SD Rat Liver Research Articles

Prenatal exposure to bisphenol AF causes toxicities in liver, spleen, and kidney tissues of SD rats

As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.

Tannic acid coating gauze immobilized with thrombin with ultra-high coagulation activity and antimicrobial property for uncontrollable hemorrhage

Rapid and safe hemostasis is crucial for the survival of bleeding patients in prehospital care. It is urgent to develop high performance hemostatic material to control the massive hemorrhage in the military field and accidental trauma. In this work, an efficient protein hemostat of thrombin was immobilized onto commercial gauze, which was mediated by self-polymerization and anchoring of tannic acid (TA). Through TA treatment, the efficient immobilization of thrombin was achieved, preserving both the biological activity of thrombin and the physical properties of the dressing, including absorbency, breathability, and mechanical performance. Moreover, in the presence of TA coating and thrombin, Gau@TA/Thr could obviously shortened clotting time and enriched blood components such as plasma proteins, platelets, and red blood cells, thereby exhibiting an enhanced in vitro coagulation effect. In SD rat liver volume defect and artery transection hemorrhage models, Gau@TA/Thr still had outstanding hemostatic performance. Besides, the Gau@TA/Thr gauze had inherent antibacterial property and demonstrated excellent biocompatibility. All results suggested that Gau@TA/Thr would be a potential candidate for treating uncontrollable hemorrhage in prehospital care.

Additive-free Absorbable Keratin Sponge With Procoagulant Activity for Noncompressible Hemostasis.

The development of a natural, additive-free, absorbable sponge with procoagulant activity for noncompressible hemostasis remains a challenging task. In this study, we extracted high molecular weight keratin (HK) from human hair and transformed it into a hemostatic sponge with a well-interconnected pore structure using a foaming technique, freeze-drying, and oxidation cross-linking. By controlling the cross-linking degree, the resulting sponge demonstrated excellent liquid absorption ability, shape recovery characteristics, and robust mechanical properties. The HK10 sponge exhibited rapid liquid absorption, expanding up to 600% within 5 s. Moreover, the HK sponge showed superior platelet activation and blood cell adhesion capabilities. In SD rat liver defect models, the sponges demonstrated excellent hemostatic performance by sealing the wound and expediting coagulation, reducing the hemostatic time from 825 to 297 s. Furthermore, HK sponges have excellent biosafety, positioning them as a promising absorbable sponge with the potential for the treatment of noncompressible hemostasis.

Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats

Previous studies have shown that trans fatty acids (TFA) are associated with several chronic diseases, the gut microbiota is directly influenced by dietary components and linked to chronic diseases. Our research investigated the effects of elaidic acid (EA), a typical TFA, on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases. 16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks. The results showed that the intake of EA increased the abundance of well-documented harmful bacteria, such as Proteobacteria, Anaerotruncus, Oscillibacter and Desulfovibrionaceae. Plus, EA induced translocation of lipopolysaccharides (LPS) and the above pathogenic bacteria, disrupted the intestinal barrier, led to gut-liver axis derangement and TLR4 pathway activation in the liver. Overall, EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats, leading to the activation of NLRP3 inflammasome and inflammatory liver damage.

Polysaccharides from Dendrobium officinale improve obesity-induced insulin resistance through the gut microbiota and the SOCS3-mediated insulin receptor substrate-1 signaling pathway.

Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation. The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors. Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.

Polydopamine functionalized polyurethane shape memory sponge with controllable expansion performance triggered by near-infrared light for incompressible hemorrhage control

Uncontrolled expansion of shape memory sponges face a significant challenge in the treatment of lethal incompressible hemorrhage, which can lead to blood overflow or damage to the surrounding tissue. Herein, we developed a polydopamine functionalized polyurethane shape memory sponge (PDA-TPI-PU) with a controllable degree of expansion by near-infrared (NIR) light-triggered stimulation for the treatment of incompressible hemorrhage. The sponge has excellent liquid absorption performance and robust mechanical strength as well as good photothermal conversion ability. Under NIR light of 0.32 W/cm2, the maximum recovery rate of the fixed-shape compression sponge was 91% within 25 s in air and 80% within 25 s in blood. In the SD rat liver penetrating injury model, compared with commercial medical gelatin sponge and PVA sponge, the PDA-TPI-PU sponge could effectively control the bleeding under the NIR light irradiation and did not cause excessive compression of the wound. The sponge with these characteristics shows potential application prospects as a hemostatic material.

