Liver Biomarkers Research Articles

Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment.

Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites, and exhibit altered toxicity compared with their parent compounds. This article describes a 2-chamber liver-organ coculture model in a higher-throughput 96-well format for the determination of toxicity on target tissues in the presence of physiologically relevant human liver metabolism. This 2-chamber system is a hydrogel formed within each well consisting of a central well (target tissue) and an outer ring-shaped trough (human liver tissue). The target tissue chamber can be configured to accommodate a three-dimensional (3D) spheroid-shaped microtissue, or a 2-dimensional (2D) cell monolayer. Culture medium and compounds freely diffuse between the 2 chambers. Human-differentiated HepaRG liver cells are used to form the 3D human liver microtissues, which displayed robust protein expression of liver biomarkers (albumin, asialoglycoprotein receptor, Phase I cytochrome P450 [CYP3A4] enzyme, multidrug resistance-associated protein 2 transporter, and glycogen), and exhibited Phase I/II enzyme activities over the course of 17 days. Histological and ultrastructural analyses confirmed that the HepaRG microtissues presented a differentiated hepatocyte phenotype, including abundant mitochondria, endoplasmic reticulum, and bile canaliculi. Liver microtissue zonation characteristics could be easily modulated by maturation in different media supplements. Furthermore, our proof-of-concept study demonstrated the efficacy of this coculture model in evaluating testosterone-mediated androgen receptor responses in the presence of human liver metabolism. This liver-organ coculture system provides a practical, higher-throughput testing platform for metabolism-dependent bioactivity assessment of drugs/chemicals to better recapitulate the biological effects and potential toxicity of human exposures.

Liver and mucous secretion enzymatic biomarkers of Eobania vermiculata treated with some newly synthesized acrylamide derivatives

Abstract Background Acrylamide derivatives have a potential biological activity as well as acting as precursors in many organic syntheses. Moreover, acrylamides and their derivatives cause convulsions and diffused damage to different sections of the nervous system of infected animals. Novel copper and zinc chelates originated from (E)-3-(4-bromophenyl)-2-cyanoacrylamide (L1), and (E)-2-cyano-3-(4-nitrophenyl)acrylamide (L2) were prepared, and their chemical skeletons were identified by infrared and mass spectra. The obtained compounds were screened in vitro against the brown garden snail, Eobania vermiculata using the contact method along 72 h. Stock solutions of tested compounds were prepared utilizing distilled water and DMSO mixture, and four concentrations of each compound were prepared (50, 150, 250 and 350 ppm). Eobania vermiculata snails were treated with LC50 concentrations of prepared compounds for 3 days, and live snails were used to estimate the level of some liver and mucous secretion enzymatic biomarkers: transaminases enzymes (Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)), Total Protein content (TP), Acid Phosphatases (ACP) and Alkaline Phosphatase (ALP). Results The results demonstrated that the examined compounds have a relatively toxic effect toward the screened species. Zinc complexes displayed a higher toxicity than copper ones. The results authenticated considerable high effects of the synthesized compounds on investigated enzymes. Conclusions The promising effects of Cu(II), Zn(II) complexes (1, 2) on stimulating the mucous secretion of tested snails are clear through the elevated levels of ALP and ACP enzymes of treated snails. The enhancement or reduction of AST, ALT level and TP content of treated snails demonstrated the effects of prepared compounds on liver functions of these species.

Evaluation of the Effect of Cichorium intybus L. on the Liver Enzymes in Burn Patients: A Randomized Double-Blind Clinical Trial.

