Chemosensitivity of three patient-derived primary cultures of canine pericardial mesothelioma by single-agent and combination treatment.

Introduction: Canine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the treatment of canine mesotheliomas. We aimed to compare the antitumor effects of single-agent and combination chemotherapeutic agents on patient-derived primary cultures of canine pericardial mesothelioma established in this study. We planned to generate xenograft models for future studies. Material and methods: Effusion samples were collected from three dogs with histologically diagnosed pericardial mesothelioma and used for primary culture. Cultured cells were characterized by immunostaining for pan-cytokeratin AE1/AE3, vimentin, Wilms' tumor suppressor gene 1 (WT1), and cytokeratin 5 (CK5). To assess the tumorigenic properties of cells in the effusion and generate a xenograft model, the cell suspension was injected into a severe combined immunodeficient (SCID) mouse either subcutaneously (SC) or intraperitoneally (IP). Lastly, chemosensitivity of established primary cultures against four drugs, doxorubicin, vinorelbine, carboplatin, and gemcitabine, by single-agent treatment as well as combination treatment of carboplatin at a fixed concentration, either 10 or 100 µM, and gemcitabine at different concentrations ranging from 0-1000 µM was assessed by cell viability assay. Results: Primary cultures were successfully generated and characterized by dual positivity for AE1/AE3 and vimentin and positive staining for WT-1 and CK5, confirming the mesothelial origin of the cells. In the xenograft models, SC mouse developed a subcutaneous mass, whereas IP mouse developed multiple intraperitoneal nodules. The masses were histopathologically consistent with mesotheliomas. The chemosensitivity assay revealed that carboplatin had the highest anti-tumor effects among the four tested single-agent treatments. Furthermore, carboplatin at 100 µM combined with gemcitabine at clinically relevant doses demonstrated the augmented anti-tumor effects compared to single-agent treatment. Discussion and conclusion: Primary cultures and xenograft models generated in this study could be useful tools for in vitro and in vivo studies of canine mesothelioma. Carboplatin is a highly effective chemotherapeutic agent against canine mesothelioma when used as a sole agent and in combination with gemcitabine.

Cyanoacrylate closure for arteriovenous fistula in the lower extremity with saphenous vein insufficiency.

A lower extremity arteriovenous fistula (AVF) is sometimes associated with venous disease following venous hypertension, especially when the saphenous vein is the main return route. This can cause venous dilation, leading to valve insufficiency. A complete cure can be difficult in cases with multiple vascular branches. We report three surgical cases of lower extremity AVF with saphenous vein insufficiency. All patients had saphenous vein insufficiency with long duration leg symptoms and underwent full-length occlusion of saphenous vein using cyanoacrylate closure. Substantial improvements in leg symptoms and appearance were observed immediately after surgery in all three patients. Cyanoacrylate closure could be a treatment option for lower extremity AVF.

Derivation of a new model of lung adenocarcinoma using canine lung cancer organoids for translational research in pulmonary medicine.

Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.

Establishment of an experimental model of canine malignant mesothelioma organoid culture using a three-dimensional culture method.

Canine malignant mesothelioma (cMM) is a rare and drug-resistant malignant tumor. Due to few patients and experimental models, there have not been enough studies to demonstrate the pathogenesis of the disease and novel effective treatment for cMM. Since cMM resembles human MM (hMM) in histopathological characteristics, it is also considered a promising research model of hMM. Compared with conventional 2-dimensional (2D) culture methods, 3-dimensional (3D) organoid culture can recapitulate the properties of original tumor tissues. However, cMM organoids have never been developed. In the present study, we for the first time generated cMM organoids using the pleural effusion samples. Organoids from individual MM dogs were successfully generated. They exhibited the characteristics of MM and expressed mesothelial cell markers, such as WT-1 and mesothelin. The sensitivity to anti-cancer drugs was different in each strain of cMM organoids. RNA sequencing analysis showed cell adhesion molecule pathways were specifically upregulated in cMM organoids compared with their corresponding 2D cultured cells. Among these genes, the expression level of E-cadherin was drastically higher in the organoids than that in the 2D cells. In conclusion, our established cMM organoids might become a new experimental tool to provide new insights into canine and human MM therapy.

