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Background: Mining activities in South Kalimantan have been widely associated with the emergence of various health issues through heavy metal contamination in the water. Previous studies have demonstrated that the presence of heavy metals has an impact on physiological alterations inside many organs, notably the liver. Objective: The study aimed to determined the impact of liver damaged from heavy metal of lead (Pb), cadmium (Cd), and mercury (Hg), and the combination of the three in rat model. Methods: Our research used the true experiment laboratory method with a post-test group design. Male white rats (Rattus norvegicus), aged 2–6 months and weighing 250–300 grams, were assigned to the control group and the treatment group. Treatment groups were administered orally with water contaminated with heavy metals of Pb, Cd, and Hg orally for 28 days. The serum markers of liver damaged were then measured. Results: The levels of transaminase enzymes (AST and ALT) in the heavy metal-exposed group were increased compared to the control group. However, the increase was not statistically significant (p = 0.247; p = 0.349, respectively). The group exposed to Hg exhibited the highest levels of AST and ALT in comparison to the other groups. Conclusion: Heavy metal exposure tend to raise transaminase enzyme levels, indicating liver damage. Hg exhibited the greatest transaminase value increase of all heavy metals, indicating its highest potential for liver toxicity.

Simple Summary: The degree of liver damage after liver resection is generally assessed by serum ALT levels. Postoperative ALT levels may have a multifactorial cause correlated with the extent of resection, duration of surgery and of vascular clamping. Extensive and prolonged manipulation of the liver during open hepatectomy could also be correlated with hepatocyte injury. The aim of our study was to assess if a minimally invasive approach for liver resection, with less manipulation of the liver, may be associated with less transient hepatic damage and with consequent lower postoperative ALT levels than those detected after open hepatectomy. The results showed that liver resections performed using a minimally invasive approach were associated with significantly lower postoperative ALT values when compared with those performed by open approach. Moreover, the duration of hepatic pedicle clamping and multiple liver resections were independent predictors for high postoperative peak ALT levels on POD 1 and the minimally invasive approach showed a protective effect. Background: Postoperative serum ALT levels are one of the most frequently used marker to detect liver tissue damage following liver resection. The aim of this study was to evaluate if minimally invasive liver surgery (MILS) may result in less hepatic injury than open hepatectomy by assessing the differences of postoperative ALT levels. Methods: Patients who underwent MILS between 2009 and 2019 at our unit were included and compared with open liver resections. Median ALT levels was measured on postoperative day (POD) 1, 3 and 5. Postoperative peak transaminase (PPT) of ALT was determined on POD 1. The stabilized inverse probability treatment weighing (SIPTW) process was used to balance the two groups. A multivariable logistic regression analysis was used to analyze factors associated with high PPT. Results: After SIPTW, 292 MILS were compared with 159 open resections. Median ALT levels on POD 1, 3 and 5 were significantly higher in the open group than in the MILS group (301 vs. 187, p = 0.002; 180 vs. 121, p < 0.0001; 104 vs. 60, p < 0.0001; respectively). At the multivariable logistic regression analysis, MILS showed a protective effect for high PPT. Conclusions: MILS was associated with significantly lower postoperative ALT levels compared with open liver resections. MILS showed a protective effect for high PPT. [ABSTRACT FROM AUTHOR]

Crassocephalum rubens has several medicinal properties, making it effective against several ailments, including its local use for treating liver problems and breast cancer. The effect of crude extract of Crassocephalum rubens (CECR) against liver damage in 7, 12 - dimethylbenz[a]anthracene (DMBA)-induced mammary gland toxicity was investigated in female Wistar rats. Rats were divided into group of 5 (n = 8). Group 1 served as control. Animals in groups 2 to 4 were administered a single intraperitoneal dose of DMBA at 20 mg/kg. Groups 3 and 4 rats were thereafter treated with 250 mg/kg and 500 mg/kg b.w CECR, respectively, for 12 weeks. Rats in group 5 were given 500 mg/kg b.w. CECR only for 12 weeks. Effect of CECR on DMBA-induced anomalies was investigated by using various biochemical parameters, including liver marker enzymes, oxidative stress, and tissue histology and cell count. CECR ameliorated the hepatic damage accompanied with DMBA-induced mammary gland toxicity by mitigating the abnormal changes noted in the levels of the parameters investigated. This could be proved by a significant (p<0.05) reduction in the levels of serum transaminases, dehydrogenase (LDH), gamma-glutamyl transferase (GGT), lactate malondialdehyde (MDA) and estrogen, and a significant (p<0.05) increase in the levels of superoxide dismutase (SOD) and liver cell count when compared with DMBA-intoxicated rats. The CECR, mostly at 500 mg/kg. b.w. dose, could serve as an alternative therapy against liver inflammation and oxidative stress associated with DMBA-induced mammary gland toxicity. [ABSTRACT FROM AUTHOR]

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets. [ABSTRACT FROM AUTHOR]

Rats’ exposure to radiation led to an increased free radical from sub-toxic (24 µg/mol) to toxic concentration (120 µg/mol) in the system of rats. Free radical level exacerbate oxidative stress, thus, leading to hepatic damage, lipid profile and antioxidant alterations.This study investigated the effects of the bioactive constituent of n-butanol subfractions (subf) 1, 2, 3 and 4 of Adansonia digitata (A. digitata) and 1, 2 and 3 of Corchorus olitorius (C. olitorius) leaves on irradiation-induced hepatic damage, lipid profile and antioxidant alterations in system of Rats.A total of 54 rats (198 ± 5.00 g) were distributed into 9 groups of 6 each. Group I were fed with rat chow and distilled water only, all other groups were exposed to a single dose of 6 grey gamma irradiation, such that groups II, III, IV, V, VI, VII, VIII and IX were administered distilled water only, 1000 mg/kg body weight subfractions 1, 2, 3 and 4 of A. digitata, subfraction 1, 2 and 3 of C. olitorius respectively for 7 days.HPLC fingerprinting of the bioactive constituents of the subf of A. digitata and C. olitorius revealed the presence of catechin, eleagnin, quercetin, epicatechin, epigallocatechin, luteolin, astragalin, tocopherol, quercetin and catechin respectively. Irradiation significantly (p

Background: Cisplatin is a platinum-based chemotherapeutic drug utilized in the treatment of many solid-tissue cancers; it is associated with several organ toxicities. For ages, Phoenix Dactylifera, known as the '' large jujube '' or '' dà zǎo,'' in Chinese traditional medicine, has been employed for several medicinal applications. The present study assesses the role of Date Fruit Polysaccharides (DFP) in cisplatin-induced liver injury Method: Rats were intraperitoneally treated with a single therapeutic dose of cisplatin (5 mg/kg body weight) and then orally treated daily with or without 50/100 mg/kg body weight of DFP for 7 successive days.The salvaging effects of DFP were assessed on Cisplatin-induced hepatic damage, by investigating the hepatic function markers, oxidative stress, and pro-inflammatory biomarkers, with histopathological assessment of the liver morphology by hematoxylin/eosin stain. To elucidate the contents, functional groups, and antioxidative potentials of DFP, chromatographic, spectroscopic, and in vitro antioxidative assays were analysed. Results: Exposure to a single dose of cisplatin led to a considerable escalation in the tested hepatic function biomarkers (ALP and ALT), with an associated upsurge in levels/activities of malondialdehyde, cytokines, myeloperoxidase and a significant drop in the level of GSH (P < 0.05) in the liver as compared to the control. Moreover, there is also an obvious decline in antioxidant enzymes (catalase, SOD and GPx) activities. Contrarily, post-treatment with DFP significantly (P < 0.05) inhibited the heightened hepatic function markers, lipid peroxidation, inflammation, and oxidative stress dose-dependently. Analysis of chemical constituents, functional groups, and in vitro activities demonstrated important monosaccharides and antioxidative properties of DFP. Conclusion: This study shows the ability of DFP to serve as a probable salvaging agent in hepatic damage associated with cisplatin treatment.