Burn injuries are considered an important public health problem in the world. Burns are considered the fourth most common kind of trauma in the world, after traffic accidents, falls, and interpersonal violence. Various biochemical agents are involved in the burn healing process such as cytokines (such as IL-6 and TNF-α), antioxidants, and liver and kidney damage biomarkers. Cichorium intybus L. and milk thistle extracts showed a wide range of pharmacological activities such as significant antimicrobial effect and antioxidant activity, as well as anti-inflammatory, antidiabetic, antiproliferative, antiprotozoal, and hepatoprotective effect. Also, these two herbs possess blood-cleansing, detoxifying, laxative, and invigorating activities. Some research confirmed that the preparations of the extract are very suitable for the treatment of nonalcoholic fatty liver disease. This is a double-blind randomized controlled clinical trial. Patients with 2nd and 3rd degree burns have been selected to participate in the study according to the inclusion criteria. A total of 60 patients were selected and divided into intervention and control groups (30 patients in each group). Patients in the intervention group received chicory seed syrup 10 cc three times a day and 1 placebo capsule, and those in the control group received placebo syrup (10 cc three times a day) and one Livergol (140 mg of silymarin in each capsule) capsule. Lab data such as liver function tests, albumin, creatinine, BUN, and hemoglobin were checked every 3 days and 1 week after discharge. The treatment lasted for 4 weeks. According to the results of the study, although the average of liver enzymes at the end of the study does not show a significant difference between the two groups, the level of liver enzymes in each group decreased on the 15th day of the study compared to the first day. This trial is registered with IRCT20180609040016N1.

Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. The present cross-sectional study included a cohort of 177 young adults aged 18-25years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Toxicological Evaluation of Crude Musa sapientum L (Banana) Methanol leaves Extract of in wistar albino rats

Abstract Introduction: Musa sapientum, L commonly known as banana, has been traditionally used for both nutritional and medicinal purposes across various cultures. Different parts of the plant are believed to possess therapeutic properties. Aim: This study aims to assess the toxicological profile of Musa sapientum L. methanol leaf extract (MSMLE) in Wistar albino rats to evaluate its safety and potential medicinal benefits. It focuses on the phytochemical constituents, determination of the lethal dose 50 (LD50), and subchronic effects on liver and kidney biomarkers, as well as hematological parameters. Materials and Methods: Phytochemical constituents of MSMLE were determined using standard methods. The LD50 was determined following OECD guidelines by administering fixed doses to groups of rats. For the subchronic study, rats were divided into five groups: a control group receiving distilled water (2 mg/kg) and four groups receiving escalating doses of MSMLE (150, 300, 600, and 1200 mg/kg) orally for 28 days. Graph Pad Instat Version 3.0 was used for data analysis. Results: Phytochemical screening confirmed the presence of alkaloids, steroids, flavonoids, tannins, and saponins in MSMLE. The LD50 was found to be greater than 3000 mg/kg, indicating low acute toxicity. Significant decreases (P&lt;0.05) in alkaline phosphatase (ALP), albumin (ALB), and alanine transaminase (ALT) were observed only in the group receiving the highest dose (1200 mg/kg) compared to the control. Kidney function biomarkers also showed significant decreases (P&lt;0.05) in the high-dose group. Hematological parameters, including red blood cells (RBC), white blood cells (WBC), hemoglobin (HGB), and neutrophils, decreased significantly (P&lt;0.05), while mean corpuscular volume (MCV) and lymphocytes showed a significant increase. Conclusion: The study concludes that MSMLE demonstrates low acute toxicity with an LD50 above 3000 mg/kg. However, subchronic administration at the highest dose (1200 mg/kg) resulted in significant changes in liver and kidney biomarkers, as well as hematological parameters, suggesting potential adverse effects at high doses. Further research is recommended to establish safe dosages and explore long-term effects before recommending extended use of MSMLE for therapeutic purposes Keywords: Musa sapientum Lin, Toxicity evaluation, Phytochemical analysis, traditional medicine, and Wistar albino rats

Phytochemical profiling and anticancer potential of gardenia latifolia extracts against arsenic trioxide induced liver fibrosis in rat model.

