Hepatic Fatty Degeneration Research Articles

Chronic kidney disease in a giant panda (Ailuropoda melanoleuca): a case report

BackgroundChronic kidney disease (CKD) is a common cause of morbidity and mortality in captive wildlife species. However, CKD has been rarely documented in giant pandas.Case presentationThe following report describes a case of an eight-year-old female giant panda showing clinical signs of epistaxis, bloody diarrhea, polyuria, azotemia and anemia. The animal died despite of supportive treatments. Necropsy was performed. Grossly, both kidneys were shrunken and scarred with pallor. Subcutis edema and petechia on the epicardium of the heart were observed. The tissue samples were made into paraffin sections and stained by H.E and special staining including Periodic Acid-Schiff (PAS), von Kossa, Masson’s trichrome, Phosphotungstic acid-hematoxylin (PTAH), and Congo red. Histopathology examination revealed severe chronic tubulointerstitial nephritis with marked interstitial fibrosis, glomerulosclerosis, tubular atrophy and calcification in kidneys, and acute necrotizing hemorrhagic myocarditis with calcification in heart. Other lesions included intestinal hemorrhage, hepatic fatty degeneration and necrosis with hemosiderin, and splenic hemosiderin.ConclusionsIn summary, chronic kidney disease was finally diagnosed based on the association of clinical, gross, and histopathological findings. Heart failure secondary to CKD is the leading cause of death in this giant panda. The potential cause of CKD in this animal is possibly due to long term and uncontrolled hypertension. Blood pressure monitoring is essential in establishing the diagnosis and management of hypertension in giant panda.

Oxidative Stress Biomarkers Activities and Histological Changes in African Catfish (Clarias gariepinus) Exposed to Carwash Wastewater

The study evaluated the acute toxicity of vehicle wastewater on African catfish (Clarias gariepinus). With a weight range of 250–275.5g and a mean length of 23.5-28.5cm, 150 post-juvenile catfish were purchased from Dalar Kifi Fish Farm BUK New site road, Kano State, and acclimated in a tank for 14 days. Fish were exposed to different vehicle wastewater concentrations of 0.0, 20, 40, 60, and 80% v/v with 5-level exposure concentrations during the acute test (96 hours) in a Completely Randomized Design (CRD) employing renewal bioassay. The acute bioassay showed that the LC50 for the wastewater was 56 percent by volume at 96 hours. Compared to the control, the exposed fish exhibited abnormal swimming, erratic opercular movement, reflex loss, mucus secretion, increased air gulping with an increase in wastewater concentration. Except for water temperature, Biochemical Oxygen Demand (BOD) and pH, the remaining physicochemical parameters were not within the WHO/FAO recommended Standard The order of concentrations of the heavy metal in the wastewater was Cu > Pb > Cd > Cr > Ni. Antioxidant biomarker activities showed that Glutathione reductase (GSH) reduced in the same manner while Catalase (CAT) and Superoxide dismutase (SOD) activities rose considerably (P<0.05) in the liver and gill tissues. Histopathological changes observed in gill tissues were as follows: Hyperplasia, necrosis, primary and secondary lamellae distortion, and epithelial thickening distortion. Hepatic cell breakdown, fatty degeneration, cellular infiltration, localized fibrosis, and cellular necrosis were all visible in the liver tissues. It can be inferred that changes in the histology and activity of the oxidative stress enzymes in fish tissues after exposure to wastewater harmed the experimental fish. As a result of their effects on fish and other non-target aquatic biotas, it is advised that the competent authorities create initiatives to reduce the indiscriminate discharge of untreated vehicle wash wastewater.