Nazeer Hussain Khan,1,2 Enshe Jiang,2 Irfan Zia Qureshi1 1Human and Animal Physiology Laboratory, Department of Animal Sciences, Quaid-I-Azam University, Islamabad, 44000, Pakistan; 2Institute of Nursing and Health, Henan University, Kaifeng, Henan, 475004, People’s Republic of ChinaCorrespondence: Enshe Jiang; Irfan Zia Qureshi, Email esjiang@gmail.com; irfanziaqureshi@qau.edu.pkBackground: Fipronil (FPN) is a broad-spectrum phenylpyrazole insecticide, widely used in agriculture and veterinary medicine. Published research on FPN toxicity has established the fact that its inhalation or dermal exposure may lead to very serious clinical outcomes in non-target animals. In line to its exposure and toxicity related damage, FPN has been investigated in many invertebrates, however, its exposure-related noxiousness is less reported in higher animals.Objective: To assess the FPN-induced effects to agro-workers in the field, in the present study, we used physiological human surrogates, adult rhesus monkeys as models.Method: We exposed well habituated, chair restraint adult rhesus monkeys with a field spray concentration of FPN (0.3 mg/1 mL distilled water) through an inhalation route in the closed system. Animals were divided into control and treatment groups, each containing three animals. Inflammatory and hematological effects were determined by evaluating the kidney and liver biomarker enzymes; serum creatinine and alanine transaminase (ALT), aspartate transaminase (AST) levels respectively.Results: Our findings reveal that FPN treated monkeys show significantly increased levels of ALT (p = 0.000461), AST (p = 0.0681) and creatinine (p = 0.00656) as compared to the control group. Furthermore, significant differences of red blood cells (RBCs) (p = 0.0139) and white blood cells (WBCs) (p = 0.00642) were also observed in the treated and control group monkeys which reflect strong toxic effects on the blood cells.Conclusion: Our findings demonstrate that FPN exposure is very toxic to higher animals and causes severe damage to the liver and kidneys along with other clinical problems. The study highlights the effect and impact of passive inhalation of insecticides in intentionally carefree agro-workers and raises the concern of public awareness toward pesticides use.Keywords: rhesus monkeys (Macaca mulatta), fipronil, hepatic damage, nephrotoxic, pesticides use in Pakistan

AbstractContext Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored.Objective This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded.Materials and methods In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques.Results In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 μg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%).Conclusions These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 μg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine. [ABSTRACT FROM AUTHOR]

Polystyrene nanoplastics (PS-NPs) are environmental pollutants that induce oxidative stress (OS) in multiple organs particularly, liver. Sinensetin (SNS) is a naturally present flavones that shows diverse pharmaceutical properties i.e., anti-oxidant, anti-inflammatory and anti-apoptotic. Therefore, the present study was designed to evaluate the therapeutic role of SNS against PS-NPs induced hepatotoxicity. 48 rats were distributed into 4 groups i.e., control, PS-NPs (50 µgkg−1) treated, PS-NPs + SNS (50 µgkg−1 + 20 mgkg−1) co-treated and only SNS (20 mgkg−1) treated group. PS-NPs intoxication reduced the activities of catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidases (GPx) glutathione reductase (GSR) and glutathione (GSH) level, whereas increased the levels of ROS and MDA. Additionally, PS-NPs increased the levels of liver serum marker enzymes i.e., alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Moreover, the level of inflammatory makers such as nuclear factor-kappa B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) activity were increased following the PS-NPS exposure. The intoxication of PS-NPs elevated Caspase-3, Bax and Caspase-9 levels, while reducing the Bcl-2 level. Furthermore, the exposure of PS-NPs induced significant histopathological damages in hepatic tissue of rats. However, the supplementation of SNS considerably improved the PS-NPs induced damages as well as histological changes due to its hepatoprotective, anti-inflammatory, anti-apoptotic and anti-oxidant nature.

Background and purpose: Fatty liver disease and overcoming it is a health concern. This study aimed to investigate the effect of a period of high-intensity interval training (HIIT) and somatotropin injection on hepatocyte apoptosis markers and atherogenic index in mice with fatty liver disease. Materials and methods: In this basic experimental study, 21 male mice were randomly divided into three groups (n=7): control (C), exercise (HIIT), Exercise + somatotropin (H-GH). The HITT was performed for eight weeks/ five sessions a week. The speed was 25 meters per minute at the beginning which increased to 70 meters per minute at the end of week eight. The somatropin dosage was 1 mg/kg. Markers, including CK-18, paraoxonase, insulin resistance, ALT/AST ratio, and LDL/HDL were measured. Statistical analysis was carried out using One-way ANOVA and post hoc Tukey test. Results: CK18 values significantly decreased only in the HIIT group (P=0.01). Paraoxonase levels in both HIIT (P=0.00) and H-GH (P=0.01) groups significantly increased compared to the control group. Between groups changes of HOMA-IR index significantly reduced in the HIIT group (P=0.05) and slightly increased in the H-GH group but was not significant (P=0.36). The ratio of ALT/AST in both HIIT (P=0.02) and H-GH (P=0.03) groups significantly reduced. LDL/HDL ratio showed significant decrease only in the HIIT group (P=0.01). Conclusion: High-intensity interval training produced a more effective response in improving the markers of none alcoholic fatty liver disease than GH. Injection of growth hormone alone can have negative consequences on some indicators of the disease.

