generation of Rats with Metabolic Syndrome.

Metabolic Syndrome (MetS) is an increasingly widespread public health problem worldwide. MetS is associated with a cafeteria diet characterized by high fat and high simple carbohydrates. A cafeteria diet significantly affects serum glucose, creatine, urea, triglyceride, cholesterol and MetS parameters such as ALT, AST and ALP. Due to its epigenetic effects, vitamin D is important in controlling MetS parameters and minimizing MetS findings in subsequent generations. In this study, the effect of weekly 0.3 mL (1.000 IU/week) vitamin D intervention on MetS parameters was investigated in parental rats developing high-fructose MetS and their offspring. Offspring of MetS rats receiving and not receiving vitamin D supplementation were divided into four different groups and exposed to a cafeteria diet and vitamin D supplementation for eight weeks. It was shown that parental rats in the intervention group had lower serum urea, glucose, creatine, total cholesterol, ALP, AST and ALT levels (p < 0.05). Serum urea, glucose, creatine, ALT, AST, ALP, triglyceride, total cholesterol levels and body weights were lower and HDL levels were higher in the offspring (p < 0.05). However, initial serum ALT and AST values were higher in the offspring of MetS parent rats receiving vitamin D supplementation and in the offspring of rats not receiving supplementation than in the offspring of supplemented parents. In conclusion, it was found that vitamin D supplementation improved MetS parameters in parent rats, positively affected MetS parameters in offspring rats despite an inadequate diet, and positively affected some MetS parameters by affecting epigenetic pathways in offspring born to MetS mothers.

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Evaluation of the Safety and Efficacy of Curcumin-Synthesized Silver Nanoparticles in Rats Exposed to Chlorpyrifos During Puberty Development.

Silver nanoparticles (Ag-NPs) have garnered significant attention in recent years due to their therapeutic effects. Curcumin (CUR) has been utilized as a coating agent for synthesizing Ag-NPs, intended to act as a potential drug. This study was designed to evaluate the safety and efficacy of curcuminsynthesized silver nanoparticles on rats exposed to chlorpyrifos (CPF) during their pubertal development. Forty-two male Wistar rats, 23 days old, were selected and randomly divided into 7 groups (n=6) as follows: positive control, negative control, CPF (5 mg/kg), silver nanoparticles synthesized using curcumin at 40 μg/kg (CUR-Ag-NPs 40), CUR-Ag-NPs 80, CPF+ CUR-Ag-NPs 40, CPF+ CUR-AgNPs 80. All treatments were administered via gavage for 30 days. At the end of the study, rats were anesthetized using ketamine (50 mg/kg), and xylazine, (10 mg/kg) and blood was collected from the heart for serum analysis of liver enzymes, urea, and creatinine. Liver and kidney tissues were isolated for histopathological analysis. No significant differences were observed in serum levels of AST, ALT, and ALP enzymes as well as urea and creatinine levels among the different groups. Light microscopy observation revealed multifocal inflammatory mononuclear cell subsets in liver tissue associated with mild inflammatory mononuclear cell infiltration in the portal region in CPF, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40, and CPF+CUR-Ag- NPs 80 groups. Histological examination of kidney tissue showed degenerative changes in the tubular epithelium, congestion, and mild infiltration of mononuclear inflammatory cells in the renal interstitial tissue in the CPF group, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40 and CPF+CUR-Ag-NPs 80 groups. This study failed to establish the safety and efficacy of CUR-Ag-NP at 40 and 80 μg/kg in prepubertal rats exposed to CPF. However, further studies should be conducted to thoroughly characterize the efficacy of CUR-Ag-NP in developmental animal models.

Cholestatic insult triggers alcohol-associated hepatitis in mice.

Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in patients with AH and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH. To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a subtoxic dose of α-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. Liver injury was measured by biochemical and histological methods. RNAseq was performed to determine hepatic transcriptomic changes. The impact of inflammation was assessed using an anti-LY6G antibody to deplete the neutrophils and DNase I to degrade neutrophil extracellular traps. ANIT synergistically enhanced liver injury following a 4-week EtOH feeding with typical features of AH, including increased serum levels of ALT, AST, and total bile acids, cholestasis, necrosis, neutrophil infiltration, and accumulation of neutrophil extracellular traps. RNAseq revealed multiple genes uniquely altered in the livers of EtOH/ANIT-treated mice. Analysis of differentially expressed genes suggested an enrichment of genes related to inflammatory response. Anti-LY6G antibody or DNase I treatment significantly inhibited liver damage in EtOH/ANIT-treated mice. Our results support the hypothesis that cholestasis can be a critical contributor to the pathogenesis of AH. A combined treatment of EtOH and ANIT in mice presents biochemical, histological, and molecular features similar to those found in patients with AH, suggesting that this treatment scheme can be a useful model for studying Alcohol-associated Cholestasis and Hepatitis (AlChoHep).

Exploring In Vitro Antibiofilm Potential and In Vivo Toxicity Assessment of Gold Nanoparticles.

In this study, biogenically synthesized AuNPs were first characterized via UV visible spectroscopy, SEM, XRD, and FTIR followed by toxicity evaluation using mice model. UV-visible spectroscopy of biogenic AuNPs showed peaks at 540-549 nm, while FTIR spectrum showed various functional groups involving O-H, Amide I, Amide II, O-H, C-H groups, and so on. SEM showed the size variation from 30 to 60 nm. Antibacterial potential against pathogenic isolates showed bigger ZOI (31.0 mm) against Pseudomonas aeruginosa AuNPs. Antibiofilm activity showing up to 100% inhibition at 90 µg mL-1 concentration of AuNPs. Toxicity evaluation showed LD50 as 70 mg kg-1. Exposure to AuNPs caused significant changes in the levels of serum AST (p < 0.05) at 100-150 mg kg-1 of AuNPs exposure. Histopathology of male albino mice kidney and liver revealed that mice exposed to maximum concentration of AuNPs showed necrosis, cell distortion, and hepatocytes detachment. Present study showed that biologically synthesized AuNPs possess effective antimicrobial and biofilm inhibitory potential. AuNPs strong bactericidal effect even at lower concentration suggest that NPs could have excellent potential for combating pathogens. In conclusion, nanotechnology may revolutionize human life and medical industry by developing innovative drugs with the potential to treat diseases in shorter and noninvasive time period. Hence, in vitro biosafety and experimental observations followed by in vivo outcomes are crucial in shifting the novel therapeutics into medical practice thus leading further into their future development.

Rosehip (Rosa rugosa Thunb.) ethanol extract ameliorates liver fibrosis through upregulation of the PPAR signaling pathway

The objective of this study was to examine the effect of rosehip (Rosa rugosa Thunb.) ethanol extract (RRE) on liver fibrosis in mice and the underlying molecular mechanisms. RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. Histopathological analysis showed that RRE significantly ameliorated inflammation, necrosis, and apoptosis of hepatocytes and collagen deposition caused by CCl4. Further assays indicated that RRE significantly suppressed the production of MDA while markedly increasing the levels of SOD and GSH in the liver. The AST, ALT, IL-6, IL-1β, TNF-α, HA, LN, PCIII, and IVC levels in serum were decreased by RRE. Transcriptome analysis shows that RRE significantly upregulates the PPAR signaling pathway. The RT-q PCR results further confirmed the RRE up-regulating Pparγ, Rxrα, and Plin5 in the PPAR signaling pathway. The Western blot and immunohistochemical results indicate that RRE upregulated PPARγ, RXRα, and Perilipin 5 while downregulating α-SMA and COL1A1 expression. The results indicate that RRE can ameliorate liver fibrosis in mice by upregulating the PPAR signaling pathway.