Melatonin Alleviates PM2.5-Induced Hepatic Steatosis and Metabolic-Associated Fatty Liver Disease in ApoE-/- Mice

Background Exposure to fine particulate matter (PM2.5) is associated with the risk of developing metabolic-associated fatty liver disease (MAFLD). Melatonin is the main secreted product of the pineal gland and has been reported to prevent hepatic lipid metabolism disorders. However, it remains uncertain whether melatonin could protect against PM2.5-induced MAFLD. Methods and Results The purpose of our study was to investigate the mitigating effects of melatonin on hepatic fatty degeneration accelerated by PM2.5 in vivo and in vitro. Histopathological analysis and ultrastructural images showed that PM2.5 induced hepatic steatosis and lipid vacuolation in ApoE−/− mice, which could be effectively alleviated by melatonin administration. Increased ROS production and decreased expression of antioxidant enzymes were detected in the PM2.5-treated group, whereas melatonin showed recovery effects after PM2.5-induced oxidative damage in both the liver and L02 cells. Further investigation revealed that PM2.5 induced oxidative stress to activate PTP1B, which in turn had a positive feedback regulation effect on ROS release. When a PTP1B inhibitor or melatonin was administered, SP1/SREBP-1 signalling was effectively suppressed, while Nrf2/Keap1 signalling was activated in the PM2.5-treated groups. Conclusion Our study is the first to show that melatonin alleviates the disturbance of PM2.5-triggered hepatic steatosis and liver damage by regulating the ROS-mediated PTP1B and Nrf2 signalling pathways in ApoE−/− mice. These results suggest that melatonin administration might be a prospective therapy for the prevention and treatment of MAFLD associated with air pollution.

Potential roles of oxidative stress and insulin resistance in diisononyl phthalate induced dyslipidemia and hepatosteatosis in BALB/c mice

Exposure to plastic-derived endocrine disrupting chemicals (EDCs) such as phthalates have become a source of concern to human health. Phthalates are applied industrially as plasticizers in the production of various plastic products. They have been reported for the various forms of toxic responses in both human and animal studies. Diisononyl phthalate (DiNP) was recently used to replace di(2-ethylhexyl) phthalate (DEHP) due to some toxicity concerns. However, recent evidences suggest that DiNP may disrupt the endocrine system, alter lipid metabolism and induce hepatic steatosis. Hence, this work was designed to probe the potential impacts of DiNP on oxidative stress biomarkers and insulin resistance as a possible link to dyslipidemia and development of hepatic steatosis. To achieve these, twenty seven (27) male BALB/c mice were distributed into three (3) experimental groups of nine (9) mice each. Group I was the control while mice in groups II and III were exposed to 20 and 200 mg/kg body weight, (bw) DiNP respectively orally (per os, p.o.) for 28 days. Thereafter, plasma insulin, glucose, plasma lipid levels as well as insulin resistance (IR) index were determined. The effects of DiNP on hepatic biomarker of inflammation (tumor necrosis factor alpha, TNF-α), oxidative stress (malondialdehyde, MDA), antioxidants (glutathione peroxidase, reduced glutathione and catalase) were also investigated in addition to liver histopathology. Data obtained show that DiNP especially at 200 mg/kg bw significantly (p < 0.05) alter plasma glucose and lipid profile and induced IR. Other responses observed at this dose level include significant inflammation, oxidative stress and hepatic fatty degeneration (as shown in hematoxylin and eosin stained liver sections). Current findings suggest that insulin resistance and oxidative stress may influence DiNP-induced dyslipidemia and hepatic steatosis in mice.

Phylogenetic exploration and haemato-biochemical significance of Anaplasma marginale infection in water buffalo (Bubalus bubalis)

During 2017-2020, a total of 8352 buffalo blood samples were screened microscopically for Anaplsma species and 104 positive samples were found. Later on same samples were confirmed positive using genomic DNA PCR technique. For efficiency of PCR technique, a total of 335 blood samples were randomly chosen. Microscopy revealed Anaplasma species in erythrocytes of 1.19% (4 samples) of the total blood samples (n=335). Initially PCR assay was standardized targeting 16S rRNA for detection of genus Anaplasma with expected amplicon size 781 bp. Thereafter, msp1 β gene was targeted for species level identification of Anaplasma (Anaplasma marginale) with expected amplicon size 407 bp. A total of fourteen samples out of 335 samples (4.17%) found positive by PCR. Randomly, two confirmed positive samples were sent for bidirectional sequencing. The sequencing results, submitted in GenBank(MW269530, MW269531), further confirm the Anaplasma marginale infection in buffalo. The study show higher specificity and sensitivity of PCR test above blood smear examination. Erythron of infected animals showed significantly low level of mean Hb, PCV, RBC count, MCH, MCHC and high level of mean MCV, indicating regenerative hypochromic macrocytic anaemia. Infected animals had a significantly low mean level of total protein, albumin and globulin and significantly high level of phosphorus, total bilirubin, direct and indirect bilirubin. The current study provides indication of the association between A. marginale infection and probable liver damage or hepatic fatty degeneration. Nevertheless advanced studies are warranted to explain the precise pathophysiological mechanism of this association.

