Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc--GSH-GPX4 signaling pathway in ferroptosis response.

Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc--GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity.

Anthelmintic efficacy of nitazoxanide in dogs naturally infected with Toxocara canis.

Toxocara canis (T. canis) is a gastrointestinal nematode in dogs, and its larvae also infect humans, causing severe larval migratory disease. Anthelmintic drugs have become the primary means to combat T. canis. In this study, the efficacy of nitazoxanide (NTZ) was tested against all the internal stages of T. canis, including L3 larval stage in vitro experiments and gastrointestinal worm in vivo experiments. In the in vitro experiment, after treatment with NTZ at 7.81 and 62.5 µg/mL for 12 h, the larval mortality efficacy reached 90.0 and 100.0%, respectively. In the in vivo experiments, 100 mg/kg NTZ possessed good anthelmintic efficacy against T. canis, with an egg per gram (EPG) reduction of 99.19%, and 90.00% of dogs cleared with residual worms. These results were comparable to those of the positive control drug. The highest anthelmintic efficacy was observed in the group treated with 150 mg/kg NTZ. Based on faecal egg counts, the number of T. canis eggs decreased by 100.00%, and the percentage of dogs cleared with residual worms achieved 90.00% after 7 days of treatment in the 150-mg/kg NTZ treatment group. In general, NTZ showed great potential to be applied as an anthelmintic against T. canis.

Development, validation, and use of a monitoring method for fipronil and its metabolites in chicken eggs by QuEChERS with online-SPE-LC-Q/Orbitrap analysis.

RATIONALE: The residues of fipronil and its metabolites in chicken eggs pose a threat to human health, so regular monitoring is necessary. However, the pretreatments of the existing detection methods are complex and time-consuming. A simple and streamlined pretreatment method is needed to improve the detection efficiency. METHOD: A rapid, efficient, and facile approach employing the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with online solid-phase extraction liquid chromatography tandem Q Exactive Orbitrap high-resolution mass spectrometry (online-SPE-LC-HRMS) was established and evaluated for the determination of fipronil, fipronil-desulfinyl, fipronil-sulfone, and fipronil-sulfide in chicken eggs. An improved sample preparation technique combining QuEChERS and online-SPE was developed. Negative targeted ion fragmentation scanning and targeted-selected ion monitoring of HRMS were adopted to identify and quantify the target analytes. RESULTS: The proposed pretreatment method took a few steps in <13 min to achieve excellent recoveries and negligible interference. High selectivity was acquired with the adoption of Q/Orbitrap HRMS. The limit of quantification (LOQ) of the analytes was 2.5 µg kg-1 , meeting the detection requirements of the maximum residue level enacted by the Codex Alimentarius Commission, Japan, and the United States for the sum of fipronil and its metabolites. Extraction recoveries at three spiked concentration levels were within 84.56% to 93.84%, with relative standard deviation ≤5.87%. CONCLUSION: The established method is efficient and easy to operate and displays satisfactory LOQs, recoveries, accuracy, and precision. This approach serves as a reference method for monitoring eggs while providing potential solutions for fipronil determination in more complicated matrices.

Acute liver injury induced by carbon tetrachloride reversal by Gandankang aqueous extracts through nuclear factor erythroid 2-related factor 2 signaling pathway.

The aims of this study were to evaluated the effect and underlying mechanism of Gandankang (GDK) aqueous extract in alleviating the acute liver injury induced by carbon tetrachloride (CCl4) in vivo and in vitro. Mice were divided into 5 groups (n = 8) for acute (Groups: control, 0.3 % CCl4, BD (Bifendate), 1.17, 2.34 and 4.68 mg/kg GDK) liver injury study. 10 µL/g CCl4 with corn oil were injected interperitoneally (i.p) expect the control group. HepG2 cells were used in vitro study. The results showed GDK can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, GDK inhibited CCl4-induced liver fibrosis and blocked the NF-κB pathway to effectively inhibit the hepatic inflammatory response; and inhibited CCl4-induced oxidative stress by upregulating the Keap1/Nrf2 pathway-related proteins and promoting the synthesis of several antioxidants. Additionally, it inhibited ferroptosis in the liver by regulating the expression of ACSl4 and GPX4. GDK reduced lipid peroxide generation in vitro by downregulating the production of reactive oxygen species and Fe2+ aggregation, thereby inhibiting ferroptosis and alleviating CCl4-induced hepatocyte injury. In conclusion, we describe the potential complex mechanism underlying the effect of GDK against acute liver injury.

Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection.

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3' to 5' exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, and the dysregulation of immune function and inflammation in host cells. The p53 tumor suppressor molecule is a critical regulator of cell signaling pathways, cellular stress responses, DNA repair, and apoptosis. However, viruses can activate or inhibit p53 during viral infections to enhance viral replication and spread. Given its pivotal role in cell physiology, p53 represents a potential target for anti-coronavirus drugs. This review aims to summarize the relationship between p53 and coronaviruses from various perspectives, to shed light on potential targets for antiviral drug development and vaccine design.

Mori fructus aqueous extracts attenuate carbon tetrachloride-induced renal injury via the Nrf2 pathway and intestinal flora.

Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl4). The mice were randomly divided into control group, CCl4 model group (10% CCl4), CCl4 + low and high MFAEs groups (10% CCl4 + 100 mg/kg and 200 mg/kg MFAEs). We found that MFAEs decreased the kidney index of mice, restored the pathological changes of renal structure induced by CCl4, reduced cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (Kim-1) blood urea nitrogen and creatinine contents in serum, promoted the nuclear transportation of Nrf2 (nuclear factor erythroid derived 2 like 2), elevated the expression of HO-1 (heme oxygenase 1), GPX4 (glutathione peroxidase 4), SLC7A11 (solute carrier family 7 member 11), ZO-1 (zonula occludens-1) and Occludin, suppressed the expression of Keap1 (kelch-like ECH-associated protein 1), HMGB1 (High Mobility Group Protein 1), ACSL4 (acyl-CoA synthetase long chain family member 4) and TXNIP (thioredoxin interacting protein), upregulated the flora of Akkermansia, Anaerotruncus, Clostridium_sensu_stricto, Ihubacter, Alcaligenes, Dysosmobacter, and downregulated the flora of Clostridium_XlVa, Helicobacter, Paramuribaculum. Overlapped with Disbiome database, Clostridium_XlVa, Akkermansia and Anaerotruncus may be the potential genera treated with renal injury. It indicated that MFAEs could ameliorate kidney injury caused by CCl4 via Nrf2 signaling.

Triacetyl Resveratrol Inhibits PEDV by Inducing the Early Apoptosis In Vitro.

PEDV represents an ancient Coronavirus still causing huge economic losses to the porcine breeding industry. Resveratrol has excellent antiviral effects. Triacetyl resveratrol (TCRV), a novel natural derivative of resveratrol, has been recently discovered, and its pharmacological effects need to be explored further. This paper aims to explore the relationship between PEDV and TCRV, which offers a novel strategy in the research of antivirals. In our study, Vero cells and IPEC-J2 cells were used as an in vitro model. First, we proved that TCRV had an obvious anti-PEDV effect and a strong inhibitory effect at different time points. Then, we explored the mechanism of inhibition of PEDV infection by TCRV. Our results showed that TCRV could induce the early apoptosis of PEDV-infected cells, in contrast to PEDV-induced apoptosis. Moreover, we observed that TCRV could promote the expression and activation of apoptosis-related proteins and release mitochondrial cytochrome C into cytoplasm. Based on these results, we hypothesized that TCRV induced the early apoptosis of PEDV-infected cells and inhibited PEDV infection by activating the mitochondria-related caspase pathway. Furthermore, we used the inhibitors Z-DEVD-FMK and Pifithrin-α (PFT-α) to support our hypothesis. In conclusion, the TCRV-activated caspase pathway triggered early apoptosis of PEDV-infected cells, thereby inhibiting PEDV infections.

Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats.

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats' kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.