Background and purpose: Fatty liver disease and overcoming it is a health concern. This study aimed to investigate the effect of a period of high-intensity interval training (HIIT) and somatotropin injection on hepatocyte apoptosis markers and atherogenic index in mice with fatty liver disease. Materials and methods: In this basic experimental study, 21 male mice were randomly divided into three groups (n=7): control (C), exercise (HIIT), Exercise + somatotropin (H-GH). The HITT was performed for eight weeks/ five sessions a week. The speed was 25 meters per minute at the beginning which increased to 70 meters per minute at the end of week eight. The somatropin dosage was 1 mg/kg. Markers, including CK-18, paraoxonase, insulin resistance, ALT/AST ratio, and LDL/HDL were measured. Statistical analysis was carried out using One-way ANOVA and post hoc Tukey test. Results: CK18 values significantly decreased only in the HIIT group (P=0.01). Paraoxonase levels in both HIIT (P=0.00) and H-GH (P=0.01) groups significantly increased compared to the control group. Between groups changes of HOMA-IR index significantly reduced in the HIIT group (P=0.05) and slightly increased in the H-GH group but was not significant (P=0.36). The ratio of ALT/AST in both HIIT (P=0.02) and H-GH (P=0.03) groups significantly reduced. LDL/HDL ratio showed significant decrease only in the HIIT group (P=0.01). Conclusion: High-intensity interval training produced a more effective response in improving the markers of none alcoholic fatty liver disease than GH. Injection of growth hormone alone can have negative consequences on some indicators of the disease. [ABSTRACT FROM AUTHOR]

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Background: Benzodiazepines have been highly prescribed by physicians and have attracted public attention due to their high safety. These drugs have sedative, hypnotic, anti-anxiety, and anti-seizure properties. However, these drugs are also widely used for suicide. The present study was designed and implemented to determine the distribution of patients poisoned with benzodiazepines in terms of clinical and demographic characteristics. Methods: Investigation of poisoning with benzodiazepines in one year in the poisoning department of Loghman Medical Center in Tehran City, Iran, was carried out as a descriptive-prospective study. In this research, 458 poisoned patients were studied to collect data on their age, gender, drug dosage, type of drug, duration of hospitalization, blood analysis results, and mortality. Results: The majority of patients poisoned with benzodiazepines were women (62.2%). The mean age of people was 31.67 years. The most frequently used drugs were clonazepam and alprazolam. Other drugs used with benzodiazepines were propranolol, methadone, and acetaminophen. The death rate was 1.7%. The incidence of hypoglycemia and creatinine above 1.3 was 8.53% and 11.3%, respectively. Hyperglycemia was 10.6%. There were 11, 80, and 178 cases of elevated alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, respectively. Conclusion: Benzodiazepines have the potential to cause liver and kidney damage and changes in insulin secretion and blood sugar. This issue should be considered when dealing with a poisoned patient to prevent serious injuries.

Introduction: Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood. Objective: In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children. Methods: Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns. Results: Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein. Conclusion: Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection. [ABSTRACT FROM AUTHOR]

Obesity is a significant health concern affecting 13% of the world's population. It is often associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD), which can cause chronic inflammation in the liver and adipose tissue. Obese hepatocytes show increased lipid droplets and lipid peroxidation, which can lead to the progression of liver damage. Polyphenols have been shown to have the ability to reduce lipid peroxidation, thereby promoting hepatocyte health. Chia leaves, a by-product of chia seed production, are a natural source of bioactive antioxidant compounds, such as cinnamic acids and flavonoids, which have antioxidant and anti-inflammatory properties. In this study, chia leaves' ethanolic extracts of two seed phenotypes were tested on diet-induced obese mice to evaluate their therapeutic potential. Results show that the chia leaf extract positively affected insulin resistance and lipid peroxidation in the liver. In addition, the extract improved the HOMA-IR index compared to the obese control group, reducing the number and size of lipid droplets and lipid peroxidation. These results suggest that chia leaf extract may help treat insulin resistance and liver damage associated with MAFLD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetes mellitus is one of the most commonly arising endocrine conditions. The disorder gives rise to enduring damage to a number of body tissues and viscera as a result of related macrovascular and microvascular complications. In patients who are unable to maintain their nutritional status independently, medium-chain triglyceride (MCT) oil is frequently added as a supplement to parenteral nutrition. The aim of the present research is to establish whether MCT oil has a therapeutic influence on the hepatic damage occurring in male albino rats as a result of streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: 24 male albino rats were randomized into four cohorts, i.e., controls, STZ-diabetic, metformin-treated and MCT oil-treated. The rodents were fed a high-fat diet for 14 days; a low dose of intraperitoneal STZ was then administered in order to induce diabetes. The rats were subsequently treated for 4 weeks with metformin or MCT oil. Analysis included an appraisal of liver histology and biochemical indices, i.e., fasting blood glucose (FBG), hepatic enzymes and glutathione (GSH), the latter obtained from hepatic tissue homogenate. RESULTS: A rise in FBG and hepatic enzymes was observed, but in the STZ-diabetic cohort, hepatic GSH levels were diminished. Treatment with either metformin or MCT oil led to a decline in FBG and hepatic enzyme titers whereas GSH concentrations increased. Liver histology findings were notable amongst rodents within control, STZ-diabetic and metformin-treated groups. The majority of histological changes were resolved following therapy with MCT oil. CONCLUSIONS: The anti-diabetic and antioxidant characteristics of MCT oil have been substantiated by this work. MCT oil led to a reversal of the hepatic histological changes seen in STZ-induced diabetes in rats. [ABSTRACT FROM AUTHOR]

Skatole (3-methylindole, 3MI) is a natural-origin compound derived from plants, insects, and microbial metabolites in human intestines. Skatole has an anti-lipid peroxidation effect and is a biomarker for several diseases. However, its effect on hepatocyte lipid metabolism and lipotoxicity has not been elucidated. Hepatic lipotoxicity is induced by excess saturated free fatty acids in hyperlipidemia, which directly damages the hepatocytes. Lipotoxicity is involved in several metabolic diseases and hepatocytes, particularly affecting nonalcoholic fatty liver disease (NAFLD) progression. NAFLD is caused by the accumulation of fat by excessive free fatty acids (FFAs) in the blood and is accompanied by hepatic damage, such as endoplasmic reticulum (ER) stress, abnormal glucose and insulin metabolism, oxidative stress, and lipoapoptosis with lipid accumulation. Hepatic lipotoxicity causes multiple hepatic damages in NAFLD and has a directly effect on the progression from NAFLD to nonalcoholic steatohepatitis (NASH). This study confirmed that the natural compound skatole improves various damages to hepatocytes caused by lipotoxicity in hyperlipidemic conditions. To induce lipotoxicity, we exposed HepG2, SNU-449, and Huh7 cells to palmitic acid, a saturated fatty acid, and confirmed the protective effect of skatole. Skatole inhibited fat accumulation in the hepatocytes, reduced ER and oxidative stress, and recovered insulin resistance and glucose uptake. Importantly, skatole reduced lipoapoptosis by regulating caspase activity. In conclusion, skatole ameliorated multiple types of hepatocyte damage induced by lipotoxicity in the presence of excess free fatty acids. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. DON is mainly metabolized and detoxified by the liver. When the concentration of DON exceeds the metabolic capacity of the liver, it will trigger acute or chronic damage to the liver tissue. Previous studies demonstrated that bone marrow mesenchymal stem-cell-secreted exosomes (BMSC-exos) reduce liver injury. Therefore, we issue a hypothesis that in vitro-cultured rat BMSC-secreted exos could ameliorate liver damage after 2 mg/kg bw/day of DON exposure. In total, 144 lipids were identified in BMEC-exos, including high polyunsaturated fatty acid (PUFA) levels. BMSC-exos treatment alleviated liver pathological changes and decreased levels of alanine aminotransferase, aspartate aminotransferase, inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lipid peroxidation. Otherwise, low or high BMSC-exos treatment obviously changes DON-induced hepatic oxylipin patterns. According to the results from our correlation network analysis, Pearson correlation coefficient analysis, and hierarchical clustering analysis, the top 10% oxidized lipids can be classified into two categories: one that was positively correlated with copper–zinc superoxide dismutase (Cu/Zn SOD) and another that was positively correlated with liver injury indicators. Altogether, BMSC-exos administration maintained normal liver function and reduced oxidative damage in liver tissue. Moreover, it could also significantly change the oxylipin profiles under DON conditions. [ABSTRACT FROM AUTHOR]

IntroductionDengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood.ObjectiveIn this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children.MethodsHematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns.ResultsVascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein.ConclusionTaken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.