Ginsenoside CK ameliorates hepatic lipid accumulation via activating the LKB1/AMPK pathway in vitro and in vivo.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease with a complex etiology, and is considered as one of the main causes of hepatocellular carcinoma (HCC). The incidence of NAFLD has presented an increasing trend annually as a result of disequilibrium in the dietary structure. However, no specific treatment has been approved for clinical therapy in NAFLD. Ginsenoside CK has been investigated given its various pharmacological activities, but its effects against NAFLD and the underlying mechanism are still unclear. In this study, fructose was used to simulate hepatic fatty degeneration in vivo, while palmitic acid (PA) and oleic acid (OA) were applied to induce lipid accumulation in vitro. The level of lipid accumulation in hepatic tissue and HepG2 cells was evaluated by Oil Red O staining. Detection of serum and liver biomarkers, western blotting, and real-time qPCR were conducted to assess the degree of hepatic steatosis. Our results indicated that ginsenoside CK could decrease the lipid deposition in HepG2 cells, retard the increase of body weight of fructose-fed mice, alleviate the lipid accumulation in serum and hepatic tissue and improve the hepatic inflammation and injury. Mechanically, ginsenoside CK modulated the expression of factors correlated with lipid synthesis and metabolism in vitro and in vivo via activating the phosphorylation of LKB1 and AMPK. Compound C, an inhibitor of AMPK, partially abrogated the beneficial effects of ginsenoside CK in HepG2 cells. In summary, ginsenoside CK acts as a LKB1/AMPK agonist to regulate the lipid metabolism and interfere with the progression of NAFLD.

Potential mechanistic pathways underlying intestinal and hepatic effects of kefir in high-fructose-fed rats

Excess intake of fructose may contribute to the high prevalence of metabolic disorder. In this study, we investigated the effects of kefir supplementation on the intestine-liver-adipose tissue axis in metabolic disorder induced by high-fructose diet in rats to describe mechanistic action and potential therapeutic value of kefir. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administrated by gastric gavage once a day during the final six weeks. Kefir supplementation improved metabolic parameters, including plasma triglyceride and insulin levels; hepatic weight, triglyceride content and fatty degeneration; omental fat mass in fructose-fed rats. Kefir supplementation decreased the ratio of Firmicutes/Bacteroidetes in feces, as well as necrotic degeneration, expression levels of nuclear factor-kappa B (NF-κB), and inducible nitric oxide synthase (iNOS), but increased expression of tight-junction proteins occludin and claudin-1, in the ileum of the fructose-fed rats. Kefir treatment also reduced the mRNA levels of key lipogenic genes sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) together with a decline in expression of tumor necrosis factor-alpha (TNF-α), NF-κB, and glycosylated glycoprotein (CD68) in the liver. Moreover, kefir treatment improved insulin signaling at the level of insulin receptor substrate 1 (IRS-1) and phospho-endothelial nitric oxide synthase (peNOS) as well as fructose transporters (GLUT2 and GLUT5) in the liver, but not in the adipose tissue, of high-fructose-fed rats. Consequently, kefir supplementation suppresses hepatic lipogenesis and inflammatory status, but promotes insulin signaling, in association with a change of the fecal microbiota and attenuation of the intestinal permeability factors in high-fructose-fed rats. Thus, we propose that kefir has favorable effects on the hepatic and intestinal irregularities induced by fructose overconsumption.

Empagliflozin Alleviates Hepatic Steatosis by Activating the AMPK-TET2-Autophagy Pathway in vivo and in vitro.

