Markers Of Hepatic Function Research Articles

Comparison of Child-Turcotte-Pugh score and albumin bilirubin index score for advanced hepatocellular carcinoma at an LMIC tertiary cancer facility.

e16174 Background: Liver cancer, most commonly HCC, ranks third in cancer-related deaths. Hepatic dysfunction is a key factor in management. BCLC Staging uses CTP Score with objective biosynthetic and subjective parameters as ascites and encephalopathy. Albumin-bilirubin Index (ALBI) grade is an objective method of assessing hepatic dysfunction. Many studies have validated its predictive accuracy. The present study is an attempt to study the clinical profile, risk factor and to compare ALBI with CTP Score as a predictive marker of hepatic function in HCC. Methods: This is a prospective observational study from Feb 2022-Jan 2023. Patients with suspected HCC had physical examination and relevant lab investigations. Diagnosis is established with either appropriate imaging with raised AFP or by Histopathology. ECOG PS, CTP score, ALBI Grade, and BCLC Stage of HCC were assigned. Patients were treated accordingly and are being actively followed. The data was analysed using SPSS with appropriate statistical tests to study their clinical profile and the correlation between the two prognostic scores. Results: There were 54 new patients of HCC with 78.6% being males. Mean age of presentation was 60.88±10.6 yr, with majority had abdominal pain and distension. 78% were diagnosed on imaging with raised AFP. 31 had viral hepatitis with 19 having hepatitis B, and 12 Hepatitis C. 2 were HIV+ with Hepatitis B. 50% were alcoholic. 4 patients had active autoimmune conditions with 2 having RA, 1 had AIH and 1 having AS. 75% had cirrhosis with the majority having>50% liver involvement,61% having portal vein and bile duct invasion. 10,28, and 11 patients belonged to CTP class A,B and C respectively. 57% fell to BCLC Stage 3. 5,21,28 patients belonged to ALBI Grade 1,2 and 3 respectively. The higher ALBI Index had poorer biochemical, radiological profiles and BCLC Stages, signifying the similarity in prognostic severity. Positive correlation found between the CTP score and the ALBI grade (r=0.339; P Value=0.012). Conclusions: The above study concluded ALBI Index as a good prognostic tool for HCC management in low and middle-income countries. It has only 2 biochemical parameters, can easily be done on a single visit and as it correlates significantly with CTP Score.[Table: see text]

Effect of Oral Administration of Syzygium cumini Seed Powder on the Hepatic Function-related Enzymes of the Alcoholic Transport Laborers

Background: Syzygium cumini (locally known as Kalo Jam) seed powder is being used as folk medicine in various diseases since unknown times in Bangladesh. However, data on the systematic studies in human subjects are rare. Objective: To determine the effect of Syzygium cumini seed powder on the hepatic function-related enzymes of the alcoholic transport laborers. Methods: Here, we investigated the effects of oral administration of Syzygium cumini seed powder on hepaticfunction markers that included activities of Gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and renal-function markers such as creatinine and urea along with lipid profile, blood pressure and body mass index (BMI) upon chronic alcoholic human volunteers. Results: The levels of serum ALT, AST and GGT levels decreased, respectively, by 15.0, 8.5 and 23.0% after oral administration of the S. cumini powder in the alcoholic subjects. However, the levels of creatinine and urea were not altered significantly. In contrast, the effects of administration of S. cumini on the hepatic ALT, AST and GGT enzymes in the non-alcoholic control subjects were less prominent than those found in the alcoholic subjects. Blood pressure decreased only by 5-4 mmHg, while BMI was not altered in either the alcoholic or the non-alcoholic groups. Furthermore, there were significant reduction in the levels of TC (by 10%) and LDL-C (by >20%) and elevation of HDL-C (by 11%) in the S. cumini-prescribed alcoholic subjects. TC and LDL-C levels also decreased in the non-alcoholic subjects, but the rate was not statistically significant. Conclusions: Our results suggest that S. cumini seed extract ameliorated GGT, ALT and the atherosclerotic lipid parameters TC and LDL-C without having a significant side effect on the kidney functions, as indicated by the unaltered levels of serum creatinine levels in the alcoholic human subjects without any effect on BP and BMI of the same subjects. Thus, alcohol drinkers can be advised to intake S. cumini seed powder to protect against the oxidative hepatic damage. Bangladesh Medical Res Counc Bull 2022; 48: 97-104