Antiviral effects of ergosterol peroxide in a pig model of porcine deltacoronavirus (PDCoV) infection involves modulation of apoptosis and tight junction in the small intestine.

Porcine deltacoronavirus (PDCoV) is a newly discovered swine enteropathogenic coronavirus with worldwide distribution. However, efficient strategies to prevent or treat the infection remain elusive. Our in vitro study revealed that ergosterol peroxide (EP) from the mushroom Cryptoporus volvatus has efficient anti-PDCoV properties. The aim of this study is to evaluate the potential of EP as a treatment for PDCoV in vivo and elucidate the possible mechanisms. Seven-day-old piglets were infected with PDCoV by oral administration in the presence or absence of EP. Piglets infected with PDCoV were most affected, whereas administration of EP reduced diarrhea incidence, alleviated intestinal lesion, and decreased viral load in feces and tissues. EP reduced PDCoV-induced apoptosis and enhanced tight junction protein expressions in the small intestine, maintaining the integrity of the intestinal barrier. EP showed immunomodulatory effect by suppressing PDCoV-induced pro-inflammatory cytokines and the activation of IκBα and NF-κB p65, and upregulating IFN-I expression. Knockdown of p38 inhibited PDCoV replication and alleviated PDCoV-induced apoptosis, implying that EP inhibited PDCoV replication and alleviated PDCoV-induced apoptosis via p38/MAPK signaling pathway. Collectively, ergosterol peroxide can protect piglets from PDCoV, revealing the potential of EP for development as a promising strategy for treating and controlling the infection of PDCoV.

An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online-solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry.

RATIONALE: Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin. METHODS: An online solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry (online-SPE-LC-HRMS) method was developed and applied for the determination of digoxin in plasma. The online SPE-LC steps included pretreatment and separation of plasma samples that were carried out using a Waters Oasis HLB cartridge and XBridge Shield RP18 column, respectively. A high-resolution Q Orbitrap mass spectrometer with targeted-selected ion monitoring in negative scan mode was applied to monitor formate-adduct ions [M + HCOO]- m/z 825.42781 for digoxin. RESULTS: Linearity was shown over the range 0.1-10 ng mL-1 for digoxin with correlation coefficients of R2 > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1 ng mL-1 . Extraction recoveries ranged from 82.61% to 94.28% for digoxin. The intra- and inter-day precision values were < 5.53% with accuracy ranging from 84.97% to 96.75%. The total running time was 10 min for each sample. CONCLUSION: The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.

Thermodynamics Analysis and Removal of P in a P-(M)-H2O System.

In order to efficiently remove phosphorus, thermodynamic equilibrium diagrams of the P-H2O system and P-M-H2O system (M stands for Fe, Al, Ca, Mg) were analyzed by software from Visual MINTEQ to identify the existence of phosphorus ions and metal ions as pH ranged from 1 to 14. The results showed that the phosphorus ions existed in the form of H3PO4, H2PO4-, HPO42-, and PO43-. Among them, H2PO4- and HPO42- were the main species in the acidic medium (99% at pH = 5) and alkaline medium (97.9% at pH = 10). In the P-Fe-H2O system ((P) = 0.01 mol/L, (Fe3+) = 0.01 mol/L), H2PO4- was transformed to FeHPO4+ at pH = 0-7 due to the existence of Fe3+ and then transformed to HPO42- at pH > 6 as the Fe3+ was mostly precipitated. In the P-Ca-H2O system ((P) = 0.01 mol/L, (Ca2+) = 0.015 mol/L), the main species in the acidic medium was CaH2PO4+ and HPO42-, and then transformed to CaPO4- at pH > 7. In the P-Mg-H2O system ((P) = 0.01 mol/L, (Mg2+) = 0.015 mol/L), the main species in the acidic medium was H2PO4- and then transformed to MgHPO4 at pH = 5-10, and finally transformed to MgPO4- as pH increased. The verification experiments (precipitation experiments) with single metal ions confirmed that the theoretical analysis could be used to guide the actual experiments.