Background: Metabolic associated fatty liver disease (MAFLD), characterized by hepatic lipid accumulation and fatty degeneration, is intertwined with obesity and type 2 diabetes mellitus (T2DM). Empagliflozin is a sodium-glucose cotransporter-2 inhibitor that effectively lowers blood glucose, but its effect on MAFLD and associated mechanisms are not fully understood. Methods: Eight-week-old db/db mice, an in vivo model, were administered empagliflozin or saline intragastrically. A hepatocyte steatosis model was established by inducing HL7702 cells with high glucose and palmitic acid and then treated with or without empagliflozin. The autophagy inhibitor (3-methyladenine, 3-MA) and AMP-activated protein kinase (AMPK) activator (AICAR)/inhibitor (Compound C) were used to determine the involvement of AMPK and autophagy in the regulation of lipid accumulation by empagliflozin. Ten-eleven translocation 2 (TET2) knockdown was achieved by siRNA transfection. Hepatic steatosis was evaluated by Oil Red O staining and triglyceride quantification. Immunohistochemistry, immunofluorescence, and western blot were performed to assess protein levels. Results: Empagliflozin alleviated liver steatosis in db/db mice and reduced triglyceride content and lipid accumulation in the hepatocyte steatosis model. Empagliflozin elevated autophagy, accompanied by an increase in p-AMPK and TET2. Both 3-MA and Compound C abolished the ability of empagliflozin to induce autophagy and reduce hepatic steatosis, while these effects could be recapitulated by AICAR treatment. TET2 knockdown resulted in autophagy inhibition and lipid accumulation despite empagliflozin treatment. Conclusion: Empagliflozin improves hepatic steatosis through the AMPK-TET2-autophagy pathway. The use of empagliflozin as a treatment for preventing and treating MAFLD in patients with T2DM warrants further study.

Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor 4/NFκB signaling: Comparison to metformin

AimsNon-alcoholic fatty liver disease (NAFLD) is a common liver disease. This study aimed to evaluate the role of exenatide compared with metformin in halting the progression of fatty liver stimulated by a high-fat diet (HiFD) in rats. Main methodsThirty male Wistar rats were allocated into 6 groups, 5 rats per each group. Group I: maintained on normal diet (normal group) for fourteen weeks. The other five groups were kept on HiFD throughout the experiment, HiFD was administered beside pharmacological treatments/or vehicle. Group II: (NAFLD control group), group III: received metformin (60 mg/kg/day, P.O.), group IV-VI: received exenatide (10, 20, and 40 μg/kg/day, S.C.) respectively for 7 weeks. At the end of the therapeutic period, fasting blood glucose was determined, and body weight was registered. Rats were sacrificed, and blood samples were taken to measure serum insulin, lipids, and liver enzymes. The liver index and homeostasis model of insulin resistance (HOMA-IR) index were calculated. Further, livers were dissected for histopathological examination and Western blot analysis. Key findingsNAFLD control group showed hyperglycemia, hyperinsulinemia, increased liver enzymes, hypertriglyceridemia, elevated hepatic lipid peroxides, and inflammatory mediators (interlukin 6, nuclear factor-κB, tumor necrosis factor-α and Toll-like receptor4) in addition to hepatic fatty degeneration. In a dose-dependent manner, exenatide significantly improved most of the above mentioned markers in comparsion with NAFLD at P≤0.05. SignificanceThe current results suggest that exenatide is equivalent to metformin in controlling insulin resistance, body weight gain, improving liver function, suppressing inflammation, and attenuating NAFLD progression in male rats.

LncRNA Gm12664\u2013001 ameliorates nonalcoholic fatty liver through modulating miR-295-5p and CAV1 expression