The first detection of Fascioloides (F.) magna in northeastern Bavaria in 2011 was presumably correlated to natural migration movements of free ranging wild ruminants originating from the neighboring Czech Republic, where high infection rates have been reported frequently. To gain more data on the continuing spreading and current occurrence of the giant liver fluke in surrounding regions, 700 livers of cloven-hoofed game originating from eleven different northeastern Bavarian counties were investigated for the presence of F. magna and accompanying liver parasites in the hunting season 2019–2020. Macroscopically altered liver tissue was further investigated by pathohistological and parasitological examination. F. magna was detected in 5.9% (38/640) of livers from red deer (0.7% < 1 year, 9.8% > 1 year; p < 0.05) whereas none of the investigated livers of wild boar, roe, and fallow deer was infected (n=60). Mild pathological alterations of the liver tissue were documented in 15, moderate in 14, and major in 9 of all F. magna-positive cases. Histologically, the fluke-specific pigment haematin, large trematode eggs, and periportal fibrosis were detected in the liver tissue of infected animals. In 9% of all investigated livers, parasitic stages of other parasites, i.e., Dicrocoelium dendriticum (6.0%), Fasciola hepatica (0.3%), Taenia spp. (1.7%), and Echinococcus multilocularis (1.0%), were found. According to the results of this study, F. magna is not restricted to formerly known affected regions of Upper Franconia, but is also present in the military training ground Grafenwöhr, Upper Palatinate, and the Bavarian Forest National Park, Lower Bavaria, with estimated prevalences of 3.6 and 16.4%, respectively, and thus seems to spread in suitable habitats in northeastern Bavaria. [ABSTRACT FROM AUTHOR]

Background: These days, food products industry involves the commercial production and addition of food colors, which comprises many food dyes, including caramel colors. 4-methylimidazole (4-MEI) is a component of various caramel-colored food products such as bakery, beer, soft drinks, coffee and sauces, which are consumed daily. The most common route of exposure is ingestion and liver is the organ of detoxification. The histomorphometric observations in liver after 4-MEI consumption have not been reported to the best of our knowledge and so the present study have been designed to evaluate the same. Methodology: Adult male Wistar albino rats weighing 150–200 g were procured for the study and divided into the control and experimental groups. The experimental animals were given 4-MEI orally by gavage tube at a dose of 250 mg/kg body weight daily for 1 month, while the control animals received distilled water. At the end of experiment, all the animals were euthanized under ether anesthesia by perfusion with Formal saline. Dissection and histopathological processing of liver was done for the examination. Results: The histomorphometric observations of the liver in experimental rats revealed a significant increase in sinusoidal width indicative of sinusoidal dilatation and congestion. There was a significant increase in the size of hepatocytes while a decrease in the size of their nuclei was noted, suggestive of ballooning degeneration. Conclusion: The findings in the present study strongly suggest hepatocellular damage caused by ingestion of 4-MEI found in caramel color dyes used routinely in the food industry.

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.

The article highlights a study to evaluate the effect of Ficus glumosa on phenylhydrazineinduced hemolytic anemia and hepatic damage in rats. It discusses that the leaves of F. glumosa contain important antioxidant(s) that could effectively reduce hemolytic anemia and hepatic damage, especially during phenylhydrazine-induced toxicity.

Obesity is a significant health concern affecting 13% of the world’s population. It is often associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD), which can cause chronic inflammation in the liver and adipose tissue. Obese hepatocytes show increased lipid droplets and lipid peroxidation, which can lead to the progression of liver damage. Polyphenols have been shown to have the ability to reduce lipid peroxidation, thereby promoting hepatocyte health. Chia leaves, a by-product of chia seed production, are a natural source of bioactive antioxidant compounds, such as cinnamic acids and flavonoids, which have antioxidant and anti-inflammatory properties. In this study, chia leaves’ ethanolic extracts of two seed phenotypes were tested on diet-induced obese mice to evaluate their therapeutic potential. Results show that the chia leaf extract positively affected insulin resistance and lipid peroxidation in the liver. In addition, the extract improved the HOMA-IR index compared to the obese control group, reducing the number and size of lipid droplets and lipid peroxidation. These results suggest that chia leaf extract may help treat insulin resistance and liver damage associated with MAFLD.

Objective(s): Along with increased intracranial pressure (ICP) and brain damage, brain edema is the most common cause of death in patients with hepatic encephalopathy. Curcumin can pass the blood-brain barrier and possesses anti-inflammatory and antioxidant properties. This study focuses on the curcumin protective effect on intrahepatic and extrahepatic damage in the brain. Materials and Methods: One hundred and forty-four male Albino N-Mary rats were randomly divided into 2 main groups: intrahepatic injury group and extrahepatic cholestasis group. In intra-hepatic injury group intrahepatic damage was induced by intraperitoneal (IP) injection of acetaminophen (500 mg/kg) [19] and included four subgroups: 1. Sham, 2. Acetaminophen (APAP), 3. Normal saline (Veh) which was used as curcumin solvent, and 4. Curcumin (CMN). In extrahepatic cholestasis group intrahepatic damage was caused by common bile duct litigation (BDL) and included four subgroups: 1. Sham, 2. BDL, 3. Vehicle (Veh), and 4. Curcumin (CMN). In both groups, 72 hr after induction of cholestasis, brain water content, blood-brain barrier permeability, serum ammonia, and histopathological indicators were examined and ICP was measured every 24 hr for three days.Results: The results showed that curcumin reduced brain edema, ICP, serum ammonia, and blood-brain barrier permeability after extrahepatic and intrahepatic damage. The maximum effect of curcumin on ICP was observed 72 hr after the injection.Conclusion: According to our findings, it seems that curcumin is an effective therapeutic intervention for treating encephalopathy caused by extrahepatic and intrahepatic damage.