Evaluation of the Effect of Gum Arabic on the Histological and Physiological Changes in the Liver of Albino Rats Exposed to Bisphenol A

We designed this work in order to study the protective effect of aqueous extract of gum arabic (GA) from oxidative damage induced by bisphenol A(BPA). This study was conducted on 35 male laboratory Albino rats of Sprague Dawley strain (165-210 grams) and divided into five groups. Each group included 7 rats. The experiment was performed at the animal house of Biology (College of Education for Pure Sciences). The experiment continued for 90 days under conditions Standard laboratory, as follows: The first group was the control; the second group had GA taken orally; the third group had BPA taken orally; the fourth group had GA taken first, followed by BPS, and the fifth group had BPA taken first, followed by GA. According to the above results clearly, Serum levels of AST, ALT and Lipid profile (Cholesterol, Triglyceride) indicated a highly significant increase in these parameters at group 3, While the fourth and fifth groups show significant reductions in AST, ALT, cholesterol, triglycerides, and MDA, also significant increases in GSH levels, While the histological changes in the third group were represented by the presence of a state of blood congestion with depletion of glycoprotein and degeneration of some cells, in addition to the presence of a state of necrosis of liver cells, while it was not observed severe histological changes when compared to third group in both fourth and fifth groups. In Short, the above results indicated that GA treatment for BPA-induced liver injury had Therapeutic effect through anti-free radical formation and functional role as free scavenger.

Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.

Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.

Desmodium styracifolium (Osb.) Merr. Extracts alleviate cholestatic liver disease by FXR pathway

Ethnopharmacological relevanceCholestatic liver disease (CLD) is a disease characterized by cholestasis. Farnesoid X receptor (FXR) is a nuclear receptor that maintains homeostasis in bile acid metabolism. Studies have shown that gut microbiota interfered with the FXR pathway. Modulation of FXR to inhibit cholestasis has become a key measure in the treatment of CLD. In traditional folk medicine, Desmodium styracifolium (Osb.) Merr. was used as a primary treatment for gallstones, gonorrhea, jaundice, cholecystitis and other diseases. Modern pharmacological studies had also found that the herb has anti-calculus, anti-inflammatory, antioxidant, diuretic and liver damage. Therefore, we speculated that Desmodium styracifolium (Osb.) Merr. extracts (DME) could alleviate CLD through the FXR pathway and might be associated with the gut microbiota. However, studies of DME alleviating CLD through the FXR pathway have not been reported. Aim of studyTo study the effect and mechanism of DME in relieving CLD through in vivo and in vitro experiments. Materials and methodsFirst, mice were administrated with alpha-naphthyl isothiocyanate (ANIT) to establish a CLD model in vivo. Meanwhile, HepG2 cells were induced by lithocholic acid (LCA) to establish the CLD model in vitro. To evaluate the therapeutic effect of DME on CLD mice, hematoxylin-eosin (HE) staining, and biochemical indicators were performed. The prototype of the blood components in mice serum was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 16S rDNA sequencing was used to analyze the gut microbiota. Finally, the protein and mRNA expression of the FXR pathway in mice liver tissues or HepG2 cells were detected by Western blot, qRT-PCR, or immunofluorescence. ResultsPathological testing and biochemical indexes showed that DME significantly reduced serum ALT, AST, ALP, TBIL, DBIL, TBA and liver TBA levels, and attenuated liver tissue injury, necrosis and jaundice in CLD mice. In addition, MetagenomeSeq analysis of gut microbiota showed that DME significantly up-regulated the abundance of Parvibacter, down-regulated the abundance of Paenalcaligenes, and regulated bile acid homeostasis. In terms of mRNA expression, DME significantly upregulated the mRNA levels of Nr1h4, Abcb11, Cyp7a1 and Slc10a1. Meanwhile, in terms of protein expression, DME significantly up-regulated the protein expression levels of FXR, BSEP, CYP7A1 and NTCP, which regulated bile acid homeostasis. Finally, the molecular docking results showed that the components of DME, such as Lumichrome, Daidzein and Folic acid, all had good binding ability with FXR, and the surface plasmon resonance (SPR) results also showed that both Lumichrome and Daidzein had a relatively high affinity with FXR. ConclusionDME alleviated CLD through the FXR pathway, and the mechanisms might be associated with the gut microbiota.

Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25mg/kg twice weekly for 6weeks), and found that both IMP (25mg/kg and 12.5mg/kg) and dexrazoxane 12.5mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25µg/mL relieved DOX (1μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.