Phytochemical profiling, antioxidant potential and protective effect of leaves extract of tunisian Vitis vinifera autochthonous accessions against acute CCl4-injured hepatotoxicity in mice

Vitis vinifera leaves (VVL) are agro-industrial waste. In the current study, the phytochemical profile of V. vinifera leaves extracts (VVLE) of two Tunisian autochthonous accessions was determined via LC-UV-ESI/MS, and their antioxidant and hepatoprotective properties were also assessed. Mice were pretreated orally with VVLE (7.5, 15 and 30 mg/kg) for 7 days, and then received acutely and by i.p. a solution CCl4 at 12% in sunflower oil (v/v). Serum levels of hepatic markers, oxidative stress indicators in liver tissue and histological changes were assessed. LC-UV-ESI/MS analysis revealed four phenolic compounds identified in both extracts with quercetin-3-O-glucuronide being the dominant constituent (23.32 ± 1.06 vs. 10.24 ± 0.12 mg/g DM, p < 0.05 for wild and cultivated accessions, respectively). The Antioxidant activity revealed a significant difference between the genotypes. Moreover, the VVLE of the wild "Nefza-I" ecotype was the most active based on antioxidant assays. Furthermore, the results showed that pre-treatment, especially with VVLE, of the wild ecotype "Nefza-I", attenuated CCl4-induced acute liver injury in a dose-dependent manner, as demonstrated by the decrease in the activities of hepatic serum function markers. This was also evidenced by a decrease in the levels of lipoperoxidation and histological damage in the liver, as well as a restoration of antioxidant enzyme activities (SOD and catalase) and an increase in the hepatic glutathione content. Our results demonstrate that VVLE possesses protective effects on CCl4-induced liver injury. Overall, the wild ecotype "Nefza-I" extract could serve as an effective protector against CCl4-induced hepatocellular oxidative stress.

Clinicopathological correlation of aspartate aminotransferase-to-platelet ratio (APRI) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) with survival in esophageal carcinoma patients: a retrospective cohort analysis of 951 patients.

The objectives of the current study were to associate novel markers, including aspartate aminotransferase-to-platelet ratio (APRI) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) with survival in esophageal malignancy. A retrospective study in a tertiary care hospital (single-center) included 951 patients having diagnosed esophageal carcinoma of any age group. The median (interquartile range) age of study participants were 50 (38-60) years, including 43% males and 57% female patients, while the median (interquartile range) levels of AAR and APRI were 0.97 (0.81-1.25) and 0.19 (0.13-0.29), respectively. AAR was found to be higher in dysphagia for solids only and dysphagia for both liquids and solids rather than liquids only (P=0.002), while other associations included well-differentiated tumor grade (P=0.011), finding of esophageal stricture on esophagogastroduodenoscopy (P=0.015), and characteristic of mass on computerized tomography scan being both circumferential and mural (P=0.005). APRI was found to be higher in adenocarcinoma (P=0.038), and finding of circumferential±ulcerated mass on esophagogastroduodenoscopy (P<0.001). On survival analysis, adenocarcinoma (P<0.001), luminal narrowing (P=0.002), AAR greater than 1.0 (P=0.006), and APRI greater than 0.2 (P=0.007) were found to be poor survival predictors. On Cox proportional hazards regression, APRI was found to be more associated with poor survival than AAR (Hazard ratio: 1.682, 1.208-2.340, P=0.002). This study correlated clinical and pathological features of esophageal malignancy with noninvasive markers of hepatic function.

Hypoglycemic and hypolipidemic effect of pentaamino acid fullerene C60 derivative in rats with metabolic disorder.

Pentaamino acid fullerene C60 derivative is a promising nanomaterial, which exhibited antihyperglycemic activity in high-fat diet and streptozotocin-induced diabetic rats. This study investigates the effect of pentaaminoacid C60 derivative (PFD) in rats with metabolic disorders. Rats were assigned to 3 groups (of 10 rats each) as follows: Group 1 (normal control), group 2 included the protamine-sulfate-treated rats (the untreated group of animals with the model metabolic disorder); group 3 (Protamine sulfate + PFD) included the protamine-sulfate-treated model rats that received an intraperitoneal injection of PFD. Metabolic disorder in rats was initiated by protamine sulfate (PS) administration. The PS + PFD group was injected intraperitoneally with PFD solution (3mg/kg). Protamine sulfate induces biochemical changes (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) in the blood and morphological lesions in rat liver and pancreas. The potassium salt of fullerenylpenta-N-dihydroxytyrosine in protamine sulfate-induced rats normalized blood glucose level and the serum lipid profile and improved hepatic function markers. Treatment with PFD restored pancreas islets and liver structure of protamine sulfate-induced rats compared to the untreated group. PFD is a promising compound for further study as a drug against metabolic disorders.

Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis

BackgroundLong-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function. MethodsThirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed. ResultsThe serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes. ConclusionsPlasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms.

Protective activity of acetylsalicylic acid on biochemical markers of hepatic and renal function in rats administered with potassium bromate

Protective activity of acetylsalicylic acid on biochemical markers of hepatic and renal function in rats administered with potassium bromate

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3.

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI. Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS. Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3. Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

English

Alcohol consumption is a common well-known source of brain damages. This work aimed to evaluate the neuroprotective effect of Conyza aegyptiaca against ethanol-induced neurodegeneration in a Wistar rat binge drinking model. Animals, pretreated orally once a day during 3 days with the hydroethanolic extract of C. aegyptiaca (HECA 250 and 500 mg/kg), received daily intraperitoneally 7 g/kg of ethanol for 3 more days, concomitantly with HECA. Behavioral studies, brains tissue oxidative stress markers (MDA, GSH) assays, blood cell count and biochemistry analysis were performed. In vitro antioxidant activity using DPPH and FRAP tests and phytochemical tests were also realized. The negative geotaxis test showed that HECA 500 rats took significantly less time (3.24 &plusmn; 0.49 s, P&lt;0.05 vs Ethanol control) compared to their congeners of Ethanol control group (6.80 &plusmn; 1.267 s, P&lt;0.01 vs Sham). HECA treatment lowered significantly MDA levels (P&lt;0.05 vs Ethanol control) and significantly increased GSH levels (P&lt;0.05 vs Ethanol control). HECA treatment also significantly reduced the platelet count (P&lt;0.001 vs Ethanol control). Ethanol 7 g/kg i.p raised hepatic function markers ALT and AST (respectively +27%, P&lt;0.01 and +58.29%, P&lt;0.01 vs Sham), effects significantly reversed by HECA treatments. DPPH scavenging activity with an IC50 of 368.769 &plusmn; 16.467 &micro;g/mL and ferric ion reducing power with an EC50 of 139.65 &plusmn; 7.14 &micro;g/mL should be related to the polyphenolic compounds found in HECA, tannins and flavonoids in particular. C. aegyptiaca could therefore potentially protect the brain against situations of neurodegeneration such as those observed in acute ethanol neurotoxicity. Key words: Conyza aegyptiaca, ethanol, brain, antioxidant, neuroprotection, neurodegeneration.

Shilajit potentiates the effect of chemotherapeutic drugs and mitigates metastasis induced liver and kidney damages in osteosarcoma rats

Osteosarcoma is a primary malignant cancer of the bone identified by the direct formation of osteoid tissue or immature bone by cancer cells. The liver and kidneys represent two major secondary organs to which osteosarcoma metastasizes. In this study, we assessed Shilajit, a phytomineral diffusion traditionally used in Ayurvedic medicine, for its possible protective effects against metastasis induced liver and kidney damages in an osteosarcoma rat model. Osteosarcoma rats displayed typical dysregulation of serum levels of hepatic and renal functional markers (p < 0.05) including aspartate aminotransferase (AST)* and alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins, albumin, bilirubin, creatinine, urea, and uric acid. Changes in functional markers were also positively correlated with marked histopathological alterations in liver and kidney tissues. Whereas Shilajit's treatment of osteosarcoma rates in combination with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy drug cocktail significantly (p < 0.05) reversed the studied functional markers to their near-normal levels. Co-treatment of shilajit and drug cocktails also markedly alleviated histopathological changes in liver and kidney tissues. Correlation co-efficient analysis of hepatic and renal functional markers revealed a significant inter-association among these markers. Collectively, present data indicate that shilajit may potentiate the effects of chemotherapy drugs and mitigate the metastasis-induced liver and kidney damage in osteosarcoma. Thus, the findings of this study substantiate the beneficial health effects of shilajit and promote its regular consumption.

Dipeptide IF and Exercise Training Attenuate Hypertension in SHR Rats by Inhibiting Fibrosis and Hypertrophy and Activating AMPKα1, SIRT1, and PGC1α.