Arsenic trioxide (As2O3) is an environmental contaminant that may cause hepatic injuries. As2O3-induced liver injuries are detected as an underlying cause of hepatocellular carcinoma (HCC) around the globe. The present study aimed to investigate the potential of Gardenia latifolia (GL) extracts against oxidative stress and apoptotic activity in HCC-induced rats and to explore in silico molecular docking analysis of phytocompounds of G. latifolia. The present study was designed to investigate the hepato-protective effect of ethanol and n-hexane extract of G. latifolia. Phytochemical analysis was performed using gas-chromatography-mass spectrometry (GC-MS), and the identified metabolites were used for computational docking analysis. The binding potential and inhibitory effect of the identified metabolites against inflammatory markers were assessed. Fifty male albino rats were selected for the in vivo study and were randomly divided into five groups, with 10 rats in each group. Group I is the control group. Hepatotoxicity was induced in groups II, III, IV, and V with 350mg/kg/day of As2O3. Group II was taken as positive control, Group III and IV were treated with ethanol and n-hexane extract of G. latifolia, respectively, and Group V was treated with cisplatin 3.0mg/kg/day. At the end of treatment, different stress and liver biomarkers were also analyzed. The quantitative phytochemical profiling revealed a high content of total flavonoid and tannins found at 5.731 ± 0.1856mg quercetin equivalent (QE)/g and 86.31 ± 14.20mg tannic acid equivalent (TAE)/g in G. latifolia n-hexane extract, while a significant concentration of TFC was 276.821 ± 2.19mg gallic acid equivalent (GAE)/g, in ethanolic extract. GC-MS analysis resulted in the identification of 26 metabolites in ethanol extract while 32 metabolites in n-hexane extract, respectively. Both the extracts restored the abnormal levels of stress markers (p < 0.05) in Groups III and IV, and were comparable to the comparative control group V, which was given cisplatin as the standard drug. The histopathological examination revealed the regeneration of hepatocytes, dilated sinusoidal cells, necrosis, and distorted hepatic architecture observed in arsenic trioxide hepatotoxic liver. Among the top most identified metabolites from GC-MS analysis, stigmasterol exhibited -8.3 and -7.1kcal/mol in silico binding affinities against cyclooxygenase-2 (COX-2), and interleukin (IL-6), respectively, while Dasycarpidan-1-methanol exhibited the best binding affinities of -6.8 and -7.2kcal/mole against matrixmetalloprotinease (MMP)-3 and heat shock protein-90 (HSP-90), respectively. 6-AH-cAMP showed the best docking score of -7.5kcal/mol for the vascular endothelial growth factor (VEGF) macromolecule. Metabolite Dasycarpidan-1-methanol, acetate represented drug like properties so it was further analyzed by MD simulation and stable dynamic nature of protein ligand complex was evaluated. In conclusion, the effective therapeutic potential of G. latifolia extracts targeted oxidative stress, increasing antioxidant activities and inhibiting inflammation and liver complications at early stages. Further research on the molecular level may further explore the anticancer potential of this plant against various types of cancers.

Current trends in electrochemical approaches for liver biomarker detection: a mini-review.

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin are well-established liver biomarkers with significant physiological functions. Alterations in these liver function tests can be indicative of the presence and progression of acute and chronic liver conditions such as liver cirrhosis, non-alcoholic fatty liver disease, biliary disease, and liver failure. Therefore, accurate and quantitative detection of these biomarkers is crucial for diagnosing and monitoring liver disease. There are several commercially available chemistry analyzers capable of simultaneously detecting all these biomarkers, as well as numerous biosensors designed for individual detection. Various techniques have been employed, including colorimetry, surface-enhanced Raman spectroscopy (SERS), electrochemiluminescence (ECL), fluorescence-based techniques, and electrochemical methods. Among these, electrochemical detection stands out due to its simplicity, cost-effectiveness, low sample volume requirement, label-free detection, high sensitivity, fast response times, miniaturization, and portability. Information on recently developed electrochemical biosensors is summarized through detailed tables and is intended to guide future research and development efforts in this area.