Skatole (3-methylindole, 3MI) is a natural-origin compound derived from plants, insects, and microbial metabolites in human intestines. Skatole has an anti-lipid peroxidation effect and is a biomarker for several diseases. However, its effect on hepatocyte lipid metabolism and lipotoxicity has not been elucidated. Hepatic lipotoxicity is induced by excess saturated free fatty acids in hyperlipidemia, which directly damages the hepatocytes. Lipotoxicity is involved in several metabolic diseases and hepatocytes, particularly affecting nonalcoholic fatty liver disease (NAFLD) progression. NAFLD is caused by the accumulation of fat by excessive free fatty acids (FFAs) in the blood and is accompanied by hepatic damage, such as endoplasmic reticulum (ER) stress, abnormal glucose and insulin metabolism, oxidative stress, and lipoapoptosis with lipid accumulation. Hepatic lipotoxicity causes multiple hepatic damages in NAFLD and has a directly effect on the progression from NAFLD to nonalcoholic steatohepatitis (NASH). This study confirmed that the natural compound skatole improves various damages to hepatocytes caused by lipotoxicity in hyperlipidemic conditions. To induce lipotoxicity, we exposed HepG2, SNU-449, and Huh7 cells to palmitic acid, a saturated fatty acid, and confirmed the protective effect of skatole. Skatole inhibited fat accumulation in the hepatocytes, reduced ER and oxidative stress, and recovered insulin resistance and glucose uptake. Importantly, skatole reduced lipoapoptosis by regulating caspase activity. In conclusion, skatole ameliorated multiple types of hepatocyte damage induced by lipotoxicity in the presence of excess free fatty acids.

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. DON is mainly metabolized and detoxified by the liver. When the concentration of DON exceeds the metabolic capacity of the liver, it will trigger acute or chronic damage to the liver tissue. Previous studies demonstrated that bone marrow mesenchymal stem-cell-secreted exosomes (BMSC-exos) reduce liver injury. Therefore, we issue a hypothesis that in vitro-cultured rat BMSC-secreted exos could ameliorate liver damage after 2 mg/kg bw/day of DON exposure. In total, 144 lipids were identified in BMEC-exos, including high polyunsaturated fatty acid (PUFA) levels. BMSC-exos treatment alleviated liver pathological changes and decreased levels of alanine aminotransferase, aspartate aminotransferase, inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lipid peroxidation. Otherwise, low or high BMSC-exos treatment obviously changes DON-induced hepatic oxylipin patterns. According to the results from our correlation network analysis, Pearson correlation coefficient analysis, and hierarchical clustering analysis, the top 10% oxidized lipids can be classified into two categories: one that was positively correlated with copper–zinc superoxide dismutase (Cu/Zn SOD) and another that was positively correlated with liver injury indicators. Altogether, BMSC-exos administration maintained normal liver function and reduced oxidative damage in liver tissue. Moreover, it could also significantly change the oxylipin profiles under DON conditions.

Chemotherapy-induced liver injury has been found to be quite common in cancer patients undergoing chemotherapy. Being aware of chemotherapy-induced hepatotoxicity is important for avoiding errors in detecting liver metastases and for defining the most appropriate clinical management strategy. MRI imaging has proven to be a useful troubleshooting tool that helps overcome false negatives in tumor response imaging after chemotherapy due to liver parenchyma changes. The purpose of this review is, therefore, to describe the characteristics of magnetic resonance imaging of the broad spectrum of liver damage induced by systemic chemotherapeutic agents in order to avoid misdiagnoses of liver metastases and disease progression and to define the most appropriate clinical management strategy. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate morphological traits of hepatic parenchymal tissue repair in response to injury using the conventional technique (closure) and an innovation method (such as hemostatic medication swab packing and modified batching). The experimental study was carried out on laboratory rats of the Winzar breed using light microscopy, standard stains for micropreparations, and morphometry. Histopathologic examination of micropreparations stained by standard methods revealed pronounced dystrophic processes in hepatocytes located near the necrotic zone (albuminous and hydropic degeneration and chromatin fragmentation in the nuclei). Morphometric studies showed a significant decrease (p

The present study was designed to explore the hypolipidemic and hepatoprotective effects of Phyllanthus Niruri (PN) bioactive compound (-)-Epicatechin in D-galactosamine induced hepatitis in rats. Rats were distributed into normal controls (NC), (-)-epicatechin treated (Et), hepatitis control (Hc), hepatitis+ (-)-epicatechin (H+Et), hepatitis+silymarin treated (H+St). After 21 days of treatment, lipid peroxidation (MDA), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), high-density lipoprotein cholesterol (HDL), bilirubin (BL), urea (UR), creatinine (CR) are estimated in serum. In D-galactosamine-induced hepatitis rats, we observed increased levels of MDA, TC, TG, LDL, VLDL, BL, and decreased levels of HDL, UR, CR. However (-)-epicatechin supplementation normalized all the lipid metabolic profiles and also hepatic stress markers. Furthermore, histopathological examinations have also proved that (-)-epicatechin pre-treatment decreased the tissue damage in hepatitis conditions. This is the first reported data on the hypolipidemic activity of (-)-epicatechin. Our experimental findings indicate the potential benefits of (-) epicatechin in hepatitis conditions. [ABSTRACT FROM AUTHOR]

• Essential oils were extracted from fresh C. aurantium flowers through microwave-assisted hydrodistillation. • The detailed chemical composition analysis of C. aurantium flowers essential oil (CAEO) was performed by GC/MS-QP-2010 plus Ultra. • CAEO exhibits antioxidant, anti-inflammatory, and antiapoptotic effects, which protect against hepatocellular I/R-induced damage. The CAEO is an essential oil extracted from Citrus aurantium flowers, have been studied in relation to liver damage done by ischemia/reperfusion (I/R). CAEO was given orally for 2 weeks before ischemia, and rats were exposed to 1 h of ischemia accompanied by 5 h of reperfusion. Following I/R, hepatic lipid peroxidation, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels was increased, though hepatic glutathione content was reduced, CAEO has ameliorated these changes. I/R significantly improved serum levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), CAEO, however, has suppressed it. CAEO reduced the expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase, and TNF-a-associated proteins and improved a rise in heme oxygenase-1 (HO-1). CAEO inhibited the increase in COX-2, IL-6, and TNF-a mRNA expression, although the rise in HO-1 mRNA expression was boosted. CAEO suppressed nuclear factor-B nuclear localization in I/R rats. CAEO-treated rats had far less apoptotic cells than I/R rats. CAEO was found to have antioxidant, anti-inflammatory, and anti-apoptotic properties that defend against I/R-induced hepatocellular damage [ABSTRACT FROM AUTHOR]

The ever-increasing human population with attendant industrialization poses serious global health challenge. Cadmium (Cd) with other heavy metals contribute greatly to environmental pollutions and humans are daily exposed to them, leading to diverse ailments. We explored whether Hesperidin (HSP) could protect against hepatic damage and dyslipidemia in Wistar rats exposed to Cd. Forty wistar rats were randomly assigned into five groups (n = 8). Group 1 received 2 mL/kg body weight of normal saline; Group 2 received 100 mg/kg body weight of HSP while Group 3 received 5 mg/kg body weight of Cadmium Chloride (CdCl2) for 28 days. Group 4 received 100 mg/kg body weight of HSP and after 90 min, CdCl2 (5 mg/kg) body weight was administered for 28 days. Group 5 received 50 mg/kg body weight of HSP and after 90 min, CdCl2 (5 mg/kg) body weight was administered for 28 days. The serum lipid profiles, hepatic dysfunction and oxidative stress markers were determined using standard methods. Cd toxicity in rats prominently elevated serum activities of AST, ALT, ALP and levels of total bilirubin, direct bilirubin, cholesterol, LDL-C and malondialdehyde with decreased levels of HDL-C, triglycerides, superoxide dismutase, catalase, glutathione and body weights. The pre-treatment of HSP before Cd intoxication prevented the dysregulated activities of liver enzymes and levels of lipid profiles, enzymatic and non-enzymatic antioxidants and other biomarkers investigated, thus suggesting anti-hyperlipidemic and hepato-protective potentials. HSP may have great potentials for development of therapeutics that could enhance the management of dyslipidemia and liver disorders associated with heavy metal exposure.

Asari Radix et Rhizoma is a common drug for relieving exterior syndrome in clinics, but its toxicity limits its use. In this study, the mechanism of hepatic damage of Asari Radix et Rhizoma was studied by network pharmacology and metabolomics. The hepatic damage-related dataset, namely GSE54257 was downloaded from the GEO database. The Limma package was used to analyze the differentially expressed genes in the dataset GSE54257. Toxic components and target genes of Asari Radix et Rhizoma were screened by TCMSP, ECTM, and TOXNET. The hepatic damage target genes of Asari Radix et Rhizoma were obtained by mapping with the differentially expressed gene of GSE54257, and a PPI network was constructed. GO and KEGG enrichment analysis of target genes were performed, and a &quot;miRNA-target gene-signal pathway&quot; network was drawn with upstream miRNA information. Thirty rats were divided into a blank group, a high-dose Asari Radix et Rhizoma group, and a low-dose Asari Radix et Rhizoma group, which were administered once a day. After continuous administration for 28 days, liver function indexes and liver pathological changes were detected. Five liver tissue samples were randomly collected from the blank group and high-dose Asari Radix et Rhizoma group, and small molecule metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS). The orthogonal partial least squares-discriminant analysis(OPLS-DA) method was used to screen differential metabolites, and enrichment analysis, correlation analysis, and cluster analysis were conducted for differential metabolites. Finally, the MetaboAnalyst platform was used to conduct pathway enrichment analysis for differential metabolites. It was found that there were 14 toxic components in Asari Radix et Rhizoma, corresponding to 37 target genes, and 12 genes related to liver toxicity of Asari Radix et Rhizoma were obtained by mapping to differentially expressed genes of GSE54257. The animal test results showed that Asari Radix et Rhizoma could significantly increase the liver function index, reduce the activity of the free radical scavenging enzyme, change the liver oxidative stress level, and induce lipid peroxidation damage in rats. The results of untargeted metabolomics analysis showed that compared with the blank group, nine metabolites were up-regulated, and 16 metabolites were down-regulated in the liver tissue of the Asari Radix et Rhizoma group. These 25 metabolites had strong correlations and good clustering. Pathway enrichment analysis showed that these differential metabolites and the 12 hepatotoxic target genes of Asari Radix et Rhizoma were mainly involved in purine metabolism, as well as the biosynthesis and metabolism of valine, leucine, glycine, serine, and threonine. The study confirmed that the hepatica damage effect of Asari Radix et Rhizoma was the result of multi-component, multi-target, and multi-signaling pathways, and its mechanism may be related to inhibiting nucleotide synthesis and affecting protein metabolism.

Carbon tetrachloride (CCl4) is a toxic chemical that causes liver injury. CCl4 triggers endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR triggers autophagy to deal with the damage. The aim of this study was to investigate the effect of baicalein, derived from Scutellaria baicalensis, on CCl4-induced liver damage concerning ER stress and autophagy. Two groups of Wistar albino rats (n = 7/groups) were treated with 0.2 ml/kg CCl4 for 10 days with and without baicalein. Histological and transmission electron microscopy (TEM) analysis, autophagy, and ER stress markers measurements were carried out to evaluate the effect of baicalein. Histological examinations showed that baicalein reduced liver damage. TEM analysis indicated that baicalein inhibited ER stress and triggered autophagy. CCl4-induced elevation of C/EBP homologous protein (CHOP), glucose-regulating protein 78 (GRP78), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK), and active/spliced form of X-box-binding protein 1 (XBP1s) ER stress markers were decreased by baicalein. Baicalein also increased the autophagy-related 5 (ATG5), Beclin1, and Microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine-conjugated form (LC3-II) autophagy marker levels. In conclusion, baicalein reduced the CCl4-induced liver damage by inhibiting ER stress and the trigger of autophagy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a serious chronic disease in which the oxidant-antioxidant balance is impaired, causing many complications, including hepatopathy. In this study, the effects of short-term and low-dose N-acetylcysteine (NAC) administration on the biochemical, proinflammatory, and oxidative stress parameters in the liver tissue of diabetic rats were investigated. Twenty-four adult male Wistar albino rats weighing approximately 250–300 g were divided into 4 groups (n = 6): Control, Streptozotosin (STZ)-induced diabetes (DM), NAC treatment (60 mg/kg), and STZ-induced diabetes treated with NAC (DM+NAC; 60 mg/kg). NAC treatment was administered intraperitoneally as a single daily dose for 7 days. At the end of the experiment (3 weeks), blood and liver samples were collected for biochemical parameter analysis. Lipid peroxidation, antioxidant parameters, and nitric oxide (NOx) levels were determined by spectrophotometric method. Tissue inflammation parameters were evaluated by ELISA. Lipid peroxidation, proinflammatory cytokines, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values increased significantly with diabetes. NAC treatment significantly decreased serum ALT and AST levels and proinflammatory cytokines in the diabetic group. Liver glutathione (GSH) and NOx levels increased significantly in the DM+NAC group (p < 0.05). While NAC treatment reduced lipid peroxidation in the liver, it improved the inflammatory response and antioxidant status. The beneficial effect of NAC treatment may be due to its antioxidant activity and the resulting increased level of GSH. The results show that low-dose and short-term NAC treatment had a positive effect on oxidative damage and inflammation in liver tissue. NAC can be used as a potential antioxidant in diabetes to prevent hepatopathy. [ABSTRACT FROM AUTHOR]

Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) has been used as a replacement in some commercial flame-retardant mixtures. It is widely used in industrial products, so the probability of human exposure to TBPH is high. Yet, little is known about how it is metabolized or its toxicity. To this end, we investigated what effect oral exposure of Balb/c mice to TBPH at concentrations of 200 mg kg−1 had on hepatic damage. Staining results showed liver injury in the mice exposed to TBPH. Oxidative stress markers and endoplasmic reticulum stress associated proteins were altered in the TBPH exposed mice, and these changes could be attenuated by administration of curcumin at 25 mg kg−1. Overall, TBPH induces hepatic damage via increasing oxidative stress, and curcumin plays a protective role in alleviating the TBPH-mediated histopathological alterations in the liver. [ABSTRACT FROM AUTHOR]