BackgroundOur study aims to investigate the mechanisms of lncRNA Gm12664–001 improved hepatic lipid accumulation-initiated NAFLD via regulating miR-295-5p and CAV1 in AML12 cells.MethodsThe animals were divided into normal control (NC) group and high fat diet (HFD) group (20 mice per group) for 8w. The steatotic liver was measured by hematoxylin eosin (HE) staining and kits. We performed systematical analyses on hepatic expression profiles of long noncoding RNAs (lncRNAs) and microRNAs in a high-fat diet (HFD)-induced steatotic animal model. The expression profile of targets was confirmed by bioinformatics analysis, luciferase assay, RT-PCR and western blot in AML12 cells.ResultsHFD treatment markedly observed hepatic fatty degeneration with primarily fat vacuoles, and increased TG level compared with control. According to microarray data, we found that transfection of Gm12664–001 siRNA (siRNA-118,306) obviously enhanced TG accumulation and repressed CAV1 in AML12 cells. Furthermore, the TG accumulation markedly increased by siRNA-mediated knockdown of CAV1 in AML12 cells. By bioinformatics prediction, AML12 cells were transfected of siRNA-118,306 obviously upregulated miR-295-5p. Transfection of miR-295-5p mimics significantly increased TG accumulation and obviously suppressed the target CAV1.ConclusionsThe results revealed that lncRNA Gm12664–001 attenuated hepatic lipid accumulation through negatively regulating miR-295-5p and enhancing CAV1 expression in AML12 cells.

Protective effect of kinsenoside on acute alcohol-induced liver injury in mice

Anoectochilus roxburghii (Wall.) Lindl., Orchidaceae, is a Chinese medicinal plant which can be effective for some diseases such as hepatitis, nephritis, pneumonia. Its active ingredient is kinsenoside. The mechanisms of kinsenoside on the liver-protective effect have not been fully explored until today. The present study was aimed to investigate the protective effect and mechanism of kinsenoside on acute alcoholic liver injury. The protected activity of kinsenoside (10, 20 and 40 mg/kg) were investigated on acute alcoholic liver injury in mice. Male C57BL/6 J mice were fed with non-fat feed for 30 days and oral administrated 14 ml/kg bw of ethanol (50%) on the 31st day. The activities of serum aspartate aminotransferase, serum alanine aminotransferase, triacylglyceride and very low density lipoprotein were determined in serum. The hepatic levels of oxidative stress as glutathione, malondialdehyde were measured in liver homogenates. The levels of cytochrome P450 2E1 (CYP2E1) were measured by immunohistochemistry. Furthermore, histopathological observations were carried out on the separated livers of mice. It was suggested that the trends of acute hepatic injury and fatty degeneration induced by alcohol were reduced in the ethanol group after kinsenoside treatment. Compared to ethanol groups, triacylglyceride, malondialdehyde, very low density lipoprotein, reduced glutathione, serum alanine aminotransferase and serum aspartate aminotransferase levels of kinsenoside (20, 40 mg/kg) groups were decreased (p < 0.05). Meanwhile kinsenoside significantly decreased the level of protein CYP2E1. In conclusion, kinsenoside enhances antioxidant capacity of mice and antagonizes alcohol-induced lipid metabolism disorders. Besides, kinsenoside inhibits alcohol-caused hepatocyte apoptosis, reduces oxidative stress, and relieves hepatocyte death, which may be a mechanism of kinsenoside in the treatment of alcoholic liver.

Pathological changes in two species of aquatic birds result from infection with some respiratory trematodes in Al-Hamar marsh / Thi-Qar province

Aquatic birds can be infected with internal parasites that may cause health problems . In the present study, Histopathological studies have been made to access the extent of damage caused by infection of some of aquatic birds with some species of Cyclocoelidae in Al-Hamar marsh / Thi-Qar province. Generally, the pathological changes that have certified in the lungs contain inflammation of lungs, change of color, increased in size and weight, irregular, hard in consistency, pale and yellow –white plaques on the surface, the parenchyma was edematous and purple to red in color, sometimes pale flabby with multiple focal grayish areas of consolidation, and occasionally with hemorrhagic foci. Fibrosis appeared as patched irregular areas with clear distinct borders with adjacent normal lung tissue. Other lungs showed significant edema with sub pleural patches of hemorrhage, which may occupy all lung lobes with proliferation it's lining epithelium cell, areas of pulmonary fibrosis, hyperplasia of bronchus lining epithelium cells, hemorrhage with sloughing parts of epithelium in the bronchus lumen, new blood vessels(angiogenesis). Conversely, The changes that have confirmed in the liver of some infected birds include, grossly; the livers have a nodular or granular appearance with dark lesions. When incised, these lesions usually contain clear, viscous, or pale yellow fluid. identical lesions also found inside hepatic parenchyma. Meanwhile, the histopathological changes include consolidation, rupture of hepatocytes. fibrinous of hepatic interlobular septi , Severe infiltration of inflammatory cells, hepatic fatty degeneration, necrosis of hepatic cells, hepatic cells vacuolation and degeneration.