Technology for Fundamental Improvement of an Extremely Low-Quality Video Signal for Use in Fine Focusing and Astigmatism Correction in Scanning Electron Microscopy.

This study describes important techniques for production of a series of video signals for use in fine focusing operations and near-perfect astigmatism correction in the general-purpose scanning electron microscopy (SEM) field. These techniques can enhance the stability of the signal greatly when used for focusing. As two particularly important fundamental techniques, SEM image acquisition with priority given to the signal-to-noise ratio and signal reinforcement based on the active image processing concept were utilized fully. The performance improvement was evaluated using the case of a previously reported support system for fine focusing and astigmatism correction based on image covariance. The method is almost completely robust against noise within practical limits and allows for focusing and astigmatism correction for even extremely noisy SEM images. The results of this study may be useful not only in the SEM field but also in many fields that use weak signals.

Usefulness of Ultrasound Shear Wave Elastography for Detection of Quadriceps Contracture in Immobilized Rats.

Quadriceps contracture is an abnormal pathological shortening of the muscle-tendon unit. To improve the prognosis of quadriceps contracture, improvement of its diagnostic method is needed. In this study, we evaluated the diagnostic utility of ultrasound shear wave elastography in a rat model of quadriceps contracture induced by immobilization. Fifty Wistar rats were randomly divided into control and immobilization groups. During up to 4 weeks of joint immobilization, the quadriceps elastic modulus, muscle hardness, creatinine phosphokinase levels, joint range of motion, histopathologic parameters, and levels of fibrosis-associated mRNA expression were measured every week in the immobilization and control groups and compared. In the immobilization group, the elastic modulus gradually but significantly increased (p < 0.05) throughout the immobilization period. However, muscle hardness and serum creatinine phosphokinase levels only increased at 1 and 2 weeks after the start of immobilization, respectively. Muscle atrophy and shortening progressed throughout the immobilization group. Collagen type I and III, α-SMA protein, and mRNA expression of IL-1ß and TGF-ß1 significantly increased (p < 0.05) throughout in the immobilization group. Ultrasound shear wave elastography is the most useful method for clinical assessment of muscle contracture.

Protective Effect on Pancreatic Acinar Cell by Maintaining Cardiac Output in Canine Heart Failure Model With Decreased Pancreatic Blood Flow.

Heart failure cause hypoperfusion-induced damage to abdominal organs due to decreased cardiac output (CO). Using a model dog with heart failure caused by rapid ventricular pacing (RVP), we have previously demonstrated that a decrease in CO reduces pancreatic blood flow (PBF). Furthermore, we have revealed that pancreatic acinar cell atrophy, which is a change in the pre-stage of pancreatitis was caused. However, the mechanism by which pancreatic acinar cell atrophy was caused in RVP dogs remains unknown. This study aimed to clarify the association between cardiac function, PBF, and histopathological changes in pancreatic acinar cells by administrating pimobendan, which increase CO, to RVP dogs. RVP dogs were divided into the control group (no medication, n = 5) and the pimobendan group (pimobendan at 0.25 mg/kg BID, n = 5). Non-invasive blood pressure measurement, echocardiography, and contrast-enhanced ultrasonography for PBF measurement were performed before initiating RVP and at 4 weeks after initiating RVP (4 weeks). At 4 weeks, the decreases in CO, mean blood pressure and PBF due to RVP were suppressed in pimobendan group. Furthermore, histopathological examination showed no changes in pancreatic acinar cells in the pimobendan group. Overall, it was clarified that the decrease in PBF due to cardiac dysfunction was a direct cause of pancreatic acinar cell atrophy. This suggests that maintaining PBF is clinically important for treating dogs with heart failure. In addition, these findings offer a reliable basis for developing new therapeutic strategies for heart failure in dogs, that is, pancreatic protection.