Bioactive peptides are physiologically active peptides produced from proteins by gastrointestinal digestion, fermentation, or hydrolysis by proteolytic enzymes. Bioactive peptides are resorbed in their whole form and have a preventive effect against various disease conditions, including hypertension, dyslipidemia, inflammation, and oxidative stress. In recent years, there has been a growing body of evidence showing that physiologically active peptides may have a function in sports nutrition. The present study aimed to evaluate the synergistic effect of dipeptide (IF) from alcalase potato protein hydrolysates and exercise training in hypertensive (SHR) rats. Animals were divided into five groups. Bioactive peptide IF and swimming exercise training normalized the blood pressure and decreased the heart weight. Cardiac, hepatic, and renal functional markers also normalized in SHR rats. The combined administration of IF peptide and exercise offer better protection in SHR rats by downregulating proteins associated with myocardial fibrosis, hypertrophy, and inflammation. Remarkably, peptide treatment alongside exercise activates the PI3K/AKT cell survival pathway in the myocardial tissue of SHR animals. Further, the mitochondrial biogenesis pathway (AMPKα1, SIRT1, and PGC1α) was synergistically activated by the combinatorial treatment of IF and exercise. Exercise training along with IF administration could be a possible approach to alleviating hypertension.

The Effects of Use of Long-Term Second-Generation Antipsychotics on Liver and Kidney Function: A Prospective Study.

(1) Background: The second-generation antipsychotics (SGAPs) induce metabolic and inflammatory side effects, but documentation of their effects on the liver and kidneys is scarce. Aim: To study the three-year fluctuation of selected markers of renal and hepatic function in forensic psychiatric patients receiving SGAPs for more than five years. (2) Methods: Thirty-five forensic psychiatric patients (N = 35) were classified into two groups according to the type of SGAPs used for their treatment and the relevant risk of weight gain and metabolic complications. The three-year medication history, anthropometric data and biochemical data relevant to renal and hepatic function were retrieved from the individual medical files, specifically: serum levels of urea, uric acid, creatinine, alkaline phosphatase and amylase; the liver function enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma-glutamyl transpeptidase(γ-GT), and also the inflammatory index C-reactive protein (CRP). (3) Results: The patients receiving the SGAPs with a low risk for weight gain showed no significant fluctuation in the biochemical markers over the three-year period. The patients receiving the SGAPs with a high risk for weight gain showed significant differences between at least two measurements of uric acid (p = 0.015), SGOT (p = 0.018) and SGPT (p = 0.051). They showed significantly higher levels of creatinine in the third year compared to the second year (p = 0.029), and SGOT in the second year compared to the first (p = 0.038), and lower levels of SGPT in the third year compared to the second (p = 0.024). (4) Conclusion:In addition to consideration of possible metabolic and inflammatory complications, the choice of an antipsychotic drug for long-term treatment should also take into account the risk of hepatotoxicity and kidney damage.

Effect of Theobroma cacao L. on the Efficacy and Toxicity of Doxorubicin in Mice Bearing Ehrlich Ascites Carcinoma.

Background and objective: Doxorubicin is a widely used chemotherapeutic agent that causes oxidative stress leading to cardiotoxicity, hepatotoxicity, and nephrotoxicity. In contrast, Theobroma cacao L. has been recorded as an anticancer agent and found to be protective against multiple chemical-induced organ injuries, including heart, liver, and kidney injuries. The present study investigated the possible role of extracts from T. cacao beans for organ-protective effects in doxorubicin-induced toxicity in mice bearing Ehrlich ascites carcinoma (EAC). Methodology: After survival analysis in rodents, cocoa bean extract (COE) was investigated for its efficacy against EAC-induced carcinoma and its organ-protective effect against doxorubicin-treated mice with EAC-induced carcinoma. Results: Significant reductions in EAC and doxorubicin-induced alterations were observed in mice administered the COE, either alone or in combination with doxorubicin. Furthermore, COE treatment significantly increased the mouse survival time, life span percentage, and antioxidant defense system. It also significantly improved cardiac, hepatic, and renal function biomarkers and markers for oxidative stress, and it also reduced doxorubicin-induced histopathological changes. Conclusion: COE acted against doxorubicin-induced organ toxicity; potent antioxidant and anticancer activities were also reflected by the COE itself. The COE may therefore serve as an adjuvant nutraceutical in cancer chemotherapy.