Filamin A facilitates NLRP3 inflammasome activation during arsenic-induced nonalcoholic steatohepatitis.

Prolonged exposure to arsenic can cause nonalcoholic steatohepatitis (NASH). The NOD-like receptor protein 3 (NLRP3) inflammasome plays an essential role in the process of NASH. However, the mechanism by which arsenic promotes NLRP3 expression remains unclear. Three-month NaAsO2 gavage led to the nuclear factor-κB (NF-κB) signaling pathway activation and NASH. Additionally, NaAsO2 upregulated the level of Filamin A (FLNA) and pyroptosis, thereby activating the NLRP3 inflammasome in SD rat liver. Using FLNA siRNA, NASH-associated inflammation and pyroptosis were clearly mitigated by reducing activation of the NLRP3 inflammasome. Furthermore, arsenic treatment facilitated activation of the NF-κB signaling pathway and promoted p-p65 translocation into the nucleus. Chromatin immunoprecipitation (Ch-IP) assay indicated that FLNA promoted p65 binding to the NLRP3 gene and upregulated the transcription of NLRP3, ultimately leading to pyroptosis and NASH. Our findings indicate that FLNA and pyroptosis are strongly associated with NASH induced by NaAsO2. Collectively, the findings of this study indicated that FLNA mediates NF-κB signaling pathway-induced activation of the NLRP3 inflammasome and ultimately activates pyroptosis and NASH upon NaAsO2 exposure. This information may be useful for improving therapeutic strategies against arsenic-induced NASH.

1569-P: Lysophosphatidic Acid Mediates Inflammation in Liver and White Adipose Tissue in a Rat Model of 1-acyl-sn-glycerol-3-phosphate Acyltransferase 2 Deficiency

AGPAT2 (1-acyl-sn-glycerol-3-phosphate acyltransferase 2) converts lysophosphatidic acid (LPA) into phosphatidic acid (PA) and mutations of the AGPAT2 gene are responsible for the most common form of congenital generalized lipodystrophy (CGL) which leads to diabetes and steatohepatitis. The underlying mechanism by which AGPAT2 deficiency leads to these abnormalities has not been elucidated. We explored this question using an antisense oligonucleotide (ASO) to knock down expression of AGPAT2 in liver and white adipose tissue (WAT) of adult male SD rats. AGPAT2 ASO treatment induced lipodystrophic features in which adipose and hepatic inflammation were associated with increased LPA content in WAT (Control ASO=0.4 ± 0.1 nmol/g tissue; AGPAT2 ASO=0.8 ± 0.4, P<0.05) and liver (Control ASO=2.7 ± 0.4 nmol/g tissue; AGPAT2 ASO=4.2 ± 0.9, P<0.01) whereas PA content was unchanged. We hypothesized that increased LPA content may lead to inflammation in these tissues. We tested if either a controlled-release mitochondrial protonophore (CRMP) or an ASO against glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) would reduce LPA content and inflammation in these tissues in AGPAT2 ASO treated rats. CRMP treatment (20 mg/[kg-day]) primarily prevented LPA accumulation in WAT (Control ASO=0.4 ± 0.1 nmol/g tissue; AGPAT2 ASO=0.9 ± 0.1; AGPAT2 ASO+CRMP=0.6 ± 0.1) (AGPAT2 ASO vs AGPAT2+CRMP P<0.05) and prevented WAT inflammation. In contrast GPAM ASO treatment primarily prevented hepatic LPA accumulation (Control ASO=3.6 ± 0.4 nmol/g tissue; AGPAT2 ASO=4.8 ± 0.2; AGPAT2+GPAM ASO=2.7 ± 0.4) (AGPAT2 ASO vs AGPAT2+GPAM ASO P<0.01) and prevented hepatic inflammation. Conclusion: These results demonstrate a key role of LPA acid in mediating inflammation in liver and WAT in AGPAT2 deficient animals and identify novel therapeutic targets to treat CGL in patients with AGPAT2 deficiency. Disclosure I.Sakuma: None. R.C.Gaspar: None. P.Luukkonen: None. M.Kahn: None. S.Murray: Employee; Ionis Pharmaceuticals. V.Samuel: None. K.Petersen: Advisory Panel; Novo Nordisk, Research Support; Merck Sharp & Dohme Corp., Gilead Sciences, Inc. G.I.Shulman: Consultant; Novo Nordisk, DiCerna Pharmaceuticals, Inc., Bayer Consumer Care AG, Kriya Therapeutics, Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Other Relationship; AstraZeneca, Merck & Co., Inc., Janssen Research & Development, LLC, iMetabolic Biopharma Corporation, Maze Therapeutics, 89bio, Inc., Equator Therapeutics, Inc., Generian Pharmaceuticals, Fortress Biotech, Inc., OrsoBio, Aro Biotherapeutics Company, Stock/Shareholder; Levels Health, Inc.

Triphenyltin (TPT) exposure causes SD rat liver injury via lipid metabolism disorder and ER stress revealed by transcriptome analysis

BackgroundTPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear. ObjectiveTo explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs. MethodsMale SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 10 days of continuous gavage, HE staining was used to observe the morphological structure of liver tissue, serum biochemical indicators were detected, gene expression and functional enrichment analysis were performed by RNA-seq, Western Blot was used to detect the protein expression level of liver tissue, and qRT-PCR was used to detect the gene expression. ResultsAfter TPT exposure, the liver structure damaged; serum TBIL, AST and m-AST levels were significantly increased in the TPT-M group, and serum TG levels were significantly decreased in the TPT-H group. TCHO and TG in liver tissues were significantly increased; transcriptomic analysis detected 105 differential genes. Enrichment analysis showed that TPT exposure mainly affected fatty acid metabolism and drug metabolism in liver tissue, and also affected the redox process of liver tissue; the protein expression levels of PPARα, PPARγ, AMPK, RXRα, IRE1α and PERK were significantly increased after TPT exposure; the expression levels of lipid metabolism-related genes Acsl1, Elovl5, Hmgcr, Hmgcs1 and Srebf1 were significantly increased in the TPT-L group, while in the TPT-M and TPT-H groups had no significant change. ConclusionsTPT exposure can cause liver injury, lipid metabolism disorder and ER stress.

Gelatin Methacryloyl-Based Sponge with Designed Conical Microchannels for Rapidly Controlling Hemorrhage and Theoretical Verification.

It remains a challenge to develop effective hemostatic products in battlefield rescue for noncompressible massive hemorrhage. Some previous research had concentrated on the modification of different materials to improve the hemostasis ability of sponges. Herein, to investigate the relationship between the taper of microchannels and hemostatic performance of porous sponges, gelatin methacryloyl-based sponges with designed conical microchannels and a disordered porous structure were prepared using the 3D printing method and freeze-drying technology. Experiments and theoretical model analysis demonstrated that the taper and distribution of microchannels in the sponge affected the water and blood absorption properties, as well as the expansion ability. In treatment of SD rat liver defect and SD rat liver perforation wound, GS-1 sponge with the taper (1/15) microchannels exhibited an excellent hemostatic effect with blood loss of 0.866 ± 0.093 g and a hemostasis time of 280 ± 10 s. Results showed that the hemostatic capacities of GelMA sponges were increased with the bottom diameter (taper) of conical microchannels. This is a potential strategy to develop designed taper sponges with designed taper microchannels for rapidly controlling hemorrhage.

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.

Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

Fabrication, in vitro and in vivo properties of porous Zn–Cu alloy scaffolds for bone tissue engineering

Zn-based porous scaffolds have attracted increasing attention in the field of bone tissue engineering. In this study, the air pressure infiltration method (APIM) was employed to prepare porous Zn-xCu (x = 0, 1, 2, and 3 wt%) scaffolds. The porous structure, microstructure, mechanical properties, corrosion behavior, antibacterial properties and cytotoxicity of these porous scaffolds were systemically investigated. The pure Zn and the Zn–2Cu porous scaffolds were selected for the animal experiment to evaluate feasibility as orthopedic implant material using micro-computed tomography, histological analysis, and blood biochemical indicators. Uniformly distributed pores with an average size of 275 μm were confirmed in the Zn–Cu scaffolds. The plateau stress σy of the Zn–Cu scaffolds at 3% deformation was 2.55–51.15 MPa, and the elastic modulus E was 0.34–3.75 GPa. Hence, the mechanical properties of these scaffolds were similar to those of human cancellous bone. Porous Zn-xCu scaffolds exhibited a uniform corrosion morphology in simulated body fluid solution, and the addition of Cu facilitated the corrosion progress of the scaffold. Porous Zn-xCu scaffolds exhibited an effective antibacterial property against S. aureus and E.coli. The antibacterial activity increased with the increasing Cu contents. The porous Zn-xCu scaffolds exhibited good cytocompatibility at a low extract's concentration (25%), and the Zn–Cu scaffold exhibited a better cytocompatibility to MC3T3 pre-osteoblast cells than L-929 cells. Both pure zinc and Zn–2Cu porous scaffolds showed good biocompatibility in vivo. The blood biochemical parameters of SD rats within six months after operation were all within the acceptable range, and the implants had no side effect on the liver and kidney functions of SD rats.

Exploration of animal models to study the life cycle of Fasciola hepatica.

The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.

Polyvinyl alcohol/sodium alginate composite sponge with 3D ordered/disordered porous structure for rapidly controlling noncompressible hemorrhage

It is still a challenge to develop a sponge that can efficiently control noncompressible bleeding to meet the emergency treatment and clinical demand. Herein, we combined the 3D printing sacrificial template method and freeze-drying technology to prepare polyvinyl alcohol/sodium alginate (PVA/SA) composite sponges with ordered microchannels and disordered porous structure. Compared with conventional sponges, the prepared sponge showed ultra-rapid water/blood absorption capacity and satisfactory mechanical properties. Furthermore, when the sponge was stuffed into a noncompressible wound and contacted with blood, it could accurately guide and quickly absorb a large amount of blood through the microchannels. Moreover, the platelets, red blood cells and coagulation factors would be enriched in the microchannels and microporous structure.In the SD rat liver noncompressible hemorrhage and femoral artery puncture injury model, PVA-SA composite sponge with 3D ordered/disordered porous structure showed enhanced hemostatic performance compared with commercial MPVA sponges. Depend on the special ordered/disordered porous structure, PVA-SA composite sponge could accelerate the blood convergence and promote coagulation. This design of special porous structure opened up a new avenue to develop hemostatic sponges for rapidly controlling noncompressible hemorrhage.

MiR-27a-5p regulates acrylamide-induced mitochondrial dysfunction and intrinsic apoptosis via targeting Btf3 in rats

Acrylamide (AA), a potential carcinogen, is commonly formed in foods rich in carbohydrates at high heat. It is known that AA-induced mitochondrial dysfunction is responsible for its toxicity. Previously we found AA exposure increased miR-27a-5p expression in livers of SD rats. Here, the regulation mechanism of miR-27a-5p in mitochondrial dysfunction was investigated in rat liver cell lines (IAR20) and SD rats. The results showed that the overexpressed miR-27a-5p contributes to modulating mitochondrial dysfunction and Btf3 is identified as its target gene. The knockdown of Btf3 increases the cleaved PARP1 level and the phosphorylation of ATM and p53, which results in mitochondria-dependent apoptosis. Therefore, the miR-27a-5p-Btf3-ATM-p53 axis might play a vital role in the promotion of AA-induced cell apoptosis through disrupting mitochondrial structure and function. This would provide a potential target for the assessment and intervention of AA toxicity.

Inhibitory ability of Lactobacillus fermentum CQPC10 on lead toxicity induced by lead acetate in rats

This study studied the adsorption of Lactobacillus fermentum CQPC10 (LF-CQPC10) to induce lead acetate. The animal experiments showed that LF-CQPC10 reduced SD rat serum, liver, kidney and brain lead and maintained the cellular structure and state of liver and kidney tissues. Furthermore, LF-CQPC10 could improve anti-inflammatory cytokinine by reducing anti-inflammatory cytokinine IL-1β, IL-6, TNF-α and IFN-γ and raising IL-10. At the same time, LF-CQPC10 can also enhance the δ-ALAD enzyme activity and decrease the enzyme activities of ATL and AST, and decrease the contents of serum BUN and CRE of rats with lead toxicity injury. Compared with EDTA, LF-CQPC10 not only has better lead ion degradation ability, but also has better anti-inflammatory and organ protection effects. As a lactic acid bacteria, which can be used in food industry, LF-CQPC10 reduce the lead content and lead toxicity in food.