Highly Reliable Method to Obtain a Correlation Coefficient Unaffected by the SEM Noise Component for Examining the Degree of Specimen Damage due to Electron Beam Irradiation.

A correlation coefficient is often used as a measure of the strength of a linear relationship (i.e., the degree of similarity) between two sets of data in a variety of fields. However, in the field of scanning electron microscopy (SEM), it is frequently difficult to properly use the correlation coefficient because SEM images generally include severe noise, which affects the measurement of this coefficient. The current study describes a method of obtaining a correlation coefficient that is unaffected by SEM noise in principle. This correlation coefficient is obtained from a total of four SEM images, comprising two sets of two images with identical views, by calculating several covariance values. Numerical experiments confirm that the measured correlation coefficients obtained using the proposed method for noisy images are equal to those for noise-free images. Furthermore, the present method can be combined with a highly accurate and noise-robust position alignment as needed. As one application, we show that it is possible to immediately examine the degree of specimen damage due to electron beam irradiation during a certain SEM observation, which has been difficult until now.

Histopathological changes in the pancreas due to decreased pancreatic blood flow in a canine tachycardia-induced cardiomyopathy model.

In dogs, pancreatic acinar cell injury is thought to be caused by decreased pancreatic blood flow due to heart failure. In previous our report, it demonstrated that decreased heart function causes a significant decrease in pancreatic blood flow in heart failure dog model caused by rapid ventricular pacing (RVP). However, the types of histopathological changes remain unclear. We aimed to verify the types of histopathological changes occurring in the pancreatic tissue due to decreased heart function. After RVP for 4 weeks, atrophy of pancreatic acinar cells, characterized by a decrease in zymogen granules, was observed in all areas of the pancreas. In conclusion, the result of this study suggests that attention should be paid to ischemia/hypoperfusion injury in the pancreas.

Effect of edaravone against cisplatin-induced chronic renal injury.

Cisplatin has been widely used as an anticancer agent for a wide range of tumors, but it had nephrotoxicity that was mainly caused by oxidative stress. Edaravone, a free radical scavenger, has reportedly been validated to have a protective effect against renal injury induced by reactive oxygen species. However, most of these reports are against AKI, and few studies have examined the effect of chronic renal injury. In this study, we investigate the effect of edaravone on cisplatin nephropathy in the chronic phase. Twenty-five male Wistar rats were divided into five groups: control, cisplatin, cisplatin + edaravone 1 mg kg-1, cisplatin + edaravone 10 mg kg-1, and cisplatin + edaravone 100 mg kg-1. Edaravone was administrated intraperitoneally every other day for 5 weeks, starting 1 week before cisplatin administration (6 mg kg-1, i.p.). As a result, proximal tubule injury, interstitial fibrosis, and mononuclear cell infiltration were ameliorated histologically in the group of rats treated with high edaravone dose. In the cisplatin group, the number of α-SMA-, CD68-, and CD3-positive cells increased markedly compared with the Control group, but these numbers were significantly decreased by higher doses of co-administered edaravone. While there was no clear mRNA expression variation in antioxidant enzymes, the apoptosis-promoting factors, caspase8, were markedly reduced in the high-dose edaravone co-administration group compared with the cisplatin group. In conclusion, our results suggested that cisplatin-induced renal injury in the chronic phase was ameliorated by edaravone.

Metformin prevents the development of monocrotaline-induced pulmonary hypertension by decreasing serum levels of big endothelin-1.