Spirulina and C-phycocyanin mitigate titanium dioxide nanoparticle-induced hematobiochemical and hepatorenal disorders through antioxidative pathway

The present investigation is designed to evaluate the ameliorative efficacy of spirulina and its active constituent, C-phycocyanin, on hepatorenal injury induced by titanium dioxide nanoparticles (TiO2 NPs). Forty-eight male albino rats were randomly divided into six groups: control group, Spirulina treated group, C-phycocyanin treated group, TiO2 NPs treated group, TiO2 NPs+ Spirulina treated group and TiO2 NPs+ C-phycocyanin treated group. The estimation of hepatic and renal function markers and oxidative status as well as histopathologic alterations in hepatic and renal tissues were analyzed. Spirulina and C- phycocyanin treatments caused significant improvement in all hematological indices such as RBCs, Hb, HCT, and total and differential WBCs relative to the untreated TiO2 NPs group. Also, spirulina and C-phycocyanin treatments significantly alleviated hepatic enzymes and bilirubin concentrations. Oral administration of spirulina and C- phycocyanin decreased total cholesterol and triglycerides content significantly. Both Spirulina and C- phycocyanin attenuated creatinine, urea, and uric acid significantly. Furthermore, the present study revealed that spirulina and C- phycocyanin significantly increased hepatorenal antioxidants content and retard malondialdehyde (MDA) formation. Histopathological examinations displayed that both spirulina and C- phycocyanin treatments repaired mostly the abnormal architecture of hepatic and renal tissues induced by TiO2 NPs. In conclusion, the modulatory role of spirulina and C-phycocyanin may be due to their strong antioxidative effects and other active constituents of spirulina.

Effect of soaked and fermented raspberry wines on the liver in mice

Evidence has shown that some dietary polyphenols (flavonoids, phenolic acids, tannins, lignans, saponins, terpenoids, etc.) can alleviate alcoholic liver disease (ALD). Raspberries, the fourth most significant fruit worldwide, comprise a particular phytochemical profile encompassing ellagitannins and anthocyanins and exert many biological activities. In contrast to Chinese liquor (named Baijiu in China), the effect of two kinds of raspberry wines (fermentation and soaking types) on the liver is poorly understood. This study aimed to evaluate the effect of the two types of raspberry wines on the liver in a mouse model. The results showed that the livers of mice treated with raspberry wines produced less malondialdehyde, hepatic function markers, and proinflammatory cytokines, and less lipid accumulation in the serum and liver was also found compared to the mice treated with Baijiu. The activities of antioxidant markers in the liver from the raspberry wine supplementation group were higher than those receiving Baijiu. This study demonstrated that raspberry wines provoked more minor liver injury than Baijiu. The degree of liver damage caused by soaked raspberry wine was lower than that induced by fermented raspberry wine.

Association of changes in NT-proBNP, hsTnT and uric acid levels with haemodynamic changes after targeted medical therapies in patients with idiopathic pulmonary arterial hypertension.

During pulmonary arterial hypertension (PAH)-targeted therapies for patients with idiopathic pulmonary arterial hypertension (IPAH), regular follow up to evaluate treatment efficacy is essential. Serum biomarkers can reflect various pathobiological processes in IPAH and have the advantages of being non-invasive, simple to carry out and low cost. The aim of our study was to evaluate whether serum biomarkers could serve as non-invasive markers to reflect haemodynamic changes after PAH-targeted therapies in patients with IPAH. A total of 31 eligible patients aged 38.1 ± 12.1 years (25 were female) were included in this study. Changes in haemodynamic parameters and several serum biomarkers (cardiac markers, serum uric acid, high-sensitivity C-reactive protein, hepatic and kidney function markers) were compared before and after at least six months of PAH-targeted therapies. The time interval between the blood assays and right heart catheterisation was within five days. After at least six months of PAH-targeted therapies, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level decreased from 579 (191-905) to 135 pg/ml (60-395) (p < 0.01), high-sensitivity cardiac troponin T (hsTnT) level decreased from 0.009 (0.006-0.012) to 0.007 ng/ml (0.005-0.01) (p < 0.01), and serum uric acid level decreased from 381.5 ± 131.4 to 327.2 ± 110.0 µmol7sol;l (p = 0.011). The change in NT-proBNP level was positively correlated with changes in pulmonary vascular resistance (r = 0.538, p < 0.01) and mean pulmonary arterial pressure (r = 0.440, p = 0.013). The change in hsTnT level was positively correlated with the change in mean right atrium pressure (r = 0.504, p < 0.01). The change in serum uric acid level was negatively correlated with that of cardiac index (r = -0.471, p < 0.01). NT-proBNP, hsTnT and serum uric acid levels can be used as non-invasive tools for evaluating the efficacy of PAH-targeted medications for IPAH patients. The role of these biomarkers in the follow up should be emphasised.

