An Experimental Study: Benefits of Digoxin on Hepatotoxicity Induced by Methotrexate Treatment

Purpose. The aim of the study is to examine the possible therapeutic effects of a known cardiac glycoside, digoxin, on a rat model of MTX-induced hepatotoxicity. Methods. The study was conducted on twenty-four male rats. While eighteen rats received a single dose of 20 mg/kg MTX to obtain an injured liver model, six rats constituted the control group. Also, the eighteen liver toxicity model created rats were equally divided into two groups, one of which received digoxin 0.1 mg/kg/day digoxin (Group 1) and the other group (Group 2) was given saline (% 0.9NaCl) with a dose of 1 ml/kg/day for ten days. Following the trial, the rats were sacrificed to harvest blood and liver tissue samples to determine blood and tissue MDA, serum ALT, plasma TNF-α, TGF-β, IL-6, IL-1-Beta, and PTX3 levels. Results. MTX’s structural and functional hepatotoxicity was observable and evidenced by relatively worse histopathological scores and increased biochemical marker levels. Digoxin treatment significantly reduced the liver enzyme ALT, plasma TNF-α, TGF-β, PTX3, and MDA levels and decreased histological changes in the liver tissue with MTX-induced hepatotoxicity in the rat model. Conclusion. We suggest that digoxin has an anti-inflammatory and antihepatotoxic effect on the MTX-induced liver injury model.

Label-free functional and structural imaging of liver microvascular complex in mice by Jones matrix optical coherence tomography

We demonstrate label-free imaging of the functional and structural properties of microvascular complex in mice liver. The imaging was performed by a custom-built Jones-matrix based polarization sensitive optical coherence tomography (JM-OCT), which is capable of measuring tissue’s attenuation coefficient, birefringence, and tiny tissue dynamics. Two longitudinal studies comprising a healthy liver and an early fibrotic liver model were performed. In the healthy liver, we observed distinctive high dynamics beneath the vessel at the initial time point (0 h) and reappearance of high dynamics at 32-h time point. In the early fibrotic liver model, we observed high dynamics signal that reveals a clear network vascular structure by volume rendering. Longitudinal time-course imaging showed that these high dynamics signals faded and decreased over time.

Hybrid Additive Fabrication of a Transparent Liver with Biosimilar Haptic Response for Preoperative Planning

Due to the complexity of liver surgery, the interest in 3D printing is constantly increasing among hepatobiliary surgeons. The aim of this study was to produce a patient-specific transparent life-sized liver model with tissue-like haptic properties by combining additive manufacturing and 3D moulding. A multistep pipeline was adopted to obtain accurate 3D printable models. Semiautomatic segmentation and registration of routine medical imaging using 3D Slicer software allowed to obtain digital objects representing the structures of interest (liver parenchyma, vasculo-biliary branching, and intrahepatic lesion). The virtual models were used as the source data for a hybrid fabrication process based on additive manufacturing using soft resins and casting of tissue-mimicking silicone-based blend into 3D moulds. The model of the haptic liver reproduced with high fidelity the vasculo-biliary branching and the relationship with the intrahepatic lesion embedded into the transparent parenchyma. It offered high-quality haptic perception and a remarkable degree of surgical and anatomical information. Our 3D transparent model with haptic properties can help surgeons understand the spatial changes of intrahepatic structures during surgical manoeuvres, optimising preoperative surgical planning.

Salidroside Alleviates Lipid Metabolism Disorder and Inflammatory Response, and Promotes Hepatocyte Proliferation in Fatty Liver-Hemorrhagic Syndrome of Laying Hens

Background: Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. This disease is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protective effects on mitochondrial function, attenuates cell apoptosis and inflammation, and promotes strong antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo.Results: Results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2, as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes. Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-β, while inhabited the PI3K inhibitor. Additionally, we found that high-fat diet-induced FLHS of laying hens in vivo resulted in heavier body weight, liver weight, and abdominal fat weight, and severer steatosis in histology, compared with the control group (Con). However, SDS maintained lighter body weight, liver weight, and abdominal fat weight and alleviate hepatic steatosis in Model+SDS group. In addition, high-fat diet-induced FLHS (Model) of laying hens had higher total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) levels in serum than Con group, while SDS maintained low TC, TG, ALT, and AST levels and high Superoxide dismutase (SOD) activity in Model+SDS group. Moreover, SDS decreased the mRNA expression abundances of PPARγ, SCD, and FAS in liver, whereas increased those of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1β, IL-6, and IL-8 in Model+SDS group.Conclusions: Generally, SDS attenuated OA-induced ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the pathway PI3K/AKT/Gsk3-β in OA-induced fatty liver model in vitro, and alleviated high-fat diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.

Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose

Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to produce fatty liver more efficiently than the high-fat diet medaka model that has been used to date. We compared the GAN (Gubra-Amylin nonalcoholic steatohepatitis) diet, which has been used in recent years to induce fatty liver in mice, and the high-fat diet (HFD). Following administration of the diets for three months, enlarged livers and pronounced fat accumulation was noted. The GAN group had large fat vacuoles and lesions, including ballooning, compared to the HFD group. The GAN group had a higher incidence of lesions. When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver. The medaka fatty liver model administered with GAN will be useful in future fatty liver research.

Feasibility of a Drug-Releasing Radiofrequency Ablation System in a Porcine Liver Model

The objective of this study was to investigate the feasibility of a newly developed anticancer drug-releasing radiofrequency ablation (RFA) system in a porcine liver model. A 15-gauge drug-releasing cooled wet electrode (DRCWE) was newly developed to improve the RFA efficacy for creating a large ablation as well as for simultaneously delivering an anticancer drug to the tumor margin. Nine ablations in three pigs were performed by the DRCWE. The sectioned liver specimens were evaluated by measuring the ablation zone by a positron emission tomography/magnetic resonance imaging examination to investigate whether 18F-fluorodeoxyglucose was exactly diffused. Volumes of the ablation zones released drug injection volumes, circularity, retention rate defined as the ratio between an estimated and injection dose, and the standard uptake value were assessed. The drug-releasing RFA was technically successful without procedural-related complications. During the procedure, the color changes of the ablated zones of the liver were observed in all specimens. The mean drug injection volume was higher than the ablated volumes (17.21 ± 2.85 vs. 15.22 ± 2.30 cm3) and the circularity was 0.72 ± 0.08. Moreover, the retention rate was 72.89% ± 4.22% and the mean standard uptake value was 0.44 ± 0.05. The drug-releasing RFA system was feasible not only for local ablation but also for the delivery of anticancer drugs. The results of this study indicate that this novel strategy of localized RFA with a drug delivery system could be a promising option for the prevention of local recurrence rates.