Assessment of Serum Prolactin Levels in Patients with Liver Disease: A Cross-sectional Study

Introduction: Prolactin is a hormone released from the anterior pituitary gland under tonic inhibitory control by dopamine. A decrease in dopamine levels is usually observed in decompensated liver disease, which could be due to its inhibition by the increased synthesis of false neurotransmitters. However, the level of serum prolactin in liver disease patients still remains disputed. Aim: To evaluate the serum prolactin levels in patients with liver disease of different aetiologies and compare them with healthy controls. Materials and Methods: The present cross-sectional study was conducted in the Department of Biochemistry from August 2021 to August 2022 at Amrita Institute of Medical Sciences (AIMS), Kochi, Kerala, India. A total of 100 patients with liver disease and 100 age- and gender-matched healthy controls were enrolled in the study. Serum prolactin was estimated using the Electro- Chemiluminescence Immuno Assay (ECLIA) technique. The serum prolactin levels were compared among patients with liver disease of different aetiologies and with healthy controls. Statistical analysis was carried out using the Mann-Whitney U test, Kruskal-Wallis test, and Dun Bonferroni test. Results: The median serum prolactin levels were significantly elevated in the cases {40.61 (29.13-70.24 ng/mL)} compared to the controls {17 (10.95-20.70 ng/mL)}, This p-value is correct as the median levels for cases is {40.61 (29.13-70.24 ng/mL)}. Comparison of prolactin levels showed no statistically significant difference based on the distribution of age and gender. In the present study, prolactin levels were found to be most prominent in patients with fatty liver disease. Conclusion: The serum prolactin level increased significantly in liver disease patients, particularly in patients with fatty liver. Hence, prolactin levels can be used as a useful predictive biomarker for fatty liver.

Protective potentials of polymyxin B and honey against bacterial lipopolysaccharide-induced endotoxemia in mice.

The experiment aimed to determine the effects of lipopolysaccharide (LPS), polymyxin B, and honey on survival rates, hematological parameters, liver and kidney biomarkers, blood glucose levels, serum insulin levels, and histopathology of the liver, kidney, lungs, brain, and pancreas in LPS-challenged mice. 50 male Swiss Albino mice (Mus musculus), aged 3 weeks, were randomly assigned into 5 groups (10 mice per group): Control group (A), LPS (2 mg/kg bwt/day IP in NS) treated group (B), polymyxin B (1.2 mg/kg bwt/day IM) pre-treated plus LPS (2 mg/kg bwt/day IP in NS) treated group (C), honey (10 gm/kg bwt/day PO) pre-treated plus LPS (2 mg/kg bwt/day IP in NS) treated group (D), both polymyxin B (1.2 mg/kg bwt/day IM) and honey (10 gm/kg bwt/day PO) pre-treated plus LPS (2 mg/kg bwt/day IP in NS) treated group (E). The LPS was administered intraperitoneally (IP) at 80 µg/mice/day, diluting in normal saline. After 16 weeks, the mice were sacrificed, and blood samples and organs (liver, kidney, lung, brain, and pancreas) were collected for laboratory tests. The results revealed that in LPS-treated mice, the mortality rate was the highest, and hemato-biochemical parameters were altered. Histopathological examination in the group treated with LPS showed disarrangement of hepatocytes, cellular infiltrations in the glomerulus, alveolar congestion in the lungs, several nerve fiber degenerations in the brain, and degenerative changes in pancreatic islets. The mortality rate and hemato-biochemical and histopathological changes were restored by the combined treatment of polymyxin B and honey. LPS has detrimental effects on survival rate and hemato-biochemistry, which are lessened by taking honey and polymyxin B supplements.