The ameliorative efficacy of Thymus vulgaris essential oil against Escherichia coli O157:H7-induced hematological alterations, hepatorenal dysfunction and immune-inflammatory disturbances in experimentally infected rats.

The purpose of the present study was to evaluate the possible ameliorative role of Thymus vulgaris (T. vulgaris) essential oil against Escherichia coli O157:H7 (E. coli O157:H7) deleterious effects in both blood and different tissues of rats by assessing the hematological, biochemical and immune-inflammatory parameters besides the histopathological alterations in the different organs. Forty male rats were randomly divided into four equal groups as follows: group I served as control, group II orally inoculated with E. coli O157:H7 at a dose of 1.0 × 109cfu/ml, group III orally received 250mg/kg BW T. vulgaris oil daily for 7days and group IV orally inoculated with E. coli O157:H7 as the same dose of group II and orally received T. vulgaris oil as the same dose and duration of group III. Bacterial challenge in groups II and IV was once at the beginning of experiment and administration of oil began after 72h from bacterial inoculation. At the end of the study, blood was sampled and complete blood picture, liver and kidney function alongside immunoglobulins and cytokines concentrations were estimated and tissues of large intestine (colon), liver and kidneys were collected for histopathological examinations. The results revealed that there was an increase of red blood cells count, hematocrit value and hemoglobin concentration besides white blood cells and thrombocytes counts and substantial increment of serum markers of hepatorenal damage such as the activities of transaminases and concentrations of bilirubin (total, direct and indirect), total proteins, albumin, creatinine and urea in E. coli O157:H7-challenged group. Also, there was a considerable increase in serum immunoglobulins M and G, interleukin 6 and 8 and tumor necrosis factor alpha as well as decreased serum alkaline phosphatase activity. Moreover, T. vulgaris oil could partially improve the hematological, biochemical and histopathological alterations induced by E. coli O157:H7 without any significant alterations in all measured parameters when used alone. The study concluded that the T. vulgaris oil relatively diminished the alterations in hematological parameters, hepatic and renal function markers and immune-inflammatory variables alongside the histopathological changes in different organs induced by E. coli O157:H7. The ameliorative effects of T. vulgaris oil are mediated through its anti-inflammatory, antioxidant and immunomodulatory activities.

Gibberellic acid-induced hepatorenal dysfunction and oxidative stress: Mitigation by quercetin through modulation of antioxidant, anti-inflammatory, and antiapoptotic activities.

The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3 on liver and kidney function and the effect of quercetin on the hepatorenal toxicity induced by GA3 in four groups of male albino rats. For 4weeks, the control group (CNT) received saline, the quercetin group (QR) received daily intraperitoneal injections of quercetin (50mg/kg/BW) dissolved in saline, the gibberellic acid group (GA3) received GA3 (55mg/kg/BW) via oral gavage, and the protective group (QR) was injected with quercetin and gavaged with GA3 in the same doses used in the QR and GA3 groups (50mg/kg/BW +GA3 and 55mg/kg/BW). GA3 induced liver and kidney injury, as shown by elevated serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase,and gamma-glutamyl transferase (GPT, GOT, and GGT) as well as increased levels of creatinine, urea, and uric acid. Hepatorenal toxicity was demonstrated by a significant increase in levels of serum and tissue malondialdehyde (MDA) and decreased antioxidant enzyme activity, such as catalase (CAT) and superoxide dismutase (SOD), accompanied by a subsequent decrease in glutathione peroxidase (GPx) levels in liver and kidney tissue of GA3-treated rats. Administration of quercetin (QR) significantly protected hepatorenal tissue against the toxic effect of GA3 through normalization of the hepatic and renal function markers. It also retrieved the antioxidant ability by modulating the hepatorenal toxic effect at the molecular level through upregulation of antiapoptotic genes and downregulation of transforming growth factor-β1 (TFG-β1), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Impairment of liver and kidney function was confirmed by histologic and immunohistochemical analyses. Pretreatment with quercetin was effective at attenuating histopathologic changes in hepatic and renal tissues by regulating the immunoexpression of caspase-3 and Bcl-2 to return them to more normal values. PRACTICAL APPLICATIONS: The confirmed hepatorenal dysfunction caused by GA3 was ameliorated by quercetin administration. Moreover, quercetin demonstrated the potential to reverse hepatorenal dysfunction by regulating inflammatory and antioxidant properties, inhibiting the production of free radicals and inflammation-associated cytokines, and modulating antioxidants and antiapoptotic activity.