Objective(s): Along with increased intracranial pressure (ICP) and brain damage, brain edema is the most common cause of death in patients with hepatic encephalopathy. Curcumin can pass the blood-brain barrier and possesses anti-inflammatory and anti-oxidant properties. This study focuses on the curcumin protective effect on intrahepatic and extrahepatic damage in the brain. Materials and Methods: One hundred and forty-four male Albino N-Mary rats were randomly divided into 2 main groups: intrahepatic injury group and extrahepatic cholestasis group. In intra-hepatic injury group intrahepatic damage was induced by intraperitoneal (IP) injection of acetaminophen (500 mg/kg) [19] and included four subgroups: 1. Sham, 2. Acetaminophen (APAP), 3. Normal saline (Veh) which was used as curcumin solvent, and 4. Curcumin (CMN). In extrahepatic cholestasis group intrahepatic damage was caused by common bile duct litigation (BDL) and included four subgroups: 1. Sham, 2. BDL, 3. Vehicle (Veh), and 4. Curcumin (CMN). In both groups, 72 hr after induction of cholestasis, brain water content, blood-brain barrier permeability, serum ammonia, and histopathological indicators were examined and ICP was measured every 24 hr for three days. Results: The results showed that curcumin reduced brain edema, ICP, serum ammonia, and blood-brain barrier permeability after extrahepatic and intrahepatic damage. The maximum effect of curcumin on ICP was observed 72 hr after the injection. Conclusion: According to our findings, it seems that curcumin is an effective therapeutic intervention for treating encephalopathy caused by extrahepatic and intrahepatic damage. [ABSTRACT FROM AUTHOR]

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Polystyrene nanoplastics (PS-NPs) are environmental pollutants that induce oxidative stress (OS) in multiple organs particularly, liver. Sinensetin (SNS) is a naturally present flavones that shows diverse pharmaceutical properties i.e., anti-oxidant, anti-inflammatory and anti-apoptotic. Therefore, the present study was designed to evaluate the therapeutic role of SNS against PS-NPs induced hepatotoxicity. 48 rats were distributed into 4 groups i.e., control, PS-NPs (50 µgkg−1) treated, PS-NPs + SNS (50 µgkg−1 + 20 mgkg−1) co-treated and only SNS (20 mgkg−1) treated group. PS-NPs intoxication reduced the activities of catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidases (GPx) glutathione reductase (GSR) and glutathione (GSH) level, whereas increased the levels of ROS and MDA. Additionally, PS-NPs increased the levels of liver serum marker enzymes i.e., alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Moreover, the level of inflammatory makers such as nuclear factor-kappa B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) activity were increased following the PS-NPS exposure. The intoxication of PS-NPs elevated Caspase-3, Bax and Caspase-9 levels, while reducing the Bcl-2 level. Furthermore, the exposure of PS-NPs induced significant histopathological damages in hepatic tissue of rats. However, the supplementation of SNS considerably improved the PS-NPs induced damages as well as histological changes due to its hepatoprotective, anti-inflammatory, anti-apoptotic and anti-oxidant nature. [ABSTRACT FROM AUTHOR]

Oat (Avena sativa) bran, a by-product during oat grain processing, is a excellent source of fibre, vitamins and phytochemicals. The health benefits of dietary fibre have long been established. In the present study, the antioxidant and hepatoprotective effects of oat bran extracts were investigated. The extracts showed strong 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), hydroxyl, superoxide radicals scavenging and reducing power activities in vitro. In addition, the extracts (50 mg/kg mouse) significantly reduced the levels of malondialdehyde and hepatic damage marker enzymes (aspartate transaminase and alanine transaminase), proinflammatory cytokines as well as elevated SOD, CAT, and GPx enzymes expressions in LPS-treated (1 mg/kg body weight) BALB/c mice. Therefore, the present study strongly suggests that both oat bran extracts could be excellent raw materials for manufacturing functional food due to its protective effect on hepatic liver damage and excellent antioxidant activity.

Introduction Neuropsychiatric drugs account for 16% of drugs that can lead to hepatotoxicity and psychiatric patients can have multiple comorbidities that can increase the incidence of liver disorders such as alcoholism, drug abuse and polymedication. The continuous use of atypical antipsychotic drugs (AAD) has raised questions over their tolerability over endocrine, metabolic and cardiovascular systems. They are also associated with mild elevation of aminotransferases and occasionally cause idiosyncratic liver injury with varying phenotypes. Hepatotoxicity is defined based on biological parameters such as elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT or clinical abnormalities (jaundice and hepatitis). Objectives This work reviewed the current available evidence on the hepatic damage produced by AAD. Methods Non-systematic review of the literature with selection of scientific articles published in the past 10 years; by searching Pubmed and Medscape databases using the combination of MeSH descriptors. The following MeSH terms were used: atypical antipsychotic drugs; hepatotoxicity; hepatic; Olanzapine; Clozapine; Risperidone; Aripiprazol; Paliperidone. Results Atypical Antipsychotic Drugs are generally well tolerated and hepatic alterations are in general very low or rare. The cases published were observed with Clozapine, Olanzapine and Risperidone. Atypical Antipsychotic drugs have a better profile than Chlorpromazine. Conclusions In conclusion, the hepatic injury generally occurs within the first weeks of treatment and is usually reversible with drug withdrawal. Hepatic check-ups may be relevant, especially in the beginning of treatment. Disclosure No significant relationships.

The present study investigated the combinatorial effect of gallic acid and catechin (GC) on some biochemical and inflammatory parameters in CCl4-mediated hepatic damage to rats. Male Wistar rats were distributed equally into five groups. Group A (control) received distilled water orally and olive oil intraperitoneally (ip), group B rats were intoxicated with CCl4 {1.25 ml/kg in olive oil, ip) only, while Groups C, D and E were induced with CCl4, thereafter they were administered 50 mg/kg body weight of silymarin, combined dose of gallic acid and catechin (50 and 100 mg/kg bw, 1:1) for 7 days respectively. After 7 days of treatment, the rats were sacrificed, and the fasting blood sample was collected by cardiac puncture for biochemical analyses. Findings from our results show that there were significant increases (p ˂ 0.05) in serum hepatic enzyme markers (ALT, AST, ALP, and GGT activities), bilirubin, albumin, and malondialdehyde (MDA) concentrations, but a significant decrease in GSH, SOD and CAT activities. It was also observed that the antioxidant genes coding for SOD and CAT were down-regulated or suppressed, while the inflammatory cytokines (IL-1B, IL-6, COX 2, and TNF α) were activated in rats intoxicated with CCl4 when compared to the control group. Administration of the combined dose of GC and silymarin drug attenuated the toxic insult of CCl4 at the biochemical and molecular levels. Our findings confirm that a combination of gallic acid and catechin may have exhibited a synergistic hepatoprotective activity against CCl4 induced liver damage.