Inhibitory Effects of Sodium Alginate on Hepatic Steatosis in Mice Induced by a Methionine- and Choline-deficient Diet.

Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice (n = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor-α and collagen 1α1, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.

THE EFFECT OF PRETREATMENT WITH TOLL-LIKE RECEPTOR 4 ANTAGONIST RESATORVID ON METHOTREXATE-INDUCED LIVER INJURY IN RATS: HISTOPATHOLOGICAL STUDY

Objective: This research aims to evaluate the histopathological changes after pretreatment with resatorvid against methotrexate induced-liver injury.Methods: 28 male albino-wistar rats divided into random 4 groups (7 rats in each). Control group: Rats left untreated. Vehicle pre-treated group: Rats were administered dimethyl sulfoxide (DMSO) followed by methotrexate (MTX). Methotrexate treated group: Rats left untreated then administered MTX. Resatorvid pre-treated group: Rats were administered resatorvid followed by MTX. 24 h after the end of treatment, the animals were sacrificed. Liver tissue samples dissected out immediately and fixed in 10% formalin. The traditional procedures (paraffin-embedded method) was used to prepare liver tissue for microscopic evaluation by none alcoholic fatty liver disease (NAFLD) Activity Score Components.Results: Liver tissue sections of MTX-treated group show moderate-to-severe steatosis of hepatic cells and micro- and macro- hepatocellular fatty degeneration and giant fatty cysts with chronic inflammatory cells infiltration. While liver tissue sections of the resatorvid pre-treated group show moderate hepatic cellular fatty degeneration, with a decreased number of fatty cysts chains and the inflammation disappeared.Conclusion: Resatorvid hepatoprotective effect against MTX-induced injury was promising throughout resolving the accompanying inflammation and partial restoring histopathological fatty alterations.

Investigation of functional hepatic tests in operated patients with obesity

Objective. To study up a connection between indices of the functional hepatic tests and the body mass index (BMI) in patients after the operation.&#x0D; Маterials and methods. In 59 оperated patients a BMI was calculated, as well as biochemical hepatic tests: activity of alaninaminotransferase (AlAT) in the blood serum, aspartataminotransferase (АsAТ), γ-glutamintransferase (γ-GТ) and a general bilirubin content. Basing on the BMI indices, all the patients were divided into three groups. Into Group I 30 patients were included with BMI 18.5 - 24.9 kg/m2, into Group II - 20 patients with excessive body mass, the BMI values 25.0 - 29.9 9 kg/m2, and into Group III - 9 patients with obesity, the BMI values more than 30 9 kg/m2. The blood serum activity of AlAT, AsAT, γ-GТ, alkaline phosphatase, indices of bilirubin, international normalized ratio and C-reactive protein were determined in accordnce to standard mrthods. In all the patients the data of hepatic function testing were analyzed before the operation and in 1, 3, 5 days after the operation.&#x0D; Results. In Groups I and II the values of АlAТ, АsAТ and γ-GТ were in borders of normal range. The changes were observed on the first and third postoperative day in Group III.&#x0D; Average activity (±SD) of the blood serum АlaТ and АsAТ in Group I have constituted (25.7 ± 9.8) and (24.9 ± 7.8) U/L (p &lt; 0.01), in Group II - (32.5 ± 9.1) and (25.2 ± 7.1) U/L (p &lt; 0.01), in Group III - (46.2 ± 13.5) and (31.9 ± 10.6) U/L (p &lt; 0.01).&#x0D; Conclusion. In high BMI in patients, who had hepatic fatty degeneration, a hepatic enzymes activity was raised significantly, comparing with patients who had not hepatic fatty degeneration. Raised activity of hepatic enzymes in the blood serum was connected with high BMI. That’s why a high rate of hepatic fatty degeneration is observed in patients with raised BMI.

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

Background/Aims: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Methods: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 10⁸ or 2.0 × 10¹⁰ vector genomes) or Control-AAV-EGFP (2.0 × 10⁸ vector genomes) was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD) for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. Results: LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS) axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. Conclusions: LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis.

Characteristics of WBN/Kob diabetic fatty rats supplemented with a fructose-rich diet as a metabolic syndrome model: response to a GLP-1 receptor agonist

The incidence of metabolic syndrome is rapidly increasing worldwide, and adequate animal models are crucial for studies on its pathogenesis and therapy. In the search of an adequate experimental model to simulate human metabolic syndrome, the present study was performed to examine the pharmacological response of WBN/Kob-Leprfa (WBKDF) rats supplemented with a fructose-rich diet (FRD) to liraglutide, a GLP-1 receptor agonist. Male WBKDF rats fed FRD at 7 weeks of age were divided into 3 groups, and administered liraglutide (75, 300 µg/kg subcutaneously) or saline (control group), once daily for 4 weeks. All rats in the control group became overweight, and developed hyperglycemia, hypertension and dyslipidemia as they aged. The rats given liraglutide exhibited a dose-dependent reduction in body weight, visceral fat content and food intake compared with control rats. In addition, liraglutide suppressed the development of hyperglycemia, hypertension and dyslipidemia. An intravenous glucose tolerance test revealed that liraglutide improved glucose tolerance, insulin secretion and insulin resistance. On histological examination, decreased hepatic fatty degeneration was observed in the liraglutide groups. The present study demonstrated that liraglutide protected against obesity, hyperglycemia, hypertension, dyslipidemia, and hepatic steatosis in WBKDF rats fed FRD, suggesting that WBKDF rats fed FRD may be a useful model to investigate the etiology of human metabolic syndrome.

Application of Indocyanine Green (ICG) Detection in Evaluating Early Prognosis in Patients with Fatty Liver Disease After Liver Transplantation.

BACKGROUND The relationship between the clearance rate of ICG (indocyanine green) and varying degrees of liver fatty degeneration remains to be explored. The value of ICG detection in the evaluation of early prognosis following hepatic transplantation has been rarely investigated. MATERIAL AND METHODS Clinical data of 106 patients undergoing liver transplantation were retrospectively analyzed. The severity of fatty degeneration of the resected liver specimens was assessed by pathological biopsy. All patients were assigned into one of three groups: A (no fatty degeneration), B (<20% hepatic fatty degeneration) or C (20-40% hepatic fatty degeneration). Multiple parameters were statistically compared among the three groups before, during, and after liver transplantation. RESULTS The results demonstrated that R15-D (15 minute detection rate of ICG in the donors) was positively correlated with R15-R (15 minute detection rate of ICG in the recipients). After liver transplantation, the peak values of ALT and total bilirubin (TB), and the R15-R and the rate of early allograft dysfunction (EAD) in group C were the highest among all three groups. However, the 3-month and 6-month survival rate of the grafts and the 1-year survival rate of the patients in group A were considerably lower compared to groups B and C. The area under the curve (AUC) of R15-R in predicting the EAD, 3-month survival rate and 6-month survival rate of the grafts and the 1-year survival rate of the patients was 0.956, 0.827, 0.867, and 0.794, respectively. CONCLUSIONS ICG detection rate can be used to predict the early prognosis of patients diagnosed with moderate liver fatty degeneration.

A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets

Radix salviae miltiorrhizae (Danshen in Chinese), a classic traditional Chinese medicine (TCM) herb, has been used for centuries to treat liver diseases. In this study, the preventive and curative potential of Danshen aqueous extract on acute/chronic alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) was studied. The in vivo results indicated that Danshen could alleviate hepatic inflammation, fatty degeneration, and haptic fibrogenesis in ALD and NAFLD models. In the aspect of mechanism of action, the significant reduction in MDA levels in both ALD and NAFLD models implies the decreased levels of oxidative stress by Danshen. However, Danshen treatment could not activate the internal enzymatic antioxidant system in ALD and NAFLD models. To further explore the hepatoprotective mechanism of Danshen, an in silico-based network pharmacology approach was employed in the present study. The pharmacological network analysis result revealed that six potential active ingredients such as tanshinone iia, salvianolic acid b, and Danshensu may contribute to the hepatoprotective effects of Danshen on ALD and NAFLD. The action mechanism may relate with regulating the intracellular molecular targets such as PPARα, CYP1A2, and MMP2 for regulation of lipid metabolism, antioxidant and anti-fibrogenesis by these potential active ingredients. Our studies suggest that the combination of network pharmacology strategy with in vivo experimental study may provide a forceful tool for exploring the mechanism of action of traditional Chinese medicine (TCM) herb and developing novel bioactive ingredients.

The Potency of Red Seaweed (Eucheuma cottonii) Extracts as Hepatoprotector on Lead Acetate-induced Hepatotoxicity in Mice.

Background:Lead is one of the most toxic metals, producing severe organ damage in animals and humans. Oxidative stress is reported to play an important role in lead acetate-induced liver injury.Aim:This study was carried out to investigate the role of ethanol extract of Eucheuma cottonii in protecting against lead acetate-induced hepatotoxicity in male mice.Materials and Methods:The sample used fifty male mice which were divided into five groups: negative control (mice were given daily with Aquadest); positive control (mice were given daily with lead acetate 20 mg/kg body weight (BW) orally once in a day for 21 days); and the treatment group (mice were given E. cottonii extracts 200 mg, 400 mg, and 800 mg/kg BW orally once in a day for 25 days, and on the 4th day, were given lead acetate 20 mg/kg BW 1 h after E. cottonii extract administration for 21 days). On day 25, the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured. The data of SGOT, SGPT, ALP, MDA, SOD, and GPx were analyzed with one-way ANOVA, followed by least significant difference test.Results:The results showed that oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT, SGPT, ALP, and MDA levels. Moreover, there was a significant decrease in SOD and GPx levels. Treatment with E. cottonii extracts of 800 mg/kg BW but not with 200 mg/kg BW and 400 mg/kg BW significantly (P < 0.05) decreased the elevated SGPT, SGOT, ALP, and MDA levels as compared to positive control group. Treatment with E. cottonii extracts of 800 mg/kg BW also showed a significant increase in SOD and GPx levels as compared to positive control group. Treating mice with lead acetate showed different histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and fatty degeneration whereas animals treated with lead acetate and E. cottonii extracts showed an improvement in these changes and the tissue appeared with normal structures.Conclusion:It can be concluded that E. cottonii extracts could be a potent natural product and can provide a promising hepatoprotective effect against lead acetate-induced hepatotoxicity in mice.SUMMARY In summary, Oxidative stress reported to play an important role in lead acetate induced liver injury. The lead acetate treatment significantly increased the SGOT, SGPT, ALP, MDA, and decreased the antioxidant enzymes (SOD and GPx) in liver. The inhibition of antioxidant enzymes will increase free radicals in liver tissues and might induce liver injury in mice. The presence of ethanol extract of Eucheuma cottonii with lead acetate showed protective effects as attenuating lead acetate against its liver toxicity, and this may be due to the activity of ethanol extract of Eucheuma cottonii as antioxidant. The antioxidant enzymes (SOD and GPx) were increased, and MDA, SGOT, SGPT, ALP were decreased after ethanol extract of Eucheuma cottonii administration. The enzymatic activities (SOD and GPx) and MDA in mice can be used as biomarkers of heavy metal toxicity such as lead acetate. Histopathological view of liver sections in the lead acetate treated group showed the liver damage, as compared to the negative control group. However, administration of ethanol extract of Eucheuma cottonii significantly improved the histopathological in liver of lead acetate-treated mice. From the results of this study we concluded that the ethanol extract of Eucheuma cottonii could be a potent natural product provide a promising protective effect against lead acetate induced liver toxicity in mice. Abbreviations Used: SGOT: Serum Glutamic Oxaloacetic Transaminase, SGPT: Serum Glutamic Pyruvate Transaminase, ALP: Alkaline Phosphatase, MDA: Malondialdehyde, SOD: Superoxide Dismutase, GPx: Glutathione Peroxidase.