Effect of amoxicillin on the enamel mineralization of SD rats

Objective: To determine whether amoxicillin had an effect on the enamel mineralization of SD rats. Methods: Eighteen SD rats were randomly divided into three groups. The rats in the control group were given distilled water. The rats in two experimental groups were administered 50 or 100 mg/kg amoxicillin by intragastric administration from day 3 to day 17 after birth. The general condition, the structure of liver and kidney, the enamel surface changes of mandibular first molars and incisors were observed. The changes of Ca/P ratio on enamel surface were analyzed by X-ray energy dispersive spectrometer (EDS). The surface morphology after phosphoric acid treatment was examined by scanning electron microscopy (SEM). Histological changes in the ameloblasts of mandibular incisors were analyzed by hematoxylin and eosin (HE) staining. Results: Compared with the control group, the general conditions as well as liver and kidney structures of SD rats in 50 and 100 mg amoxicillin groups had no significant differences. There was no obvious chalky changes on the first mandibular molars of SD rats in each group. All the incisors in 50 and 100 mg groups showed different degrees of chalkiness in the labial incisal 1/3 enamel. X-ray EDS analysis showed that the Ca/P ratios of occlusal and incisal 1/3 enamel in 50 and 100 mg groups (occlusal 1/3 of mandibular first molars: 1.51±0.03 and 1.52±0.02, incisal 1/3 of mandibular incisors: 1.46±0.01 and 1.43±0.01) was significantly lower than that in the control group (occlusal 1/3 of mandibular first molars: 1.67±0.41, incisal1/3 of mandibular incisors: 1.73±0.07) (P<0.05). However, there was no significant differences in the cervical 1/3 Ca/P ratio of mandibular first molars and incisors among the three groups (mandibular first molars: 1.56±0.04 for control group, 1.59±0.05 for 50 mg group and 1.57±0.04 for 100 mg group; incisors: 1.52±0.02 for control group, 1.47±0.01 for 50 mg group and 1.51±0.03 for 100 mg group) (P>0.05). SEM observation showed that the enamel rods of the first molars and incisors in the 50 and 100 mg group varied in size and arranged disorderly. The spaces between the enamel rods were larger than that in the control group and some areas even appeared large pits. HE staining showed that the gaps between ameloblasts in 50 and 100 mg groups were significantly wider than that in the control group. Conclusions: Intake of amoxicillin during the period of enamel development of SD rats might affect enamel mineralization.

Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics

Ethnopharmacological relevance25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity.Aim of the study: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. Materials and methodsThe rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. ResultsThe results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. ConclusionConsidering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Histoarchitectural Changes in the Liver Following Lactational Lead Intoxication in Sprague Dawley Rats

The present experiment was designed to study the histoarchitectural changes in the liver following lactational lead (Pb) intoxication in rats. A total of 12 adult female and 4 male rats were used in the experiment and 32 offspring for the analysis of lactational lead intoxication. The offspring were divided into four groups. Groups B, C and D were administered 10 mg/dL, 30 mg/dL and 70 mg/dL of lead acetate respectively, via drinking water for 21 days through the lactating mothers while group A was control. The livers of the pups were observed using histological methods. One-way ANOVA was used to analyze data, followed by Tukey post hoc test for multiple comparisons. The results from the analysis showed that the total body weight, body length and liver weights were only slightly altered in the Pb intoxicated groups. Using relative liver weights alone revealed some form of hepatomegaly among the experimental groups. The results revealed a dose-dependent increase in blood lead concentration. Histopathological evidences revealed moderate to severe histoarchitectural distortions along Pb concentration gradient. Lactational lead intoxication portends dose dependent histopathological changes in the liver of SD rats.

Arsenic induces hepatic insulin resistance via mtROS-NLRP3 inflammasome pathway

Hepatic insulin resistance (IR) is the key event for arsenic-caused type 2 diabetes (T2D). However, the unequivocal mechanism of arsenic-induced hepatic IR remains unclear. The current study determined the role of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in arsenic-induced IR and revealed the underlying mechanism. Three-month NaAsO2 gavage led to glucose intolerance and insulin insensitivity, impaired hepatic insulin signaling. Additionally, NaAsO2 upregulated the level of oxidized mitochondrial DNA (ox-mtDNA) and mitophagy, thereby activating the NLRP3 inflammasome in SD rat liver. In vitro, we demonstrated that NaAsO2-induced IR depended upon the NLRP3 inflammasome activation. Moreover, inhibiting mitophagy mitigated the NLRP3 inflammasome activation and impaired insulin signaling induced by NaAsO2. Furthermore, mitochondrial reactive oxygen species (mtROS) scavenger alleviated the upregulated ox-mtDNA and mitophagy, thereby inhibiting the NLRP3 inflammasome activation, and improving insulin signaling. Taken together, these data demonstrated that mtROS-triggered ox-mtDNA, mitophagy, and the activation of NLRP3 inflammasome was involved in arsenic-induced hepatic IR.