Leaf extract of Coffea arabica L. reduces lipid peroxidation and has anti-platelet effect in a rat dyslipidemia model

This study aimed to evaluate the antioxidant potential of the Coffea arabica Lineu (L.) leaf extract and its effects on platelet aggregation of dyslipidemic rats. The extract was obtained by the percolation of C. arabica L. leaves in hydroethanolic solution 70% (v/v). The mass spectrometry FIA-ESI-MS² suggested the presence of chlorogenic acid, rutin acid, and quinic acid. The DPPH• radicals scavenging capacity was demonstrated (IC50 = 0.06 mg/mL). The extract was administered to rats by gavage (300 mg/kg/day) for 56 days. Dyslipidemia was induced by administering Triton WR-1339 (300 mg/kg body weight) on the 54th day. On day 56, blood was collected by puncturing the abdominal aorta artery and the aortic artery was removed. Lipid profile, markers of renal and hepatic injury, lipid peroxidation, and platelet aggregation tests were carried out. The ingestion of extract reduced the lipid peroxidation (aorta and plasma) and platelet aggregation in dyslipidemic rats. The extract did not affect markers of renal and hepatic function as analyzed in this study, suggesting neither impaired liver nor kidney function in these animals. Therefore, our results demonstrate that the extract of leaves of C. arabica L. show antioxidant potential in vitro and in vivo as well as anti-platelet aggregation in dyslipidemic animals.

Cow–calf efficiency of beef cows grazing different herbage allowances of rangelands: hepatic mechanisms related to energy efficiency

Context Improvement in efficiency of energy utilisation of cow–calf systems could benefit beef production profitability and sustainability. Energy efficiency has been associated with mitochondrial function; therefore, hepatic mitochondrial function and oxidative stress could play a key role in energy efficiency of beef cows. Aim We evaluated the effect of two herbage allowances from rangelands (Campos biome) on cow–calf energy efficiency, hepatic mitochondrial density and function, and oxidative stress of purebred (Hereford and Aberdeen Angus) and reciprocal F1 crossbred beef cows. Methods Mature cows (n = 32) were used in a complete randomised block design with a factorial arrangement of herbage allowance (2.5 vs 4 kg dry matter/day; low vs high) and cow genotype (pure vs crossbred) over 3 years. At the end of the third year, cows were slaughtered at 190 ± 10 days postpartum. Liver was dissected and weighed, and samples were collected and snap-frozen pending analysis of mitochondrial density and oxidative stress markers. Estimated cow–calf energy efficiency was calculated by using total cow estimated metabolisable energy intake as input and calf energy retained at weaning as output. Key results Cow–calf energy efficiency was greater (P ≤ 0.07) for high than low herbage allowance and for crossbred than purebred cows. Mitochondrial density biomarkers (hepatic citrate synthase enzyme activity, citrate synthase mRNA, and mitochondrial:nuclear DNA ratio) were greater (P ≤ 0.03) for high than low herbage allowance. Plasma pro-oxidants and plasma antioxidant capacity were greater (P ≤ 0.07) for crossbred than purebred cows. Plasma oxidative stress index and expression of hepatic 4-hydroxynonenal protein adducts were affected (P ≤ 0.06) by herbage allowance × cow genotype interaction. Conclusion Greater cow–calf energy efficiency was associated with greater hepatic mitochondrial density without differences in mitochondrial function. Contrary to expectation, greater efficiency of crossbred than purebred cows was associated with increased hepatic oxidative damage, which probably reflects greater liver metabolic activity in crossbreds. Implications Herbage allowance and cow genotype affect cow–calf efficiency, hepatic mitochondrial function and oxidative stress markers. Greater efficiency of crossbred cows seems associated with increased hepatic oxidative damage.