Protective Effect of Jamun (Syzygium cumini) Seed and Orange (Citrus sinensis) Peel Extracts Against Lead-Induced Alteration in Liver Biomarkers of Rats

Protective Effect of Jamun (Syzygium cumini) Seed and Orange (Citrus sinensis) Peel Extracts Against Lead-Induced Alteration in Liver Biomarkers of Rats

EFFECTS OF HIBISCUS SABDARIFFA L. TEA INTAKE ON ANTIOXIDANT RESPONSE AND BIOCHEMICAL PROFILE IN HEALTHY WISTAR RATS

Introduction: Hibiscus Sabdariffa L. have therapeutic potential characteristics, rich in phytochemicals with anti-inflamatory, antibacterial and antioxidant effects. Objective: The study aims to evaluate daily consumption of hibiscus tea, in a concentration usually consumed by population, on biochemical parameters and antioxidant activity in healthy female adult Wistar rats. Methodology: The animals were divide in Control Group (CG), which received filtered water and commercial diet; and Hibiscus Group (HG), which received 15 mL/day of Hibiscus Sabdariffa L. flower tea (prepared 1g of flower/100mL of water), commercial diet and filtered water. The infusion of hibiscus flower for tea preparation was performed daily (ratio of 1.0g of dried flower to 100 mL of filtered boiled water), infused for 10 minutes, strained, and daily offered to animals (15 mL/day/animal) during 84 days. After 84 days of experimental protocol, animals were euthanized and evaluated serum biochemical parameters such urea, creatinine, calcium, magnesium, phosphorus, iron, total proteins, albumin, lipid profile and fasting glycemia. Analysis of antioxidant components was perfomed on hibiscus tea and serum antioxidant activity data were also analyzed by 2,2-difenil-1-picrylhydrazyl (DPPH), Oxygen Radical Absorbance Capacity (ORAC) and total antioxidant activity by iron reduction (FRAP) methods. Results: Hibiscus tea has a high antioxidant potential, and reduce fasting glucose (p &lt; 0.05), but in concentration offered this antioxidant capacity was not observed at serum level, without changes on body mass, water intake, food consumption, lipid profile, liver and kidney biomarkers. Conclusion: Hibiscus tea daily consumption, showed higher antioxidant potential and reduce fasting blood glucose, without toxic effects.

Evaluation of fatty acids and carnitine as biomarkers of PFOS exposure in biota (fish and dolphin) from Galveston Bay and the northwestern Gulf of Mexico

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant that elicits a wide range of toxic effects in exposed biota. Coastal zones in highly urbanized or industrial areas are particularly vulnerable to PFOS pollution. At present, information is lacking on biomarkers to assess PFOS effects on aquatic wildlife. This study investigated the efficacy of l-carnitine (or carnitine) and fatty acids as biomarkers of PFOS exposure in aquatic biota. The levels of PFOS, total and free carnitine, and 24 fatty acids (measured as fatty acid methyl esters or FAMEs) were measured in the liver, and muscle or blubber, of fish and dolphins sampled from Galveston Bay and the northern Gulf of Mexico (nGoM). Overall, bottlenose dolphins (Tursiops truncatus) had the highest hepatic PFOS levels. Galveston Bay fish, gafftopsail catfish (Bagre marinus), red drum (Sciaenops ocellatus), and spotted seatrout (Cynoscion nebulosus), had hepatic PFOS levels ∼8-13× higher than nGoM pelagic fish species, red snapper (Lutjanus campechanus) and yellowfin tuna (Thunnus albacares). The multivariate analysis of PFOS liver body-burdens and biomarkers found carnitine to be a more modal biomarker of PFOS exposure than FAMEs. Significant positive correlation of hepatic PFOS levels with total carnitine was evident for biota from Galveston Bay (fish only), and a significant correlation between PFOS and total and free carnitine was evident for biota from the nGoM (fish and dolphins). Given the essential role of carnitine in mediating fatty acid β-oxidation, our results suggest carnitine to be a likely candidate biomarker of environmental PFOS exposure and indicative of potential dyslipidemia effects.