Chlorogenic acid prevents vancomycin-induced nephrotoxicity without compromising vancomycin antibacterial properties.

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1ß and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

Rutin Attenuates Vancomycin-Induced Nephrotoxicity by Ameliorating Oxidative Stress, Apoptosis, and Inflammation in Rats.

Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment of serious infections caused by multiresistant Gram-positive bacteria. This study investigated the renal protective activity of rutin in a rat model of VCM-induced kidney injury in male Wistar rats. VCM administered intraperitoneally at 200 mg/kg twice daily for 7 successive days resulted in significant elevation of blood urea nitrogen and creatinine, as well as urinary N-acetyl-ß-D-glucosaminidase. Coadministration of VCM with oral rutin at 150 mg/kg significantly reduced these markers of kidney damage. Rutin also significantly attenuated VCM-induced oxidative stress, inflammatory cell infiltration, apoptosis, and decreased interleukin-1ß and tumor necrosis factor alpha levels (all P < 0.05 or 0.01) in kidneys. Renal recovery from VCM injury was achieved by rutin through increases in Nrf2 and HO-1 and a decrease in NF-κB expression. Our results demonstrated a protective effect of rutin on VCM-induced kidney injury through suppression of oxidative stress, apoptosis, and downregulation of the inflammatory response. This study highlights a role for oral rutin as an effective intervention to ameliorate nephrotoxicity in patients undergoing VCM therapy.

Kaempferol-3-O-glucorhamnoside inhibits inflammatory responses via MAPK and NF-κB pathways in vitro and in vivo.

Klebsiella pneumoniae causes severe infections including pneumonia and sepsis and treatments are complicated by increased levels of antibiotic resistance. We have identified a flavonoid kaempferol-3-O-glucorhamnoside derived from the plant Thesium chinense Turcz that possessed potent anti-inflammatory effects in K. pneumoniae infected mice. Administration of kaempferol-3-O-glucorhamnoside before bacterial challenge effectively suppressed expression of the major inflammatory cytokines TNF-α, IL-6, IL-1ß and PGE2 and ameliorated lung edema. In addition, administration of this compound to cultured RAW macrophages or Balb/c mice resulted in the suppression of NFκB and MAP kinase phosphorylation indicating an inhibitory effect on inflammation in vitro and in vivo. Kaempferol-3-O-glucorhamnoside also decreased ROS levels and overall oxidative stress in lungs and in cultured cells generated by K. pneumoniae exposure. Taken together, kaempferol-3-O-glucorhamnoside is a potent anti-inflammatory in vitro and in vivo and is a promising therapeutic agent for treating K. pneumoniae infections in the clinic.

Organocatalytic C(sp3)-H Functionalization of 5-Methyl-2,3-dihydrofuran Derivatives with Trifluoropyruvates via a Sequential exo-Tautomerization/Carbonyl-Ene Process.

An organocatalytic C(sp3)-H functionalization of 5-methyl-2,3-dihydrofuran derivatives with trifluoropyruvates was achieved via a sequential exo-tautomerization/carbonyl-ene process, providing the biologically important CF3-substituted 2,3-dihydrofurans in high yields. This method featured mild metal-free conditions, good chemoselectivity, and easy scalability.

Cefquinome-Loaded Microsphere Formulations in Protection against Pneumonia with Klebsiella pneumonia Infection and Inflammatory Response in Rats.

PURPOSE: This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model. METHODS: Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. In the KPD + CEQ-PLGA-MS and KPD + INJ groups, infected rats were intravenously injected with 12.5 mg/kg body weight CEQ-PLGA-MS and CEQ-INJ, respectively. RESULTS: Compared to CEQ-INJ treatment group, CEQ-PLGA-MS treatment further decreased the number of bacteria colonies (decreased to 1.94 lg CFU/g) in lung tissues and the levels of inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-4 (p < 0.05 or p < 0.01) in bronchoalveolar lavage fluid at 48 h. Consistently, a significant decreases of scores of inflammation severity were showed at 48 h in the KPD + CEQ-PLGA-MS treatment group, compared to the KPD + CEQ-INJ treatment group. CONCLUSION: Our results reveal that CEQ-PLGA-MS has the better therapeutic effect than CEQ-INJ for Klebsiella pneumonia lung infections in rats. The vehicle of CEQ-PLGA-MS as the promising alternatives to control the lung infections with the important pathogens.

The effect characteristics of temperature on stroke mortality in Inner Mongolia and globally.

The current study investigated the correlation between stroke mortality and temperature. Monthly and seasonal variations in stroke mortality were plotted and daily stroke-related deaths were calculated. The lag times were calculated using the time series analysis. The correlation between stroke incidence and the diurnal temperature range (DTR) was analyzed using case-crossover analysis. Global stroke mortality was described in five latitudes. In the eastern region of Inner Mongolia, the stroke mortality was 174.18/105, about twice of that of the midwestern regions (87.07/105), and temperature was negatively correlated with stroke mortality. Mortality peaked in the winter and troughed in the summer (χ2 = 13.634, P < 0.001). The days in which stroke-related deaths were greater than ten occurred between late October and early April. The effect of temperature on stroke incidence occurred during a lag time of 1 (P = 0.024) or 2 months (P = 0.039). A DTR over 13 °C was positively correlated (r = 0.95, P = 0.004) with stroke with a lag time of 1 day. The effect of temperature on stroke was shown to be the same for various populations. As the latitude increases, stroke mortality also increases with latitudes > 40°; the highest mortality was 188.05/105 at the highest latitude. Only in relatively cold regions as the temperature decreases does stroke mortality increase for various populations. Differences in the time lag as well as in the DTR lag and DTR critical point vary for both the temperature and region.

Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress.

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 µM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.

Distribution and elimination of quinocetone and its major metabolites in Cherry Valley ducks.

We examined the tissue distribution and elimination of quinocetone (QCT) and its major metabolites 1-desoxyquinocetone (1-DQCT), di-desoxyquinocetone (BDQCT), and 3-methyl-quinoxaline-2-carboxylic (MQCA) in ducks. The analytes were simultaneously quantitated using a UPLC-MS/MS method after oral administration of QCT at 100 mg·kg-1 day-1 for 7 days. We found that QCT and its major metabolites were widely distributed in duck tissues. The concentrations indicated that the primary compound in the liver, kidney, and heart was MQCA and the primary compound in the stomach, intestine, spleen, and lung was QCT. We also identified that MQCA was the most appropriate compound for QCT residue monitoring. The liver and kidney are the primary QCT target organs in ducks, and this study provides clear monitoring tools and important data to evaluate its safety.

A Comparison of Two Methods for the Preparation Cefquinome-Loaded Gelatin Microspheres for Lung Targeting.

PURPOSE: The aim of this study was to prepare CEQ-loaded gelatin microspheres and compare two preparation methods, evaluate targeting to the lungs. METHODS: Gelatin microspheres containing CEQ were prepared by an emulsion cross-linking method (ECLM) and a spray-drying method (SDM) and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release. RESULTS: The microspheres prepared by ECLM gave a drug loading (DL) of 19.4 ± 2.4% and an entrapment efficiency (EE) of 80.8 ± 3.2%. The microspheres prepared by SDM resulted in a DL value of 20.8 ± 2.7% and an EE of 95.3 ± 3.8%. The average particle size of microspheres was 7-30 µm by both methods and both preparations sustained CEQ release for 36 h in the target tissue (lungs). The in vitro release profile of the microspheres matched the Korsmeyer-Peppas release pattern. In vivo studies identified the lung as the target tissue and the region of maximum CEQ release. Histopathological examination showed a partial lung inflammation that disappeared spontaneously as the microspheres were biodegraded. In general, the formulations were safe. CONCLUSION: The well-sustained CEQ release from the microspheres revealed its suitability as a drug delivery vehicle that minimized injury to healthy tissues while achieving the accumulation of therapeutic drug for lung targeting. The intravenous administration of CEQ gelatin microspheres prepared by SDM is of potential value in treating lung diseases in animals.