Objectives Improper usage of acetaminophen (APAP) leads to morbidity and also mortality secondary to liver damage. Ginseng could suppress APAP-induced hepatotoxicity and ginsenoside Rg3 is a kind of major component in ginseng against liver damage. Herein, we intended to estimate the beneficial function and molecular mechanism of Rg3 on APAP-caused hepatotoxicity and identified hepatoprotection. Methods A total of 50 C57BL/6J mice were divided into five random groups, and each contains 10 mice as the control, acetaminophen (350 mg/kg) and Rg3 (5, 10 and 20 mg/kg) + acetaminophen (350 mg/kg) groups. These mice were intragastric administration a single dose of acetaminophen by oral treatment behind pre-administered with several doses of ginsenoside Rg3 for six hours. Key findings According to our data, the injection of APAP (350 mg/kg) enhanced the basal levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactic dehydrogenase. However, these abnormal added were alleviated by Rg3. Moreover, Rg3 treatment obviously relieved APAP-caused inflammation and oxidant in liver tissues. The depletion of glutathione, glutathione peroxidase, total antioxidant capacity and generation of malondialdehyde induced by APAP treatment were reduced by Rg3. By H&E staining, Rg3 effectively reduced APAP-caused apoptosis and inflammatory infiltration. Moreover, Rg3 attenuated APAP-caused hepatic damage in part by regulating the pro-inflammatory and anti-inflammatory cytokines. Moreover, we found that Rg3 could bind to NLRP3 suggesting the anti-inflammatory effects of Rg3 by molecular docking study. Conclusions In summary, Rg3 showed hepatic protective function in APAP-induced hepatotoxicity as evidenced by a reduction of the oxidant and the inflammatory reply, relieve of hepatocellular damage, showing potential in Rg3 as a potential therapeutic medicine to prevent hepatic injury. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced liver injury has been found to be quite common in cancer patients undergoing chemotherapy. Being aware of chemotherapy-induced hepatotoxicity is important for avoiding errors in detecting liver metastases and for defining the most appropriate clinical management strategy. MRI imaging has proven to be a useful troubleshooting tool that helps overcome false negatives in tumor response imaging after chemotherapy due to liver parenchyma changes. The purpose of this review is, therefore, to describe the characteristics of magnetic resonance imaging of the broad spectrum of liver damage induced by systemic chemotherapeutic agents in order to avoid misdiagnoses of liver metastases and disease progression and to define the most appropriate clinical management strategy.

The current study aimed to explore the protective roles of ginseng against dexamethasone liver devastating effects. Sixty male rats were equally allocated into six groups; G1: control, G2: ginseng aqueous extract (200 mg/kg B.W. orally /4 weeks), G3: dexamethasone (1mg/kg B.W. i.p/one week then decapitated), G4: dexamethasonewithdrawal group (1mg/kg B.W. i.p/one week and decapitated at the end of experiment), G5: dexamethasone ginseng treated group (injected with dexamethasone/one week then treated with ginseng/other 3weeks), and G6: ginseng-dexamethasone-ginseng group (received ginseng/two weeks followed by dexamethasone/one week then ginseng/another week). Dexamethasone significantly increased serum liver enzymatic activities alongside with mild to moderate hepatic vacuolation, and periportal mononuclear infiltration suggesting liver damage. The level of hepatic malondialdehyde (MDA) was elevated markedly with subsequent decline in the reduced glutathione concentration following challenged with dexamethasone. Moreover, the hepatic expression of thioredoxin mRNA transcript was down-regulated while BCL2-associated X protein (Bax) mRNA transcript was up-regulated providing imbalance in antioxidant and apoptosis pathway. Ginseng treatment ameliorated the damaged effects of dexamethasone on the liver as indicated by attenuation of elevated liver enzymatic activities, augmentation the reduced glutathione level, up-regulation thioredoxin mRNA transcription along with down-regulation of Bax mRNA expression in liver tissue. Conclusively, ginseng exerted a protective action on dexamethasone hepatic side effects through anti-apoptotic and antioxidant properties. [ABSTRACT FROM AUTHOR]

Hepatic damage has been recognized as one of the major complications in diabetes mellitus. Our previous studies have verified that grape seed procyanidin B2 (GSPB2) played a protective effect on hepatic damage of diabetes. We used isobaric tag for relative and absolute quantitation proteomics here to identify the alterant mitochondrial protein profile in diabetic liver and to seek the protective targets of GSPB2. Proteomics found that 171 proteins were upregulated or downregulated in the liver mitochondria of diabetic group compared to the control group. Of these proteins, 61 were normalized after GSPB2 treatment. These back‐regulated proteins are involved in the process of fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and apoptosis. Some differentially expressed proteins were confirmed by western blotting. Our study might help to better understand the mechanism of mitochondrial dysfunction in diabetic liver damage, and provide novel targets for estimating the protective effects of GSPB2. Practical applications: Grape seed procyanidin B2 (GSPB2), a polyphenolic component found in red wine and grapes, has beneficial effects such as antioxidative stress, antiapoptosis, and cardiovascular protection. We used proteomics here to identify the differentially expressed mitochondrial proteins in diabetic liver after GSPB2 treatment and to seek the protective targets of GSPB2. We found that the differentially expressed proteins were involved in carbon metabolism, oxidative phosphorylation, fatty acid metabolism, citrate cycle, oxidative stress, and apoptosis. These proteins may play a key role in diabetic hepatic damage as functional proteins. Targeting these proteins including apply of GSPB2 could potentially lead to an effective treatment in the diabetic hepatic disease. [ABSTRACT FROM AUTHOR]

Heliotropium indicum Linn is a leafy vegetable that has been used in Bangladeshi ethnomedicinal practices. The attenuation effect of H. indicum supplementation was evaluated in high carbohydrate high‐fat (HCHF) diet‐induced obesity and associated disorders in 8‐weeks‐old female Wister rats. H. indicum significantly (p <.05) prevented weight gain and improved glucose intolerance in obese rats. It also significantly (p <.05) ameliorated lipid parameters in HCHF diet fed rats preventing hypercholesterolemia and hypertriglyceridemia, resulting in improved the artherogenic index (AI). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were brought to normal by H. indicum. It significantly elevated superoxide dismutase (SOD) and catalase (CAT) activities as well as increased reduced glutathione (GSH) concentration in liver. The intense liver fat deposition was seen in HCHF fed rats which were relatively low in H. indicum fed rats. Therefore, H. indicum has the ability to prevent obesity and associated metabolic disorders. Practical applications: Obesity and associated metabolic disorders are the most common threats to public health. Modern lifestyle and food habits are the main causes behind this malice, and the introduction of functional foods in daily diet is proved to be highly beneficial. Results of this study demonstrated that H. indicum can effectively attenuate obesity and its associated metabolic complications. Therefore, the current study has the merits to promote scientific knowledge of the dietary application of H. indicum as a functional food among the community. [ABSTRACT FROM AUTHOR]