Rapid detection of heat stress biomarkers in Atlantic salmon (Salmo salar) liver using targeted proteomics

AbstractMost fish are ectothermic; therefore, their physiology is significantly affected by temperature. Aquaculture fish have limited ability to avoid elevated water temperatures, with impacts increasing as a result of climate change. To date, quantifying gene expression has been proposed to monitor heat stress in salmon liver. This study aimed to establish a faster multiplexed proteomics method to measure the abundance of thermal stress biomarkers in liver of salmon reared at 15°C or 20°C. Moreover, this study aimed to determine the effects that sample pooling, and data normalisation using housekeeping (HK) protein peptides would exert over the statistical significance of these thermal stress markers. A multiple reaction monitoring (MRM) mass spectrometry method, comprised 45 peptides derived from thermal stress markers and 10 peptides from HK proteins, was applied to measure these markers in liver of salmon reared at 15°C or 20°C. When samples were processed individually, 34 peptides were significant between salmon livers at 15°C or 20°C. In pooled samples, this decreased to five significant peptides. Peptides hprt1_HYADDLDR (hypoxanthine phosphoribosyl transferase) and gapdh_VPTPNVSVVDLTVR (glyceraldehyde‐3‐phosphate dehydrogenase) were the most stable and unstable HK protein peptides, respectively. When data was normalised with hprt1_HYADDLDR, 16 peptides were significant in individual samples and 13 in pooled samples. Significant peptides serpinh1a_ADLSNISGK, SerpinH1_TNSILFIGR, ela2_VVGGEDVR and gapdh_VPTPNVSVVDLTVR were common regardless of data strategy. A fast and reliable MRM method was established to validate thermal stress markers in salmon liver, where individual samples yielded better results than pooled samples. Sample pooling was only better when combined with normalisation as it validated twice the number of markers than sample pooling alone. This method could be applied to monitoring stress response in experiments involving feeding additives designed to mitigate thermal stress or in selective breeding programs to help understanding family variance in thermal tolerance.

Effects of Fish Oil Supplementation on Reducing the Effects of Paternal Obesity and Preventing Fatty Liver in Offspring.

Nonalcoholic fatty liver disease (NAFLD) is a serious public health concern, which calls for appropriate diet/nutrition intervention. Fish oil (FO) has several benefits in reducing obesity, but its intergenerational role in reducing the effects of paternal obesity has not been established. Hence, we hypothesized that FO supplementation to an obese father during the pre-conceptional period could improve the metabolic health of the offspring, specifically in the liver. Three groups of male mice were fed with a low-fat (LF), high-fat (HF), or high-fat diet supplemented with FO (HF-FO) for 10 weeks and were then allowed to mate with female mice fed a chow diet. Offspring were sacrificed at 16 weeks. The liver tissue was harvested for genomic and histological analyses. The offspring of HF and HF-FO fathers were heavier compared to that of the LF mice during 9-16 weeks. The glucose tolerance of the offspring of HF-FO fathers were significantly improved as compared to the offspring of HF fathers. Paternal FO supplementation significantly lowered inflammation and fatty acid synthesis biomarkers and increased fatty acid oxidation biomarkers in the offspring liver. In summary, FO supplementation in fathers shows the potential to reduce metabolic and cardiovascular diseases through genetic means in offspring.