Pulmonary hypertension (PH) is a disease with poor prognosis, and it is characterized by the progressive elevation of pulmonary vascular resistance and pressure. Various factors are associated with the pathology of PH, including AMP-activated protein kinase (AMPK) deficiency. The present study aimed to evaluate the therapeutic effect of metformin, an AMPK activator, in a monocrotaline (MCT)-induced PH rat model. Rats were randomly divided into the following three groups: i) Saline-injected group (sham group); ii) monocrotaline (MCT)-injected group (PH group); iii) MCT-injected and metformin-treated group (MT group). Four weeks following MCT injection, cardiac ultrasonography, invasive hemodynamic measurements, measurement of serum levels of big endothelin-1 (big ET-1) and histological analysis were performed to evaluate the effect of metformin treatment in PH. Pulmonary arterial pressure and serum big ET-1 concentrations were reduced in the MT group compared with the PH group. Medial wall thickness and wall area of the pulmonary arterioles in the MT group were decreased compared with the PH group. Comparing the right heart functional parameters among groups revealed that the acceleration time/ejection time ratio improved in the MT group compared with the PH group. Thus, the present study demonstrated the efficacy of metformin in an MCT-induced PH rat model and suggested that metformin may be a valuable, potential novel therapeutic for the treatment of PH.

Increased proportion of apoptotic cells in cat kidney tissues infected with feline morbillivirus.

In order to study potential pathogenic mechanisms of feline morbillivirus (FeMV) in infected kidney cells, we performed a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and an immunofluorescence assay (IFA) with an anti-FeMV P protein antibody on a total of 38 cat kidney tissues, 12 of which were positive for FeMV. Among these samples, we detected significantly larger numbers of apoptotic cells in FeMV-positive tissues than in FeMV-negative tissues, and in these tissues, a substantial percentage of TUNEL-positive (TUNEL+) cells contained the FeMV P protein (mean, 37.4; range, 17.4-82.9), suggesting that induction of apoptosis may be an important mechanism for pathological changes associated with FeMV infection in cat kidney tissues.

Applying Fast Scanning Method Coupled with Digital Image Processing Technology as Standard Acquisition Mode for Scanning Electron Microscopy.

This study proposes an efficient and fast method of scanning (e.g., television (TV) scan) coupled with digital image processing technology to replace the conventional slow-scan mode as a standard model of acquisition for general-purpose scanning electron microscopy (SEM). SEM images obtained using the proposed method had the same quality in terms of sharpness and noise as slow-scan images, and it was able to suppress the adverse effects of charging in a full-vacuum condition, which is a challenging problem in this area. Two problems needed to be solved in designing the proposed method. One was suitable compensation in image quality using the inverse filter based on characteristics of the frequency of a TV-scan image, and the other to devise an accurate technique of image integration (noise suppression), the position alignment of which is robust against noise. This involved using the image montage technique and estimating the number of images needed for the integration. The final result of our TV-scan mode was compared with the slow-scan image as well as the conventional TV-scan image.

Pericardial Mesothelioma in a Dog: The Feasibility of Ultrasonography in Monitoring Tumor Progression.

A 6-year-old neutered male Yorkshire Terrier presented with recurrent pericardial effusion. Although clinical examinations including computed tomography were inconclusive, an exploratory thoracotomy revealed multiple small nodules and plaques on the inner surface of the pericardial sac (Day 1). A subtotal pericardiectomy was performed to prevent cardiac tamponade due to the increasing pericardial effusion, and the resected section of the pericardium was histopathologically diagnosed with mesothelioma. After surgery, chemotherapy with intrathoracic carboplatin was commenced. During the course of the treatment, a detailed follow-up ultrasonographic scan was performed to detect early lesions disseminated on the pleura, originating from the primary pericardial mesothelioma. On Day 101, the minute pleural nodules, which were disseminated lesions as predicted, were successfully imaged by ultrasonography. As the clinical stage advanced, the nodules were observed to gradually increase in size and number, implying tumor progression. These observations highlight the feasibility of ultrasonography in detecting minute disseminated lesions at an early stage, monitoring tumor progression, and thereby, predicting the prognosis of canine pericardial mesothelioma.

Dimethyl fumarate ameliorates cisplatin-induced renal tubulointerstitial lesions.

Dimethyl fumarate (DMF) has an antioxidant effect by activating the nuclear factor erythroid 2-related transcription factor 2 (Nrf2). Cisplatin (CIS) has nephrotoxicity as a frequently associated side effect that is mainly mediated by oxidative stress. In this study, we investigated whether the DMF-mediated antioxidative mechanism activated by Nrf2 can ameliorate CIS-induced renal tubulointerstitial lesions in rats. In Experiments 1 and 2, 25 five-week-old male Wistar rats were divided into five groups: control, CIS, and 3 CIS+DMF groups (300, 1,500, and 7,500 ppm in Experiment 1; 2,000, 4,000, and 6,000 ppm in Experiment 2). Rats were fed their respective DMF-containing diet for 5 weeks. CIS was injected 1 week after starting DMF administration, and the same volume of saline was injected into the control group. CIS-induced severe tubular injury, such as necrosis and degeneration in the outer segment of the outer medulla, was inhibited in the 7,500 ppm DMF group and ameliorated in all DMF groups in Experiment 2. Increased interstitial mononuclear cell infiltration and increased Sirius red-positive areas were also observed in CIS-administered groups, and these increases tended to be dose-dependently inhibited by DMF co-administration in Experiments 1 and 2. The numbers of α-smooth muscle actin (SMA)-positive myofibroblasts, CD68-positive macrophages, and CD3-positive lymphocytes observed in the peritubular area also increased with CIS administration, and these increases were dose-dependently inhibited by DMF co-administration. Moreover, renal cortical mRNA expression of Nrf2-related genes such as NQO1 increased in DMF groups. This investigation showed that DMF ameliorates CIS-induced renal tubular injury via NQO1-mediated antioxidant mechanisms and reduces the consequent tubulointerstitial fibrosis.

Contrasting Effects of Inhibition of Phosphodiesterase 3 and 5 on Cardiac Function and Interstitial Fibrosis in Rats With Isoproterenol-Induced Cardiac Dysfunction.

Myocardial relaxation and stiffness are influenced by fibrillar collagen content. Cyclic nucleotide signaling regulators have been investigated targeting more effective modulation of collagen deposition during myocardial healing process. To assess the effects of phosphodiesterase type 3 and phosphodiesterase type 5 inhibitors on cardiac function and left ventricular myocardial fibrosis in catecholamine-induced myocardial injury, sildenafil and pimobendan were administered to male Wistar rats 24 hours after isoproterenol injection. Echocardiography and electrocardiogram were performed to assess kinetic and rhythm changes during 45 days of drug administration. At the end of study, type I and type III collagen were measured through immunohistochemistry analysis, and left ventricular pressure was assessed through invasive method. Echocardiography assessment showed increased relative wall thickness at 45 days in pimobendan group with significant diastolic dysfunction and increased collagen I deposition compared with nontreated positive group (3.03 ± 0.31 vs. 2.73 ± 0.28%, P < 0.05). Diastolic pressure correlated positively with type I collagen (r = 0.54, P < 0.05). Type III collagen analysis did not demonstrate difference among the groups. Sildenafil administration attenuated type I collagen deposition (2.15 ± 0.51 vs. positive group, P < 0.05) and suggested to be related to arrhythmic events. Arrhythmic events were not related to the quantity of fibrillar collagen deposition. Although negative modulation of collagen synthesis through cyclic nucleotides signaling have shown promising results, in this study, pimobendan postconditioning resulted in increased collagen type I formation and severe diastolic dysfunction while sildenafil postconditioning reduced collagen type I deposition and attenuated diastolic dysfunction.

Association of feline morbillivirus infection with defined pathological changes in cat kidney tissues.

Feline morbillivirus (FeMV) is an emerging member of morbillivirus discovered in 2012. Although association of FeMV infection with kidney diseases in cats has been suggested, the pathogenicity of the virus has not been clear to date. To study the association between FeMV infection and pathological changes in kidney tissues of infected cats, we performed immunohistochemistry and immunofluorescent assays to detect FeMV antigens and analyzed the effect of FeMV infection on the pathological changes in the kidney tissues. In 38 kidney tissue samples from cats, some tissue injury scores were significantly higher when the FeMV antigens were detected, especially those for the tubular tissues in which the FeMV antigens were mostly localized. Pathological changes associated with the FeMV antigens included the ones typically found in chronic kidney diseases, such as interstitial cell infiltration, glomerulosclerosis, tubular atrophy and fibrosis. We also detected some feline IgG localizations in glomerular tissues, though co-localization or significant association with the FeMV antigens were not found. Our study confirms the association of FeMV infection with some kidney tissue injuries and provides additional information about roles of FeMV infection in chronic kidney diseases.

Cloning of carrier cells infected with oncolytic adenovirus driven by midkine promoter and biosafety studies.

BACKGROUND: A549 carrier cells infected with oncolytic adenovirus can induce complete tumor reduction of subcutaneous ovarian tumors but not intraperitoneal disseminated ovarian tumors. This appears to be a result of the insufficient antitumor effect of A549 carrier cells. Therefore, in the present study, we cloned a novel carrier cell with the aim of improving the antitumor effects. METHODS: Carrier cells infected with oncolytic adenovirus AdE3-midkine with a midkine promoter were cloned by limiting dilution. We examined the antitumor effects of these cells on subcutaneous and intraperitoneal OVHM ovarian tumors in a syngeneic mouse model. Biosafety tests were conducted in beagle dogs and rabbits. RESULTS: We cloned EHMK-51-35 carrier cells with 10-fold higher antitumor effects compared to A549 carrier cells in vitro. EHMK-51-35 carrier cells co-infected with AdE3-midkine and Ad-mGM-CSF induced a 100% complete tumor reduction in subcutaneous tumors and a 60% reduction of intraperitoneal disseminated tumors. Single-dose acute toxicity test on beagle dogs with EHMK-51-35 carrier cells co-infected with AdE3-midkine and Ad-cGM-CSF showed no serious side effects. Biologically active adenoviruses were not detected in the blood, saliva, feces, urine or whole organs. In a chronic toxicity test, VX2 tumors in rabbits were injected five times with EHMK-51-35 carrier cells infected with AdE3-midkine and these rabbits showed no serious side effects. CONCLUSIONS: Significant antitumor effects and safety of cloned EHMK-51-35 carrier cells were confirmed in intraperitoneal ovarian tumors and toxicity tests, respectively. These findings will be extended to preclinical efficacy studies using dogs and cats, with the aim of conducting human clinical trials on refractory solid tumors.

Inhibitory effect of propolis on the development of AA amyloidosis.

In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.

The effect of ß-caryophyllene on nonalcoholic steatohepatitis.

The pathogenesis of nonalcoholic steatohepatitis (NASH) is not fully understood, but many studies have suggested that oxidative stress plays a key role. The methionine- and choline-deficient diet (MCD) administration model can reproduce histopathological features of human NASH and is widely used for investigating NASH. C57BL/6J mice have been used in many studies, but strain differences in pathogenesis have not been sufficiently investigated. We administred MCD to two mouse strains and then compared difference between strains and investigated the effects of ß-caryophyllene (BCP), which possesses an antioxidant effect, on development and progression of NASH. ICR and C57BL/6J mice were administred a control diet, MCD, MCD containing 0.02% BCP, or MCD containing 0.2% BCP. After 4 or 8 weeks, mice were sacrificed. In both strains, MCD administration induced hepatic steatosis and inflammation. These lesions were more severe in C57BL/6J mice than ICR mice, and liver fibrosis was observed at 8 weeks in C57BL/6J mice. These changes were attenuated by BCP coadministration. The mRNA expression of monocyte chemotactic and activating factor (MCP)-1 and fibrosis-related factors increased in C57BL/6J mice, and these increases were reduced by BCP coadministration. The mRNA expression of antioxidant-related factors decreased in both strains, and these decreases were attenuated by BCP coadministration. Based on these results, the C57BL/6J mouse was a more suitable model for MCD-induced NASH than the ICR mouse. In addition, it was suggested that antioxidant effect of BCP might suppressed the damage of hepatocytes caused by oxidative stress and following inflammation and fibrosis.