Caesalpinia pulcherrima lowered serum carcinoembryonic antigen and antigen 125 in 7,12-Dimethylbenz[a]anthracene-induced Mammary Carcinogenesis in Female Albino Rats

AimThis study is aimed at evaluating the anticancer effect of the aqueous extract of Caesalpinia pulcherrima (L.) Sw in 7,12-Dimethlbenz[a]anthracene (DMBA) – induced mammary cancer. MethodsTumors were induced via a single intraperitoneal injection of DMBA (dissolved in olive oil) at a dose of 80 mg/kg body weight to the test rats and allowed to develop for about four months. They were treated with cyclophosphamide and an aqueous extract of Caesalpinia pulcherrima at doses of 10 and 250 mg/kg body weight, respectively, for 28 days. Serum levels of cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) activity, cyclooxygenase-2 (COX-2), and cytochrome p450 oxidase (cytp450) activity, as well as other diagnostic enzymes, were estimated. ResultsThe result revealed that DMBA is associated with a significant (p < 0.05) increase in the serum levels of CA125, CEA, COX-2, cytp450, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of the rats, thus suggesting tumor-promoting and hepatotoxic effects of DMBA. There was also a significant (p < 0.05) reduction of serum levels of these cancer and liver biomarker enzymes in the groups treated with cyclophosphamide and Caesalpinia pulcherrima compared to the untreated group, thus suggesting anticancer activity of Caesalpinia pulcherrima. The anticancer effect of Caesalpinia pulcherrima was further confirmed by the disappearance of infiltrative fibrous cells and the absence of inflammatory cells from the photomicrographs of the rats treated with Caesalpinia pulcherrima. ConclusionOur findings show that Caesalpinia pulcherrima possesses anticancer activity, and could protect against mammary cancer.

Effect of Fipronil Exposure on Hematological Aspects of Rhesus Monkeys (Macaca mulatta): Risk and Toxicity Assessment in Agro-Workers.

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. 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. 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. 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. 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.

Preventive and Therapeutic Effects of Epicatechin on Acetaminophen-Induced Liver Injury in Mice

Background: Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers. Objectives: In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy. Methods: The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated. Results: EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups. Conclusions: EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.

Exploring the Effects of Acute Stress Exposure on Lumpfish Plasma and Liver Biomarkers

This study aimed to expand knowledge on lumpfish stress physiology by investigating the effects of acute stress on primary (i.e., cortisol) and secondary (e.g., metabolites) stress responses, as well as oxidative stress biomarkers, from stress exposure to a recovery phase. The results showed that the lumpfish physiological response to 1 min air exposure is mild, in line with recent studies, and comparable to that described for white sturgeons. Cortisol seems to be the most reliable acute stress biomarker in lumpfish, with a significant increase in plasma 30 min after stress exposure, returning to resting levels 2 h after exposure. In contrast, glucose and lactate were not significantly altered by short-term air exposure. Effects on hepatic energy mobilisation were also detected following the acute stress. This study showed that acute 1 min air exposure seems tolerable, allowing a swift recovery. However, more studies on the impacts of air exposure and repeated acute stressors on lumpfish stress and immune responses are required to develop industry standards for lumpfish health and welfare monitoring.

Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA. We analyzed acetaminophen metabolites and liver biomarkers in plasma from SMA patients and healthy controls (HC) every hour for six or eight hours on day 1 and day 3 of treatment with therapeutic doses of acetaminophen. Twelve patients with SMA (six adults and six children) and 11 HC participated in the study. Adult patients with SMA had significantly lower clearance of acetaminophen compared to HC (14.1 L/h vs. 21.5 L/h). Formation clearance of acetaminophen metabolites, glucuronide, sulfate, and oxidative metabolites were two-fold lower in the patients compared to HC. The liver transaminases and microRNAs increased nine-fold in one adult SMA patient after two days of treatment. The other patients and HC did not develop abnormal liver biomarkers. In this study, patients with SMA had lower clearance and slower metabolism of acetaminophen, and one patient developed liver involvement. We recommend giving 15 mg/kg/dose to SMA adults (with a maximum of 4000 mg/day) and monitoring standard liver biomarkers 48 h after first-time treatment of acetaminophen.

Hepatoprotective Effects of Biochanin A on Thioacetamide-Induced Liver Cirrhosis in Experimental Rats.

The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect.