Plasma Total Bilirubin Research Articles

Metabolic and performance responses to the replacement of lactose by fat in milk replacer formulations for dairy calves

The recent trend in the dairy industry towards elevated planes of milk feeding of young calves requires reconsideration of calf milk replacer (CMR) formulations. The fat:lactose ratio in CMR is typically lower than that of whole milk and effects of increasing fat inclusion at the expense of lactose in CMR on nutrient metabolism and gut function of rearing calves are not sufficiently understood. Therefore, the current study aimed to determine the effect of increasing replacement of lactose by fat on growth performance, nutrient digestibility and metabolism, and glucose/insulin sensitivity. A total of 40 male calves (1.7 ± 0.10 days of age, 46.7 ± 0.76 kg BW) were blocked based on arrival date and randomly assigned to one of four treatments containing differing levels of fat and lactose (18F: 18.8% and 47.6%; 22F: 22.3% and 42.8%; 26F: 26.0% and 38.6%; 30F: 30.1% and 33.8%, fat and lactose DM, respectively). Calves were individually housed for the duration of the 11 week study and received their CMR (150 g/L) twice a day (0700 and 1600 h) from a teat bucket. The CMR feeding schedule consisted of 6 L/d from d 2 to 14, 7 L/d from d 15 to 56, and then 4 L/d during gradual weaning from 56 to 63 days. Pelleted starter, chopped straw, and water were available ad libitum throughout the study. Measurements included feed intake, growth, nutrient digestibility, fecal composition, and blood parameters. A glucose tolerance test (GTT) was performed between 28 and 32 days of age. By design, metabolizable energy intake from CMR increased linearly with fat level, but this did not result in a difference in BW, ADG, or concentrate intake. Fecal composition remained unaffected by treatment except for higher fat content in 22F compared to 26F. Also, plasma non-esterified fatty acids and total bilirubin differences were limited to 22F having the highest values whereas 26F had the lowest values. Regarding the GTT, total area under the curve (AUC) for glucose was highest in 22F and 26F and lowest in 18F whereas the AUC between 30 and 60 min for glucose was highest in 26F and lowest in 18F and 22F. Overall, altering the lactose:fat ratio in CMR did not affect growth performance while having minor effects on nutrient metabolism, but future investigation should focus on physiological consequences and effects in adult life to understand biological impact of fat and lactose levels in CMR for rearing calves.

Neonatal hyperbilirubinemia management: Clinical assessment of bilirubin production

The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China.

Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: A meta-analysis of randomized clinical trials.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function. Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis. SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p < 0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p < 0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p < 0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p < 0.0.1). Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.

Oral Acute &amp; Sub-Chronic Toxicity Assessment of Ethanol Leaf Extract of Simarouba glauca

Traditional herbal medicine and their preparations have been widely used for thousands of years and are still in use in developing and developed countries owing to their medicinal values and their presumed relative safety. This belief that medicinal plants are not toxic or are with less side effect due to their natural origin is debatable; hence this study was conducted to evaluate the safety and (or) toxicity of Ethanol leaf extract of Simarouba glauca (EESG) on liver, kidney and heart functions of Wistar rats. The oral acute toxicity of EESG was evaluated in line with Lorke’s method. The sub-chronic toxicity of EESG was carried out according to the OECD guidelines with modification and using a total of twenty-four (24) male Wistar rats; divided into four groups of six rats each, following a two-week acclimatization. Test rats were orally administered EESG at doses of 500, 1000 and 2000 mg/kg body weight respectively daily for thirty (30) days, while the control was given only feed and water ad libitum. At the end of the experiment, the rats were fasted overnight and sacrificed under chloroform anesthesia; relevant biochemical and histopathology analyses were carried out. The data obtained from the oral acute test indicate that the LD50 was above 5000 mg/kg and there was no death recorded. There were significant increases (P ˂ 0.05) in percentage (%) body weight of rats administered respective doses of EESG. There were significant reductions (P˂0.05) in mean liver: body weight ratio of rats administered EESG 500 and 2000 mg/kg respectively, significant reductions (P˂0.05) in mean kidney: body weight ratios of rats given EESG 1000 and 2000 mg/kg respectively; significant reductions (P˂0.05) in mean heart: body weight ratios of test rats administered EESG 2000 mg/kg; whereas others were not significantly different (P˃0.05) relative to their respective control. Plasma ALT and GGT activities of rats administered respective dose of EESG were significantly reduced (P˂0.05); plasma ALP activities were significantly elevated (P˂0.05) relative to the control after 30 days. There were no significant differences (P˃0.05) in plasma total proteins and albumin levels. Plasma total and unconjugated bilirubin of rats administered respective dose of EESG were not significantly different (P˃0.05); whereas, rats given EESG recorded significant reduction in plasma conjugated bilirubin. Plasma urea was significantly elevated (P˂0.05) in rats administered EESG 1000 and 2000 mg/kg respectively. Test rats given EESG 500 and 1000 mg/kg respectively recorded significant elevations in plasma creatinine and rats given EESG 2000 mg/kg recorded significant decrease in plasma creatinine levels; others were not significantly different relative to the control. Plasma chloride and potassium ion levels of rats administered respective doses of EESG were not significantly different (P˃0.05); significant reduction (P˂0.05) in plasma sodium ions concentration in all group compared to the control. Plasma calcium ion levels in all group were not significantly different (P˃0.05); whereas there were significant reductions (P˂0.05) in plasma bicarbonate ion levels relative to their respective controls. Although plasma ALP activity were significantly elevated, there were no elevations in specific liver function enzymes and no visible hepatocellular damage. Furthermore, the conspicuous elevations observed in plasma urea and creatinine levels do not exclusively indicate EESG-induced organ injury. Therefore, it is suggestive that EESG was not significantly toxic to the to the liver, kidney and heart respectively and may be administered at lower doses in further studies.

Intestinal Epithelial Cell-specific Deletion Of Hif1a Affects The Intestinal Barrier Function In High-fat Diet-fed Mice

High-fat diet (HFD) feeding disrupts the intestinal barrier integrity, inducing the translocation of bacteria into the portal circulation, leading to the whole-body inflammation. Intestinal epithelial cells (IEC), producing antimicrobial proteins to prevent the attachment and entry of pathogens, are affected by the tissue hypoxia. The hypoxia-inducible factor (HIF)-1α is pivotal in the transcriptional response to oxygen flux. PURPOSE: To determine the role of HIF-1α signaling pathway in the regulation of intestinal barrier function on HFD fed mice. METHODS: The Villin-Cre mediated, IEC-specific deletion of Hif1a (Hif1aVKO) and the control Hif1afl/fl mice (male, 8-week) were used in this study. The Hif1aVKO and Hif1afl/fl were fed HFD (HFD-Hif1aVKO and HFD-Hif1afl/fl, n=6/group) or normal chow for 12 weeks. Immediately after euthanasia, the serum, abdominal fat, intestine and feces were sampled. The intestinal mucus structure was observed by the AB-PAS staining. The intestinal permeability was quantified with FITC-dextran. Fasting plasma glucose, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol levels were measured. The fecal microbial DNA was extracted and sequenced on an Illumina MiSeq platform. Student's t-tests and one-way ANOVA were used. Differences with P<0.05 were considered significant. All animal experiments were performed in compliance with and approved by the Shanghai University of Sport ethical review board. RESULTS: We found that HFD feeding markedly increase the intestinal permeability without significant morphological changes. Compare with HFD-Hif1afl/fl, the HFD-Hif1aVKO mice were higher in the body weight (40.55±3.94 vs. 35.06±5.31 g, p<0.05), TG (1.75±0.56 vs. 1.08±0.31 mmol/l, p<0.05), TC(4.28±0.92 vs. 3.74±0.56, p<0.05) and LDL-C(0.83±0.08 vs. 0.68±0.14, p<0.05). Principal coordinates analysis based on unweighted Unifrac distances highlighted a clear clustering of the microbial populations of Hif1aVKO away from that of Hif1afl/fl. CONCLUSIONS:IEC HIF-1α signaling is involved in the intestinal barrier function maintenance in HFD fed mice. Supported by the National Natural Science Foundation of China (31701040, 31801003 and 31471135).

The Observation of Liver and Kidney Injury and the Activation of Macrophages in the Overload Pressure Induced Cardiac Hypertrophy/Heart Failure Mouse Model

The purpose of this study is to investigate the injury of liver and kidney tissues in overload pressure induced cardiac hypertrophy/heart failure mice model and the changes of macrophage activation level. 6-8 week-old C57BL/6 mice were subjected to transverse aortic constriction (TAC) surgery to establish the cardiac hypertrophy/heart failure mouse model induced by pressure overload, while the aortic was not ligated in the Sham group. At 4 weeks and 8 weeks after TAC, the mice of each group were subjected to echocardiography and blood collection. And mice were sacrificed to collect samples of the heart, liver, and kidney tissues. The contents of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and serum creatinine (Scr) in Sham group and two operation groups were determined. The histological changes of liver, heart and kidney tissues were observed by HE staining, and the expression of the marker of macrophage activation, F4/80 protein, was detected in the heart, liver and kidney tissue by immunohistochemical staining. Cardiac hypertrophy occurred at 4 weeks after TAC operation in C57BL/6 mice and developed into heart failure at 8 weeks after TAC. The echocardiography showed that, compared with the Sham group, the left ventricular end-diastolic posterior wall thickness (LVPWd) and the left ventricular internal diameter in diastole (LVIDd) were significantly increased, while the left ventricular ejection fraction (EF) and the left ventricular fractional shortening (FS) were significantly decreased ( P<0.05) in the 4-week-TAC group and 8-week-TAC group. The plasma content of ALT, AST, TBil and Scr in the 4-week-TAC group and 8-week-TAC group were significantly higher than those in the Sham group ( P<0.05). HE staining showed obvious liver pathological changes in TAC mice, such as vacuolation, mild hepatic sinusoid congestion and inflammatory infiltration in mice post 4 weeks after surgery, and such liver injury was worse in mice post 8 weeks after surgery. Besides, there was a slight damage in renal tissue shown by HE staining, such as slight glomerular injury and slight bleeding. F4/80 protein immunohistochemical staining results demonstrated that the activation of macrophages in the heart and liver in the 4-week-TAC group and 8-week-TAC group was significantly increased than that in the sham group ( P<0.05), but there was no significant difference in kidney tissues in groups. Macrophages are involved in the process of liver and kidney injury in cardiac hypertrophy/heart failure.

PEG‐asparaginase‐induced hepatic steatosis is associated with PKA activation and white adipose tissue lipolysis

BackgroundPEGylated L‐asparaginase (PEG‐ASNase) is an essential chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL) that depletes L‐asparagine and leads to leukemic cell apoptosis. However, this agent is avoided in adult ALL protocols due to its high risk of liver toxicity. Clinical studies have implied that the mechanism of PEG‐ASNase‐induced liver toxicity is due to defect in hepatic β oxidation; however, no study has investigated the mechanism or the role of β oxidation in PEG‐ASNase‐induced hepatic toxicity. Our study aims to demonstrate that PEG‐ASNase‐induced liver toxicity is not due to hepatic defects in fatty acid oxidation, VLDL secretion, or fatty acid synthesis. Rather, our data suggest that the toxicity may be due to a novel mechanism of fatty liver involving drug‐induced adipose lipolysis.Methods8‐week‐old male Balb/c mice received 1,500 IU/kg of PEG‐ASNase and were sacrifice at 1, 3, 5, or 7 days after drug administration. Blood, liver, and white adipose tissue (WAT) were harvested after sacrifice. Liver lipids were directly quantified and further assessed via Oil red O and H&amp;E staining. Total and direct bilirubin, ALT, AST, and non‐esterified fatty acids (NEFA) were measure in plasma. The mRNA and protein levels of genes involved in hepatic fatty acid oxidation, lipid synthesis, and VLDL secretion were determined. To assess the effect of PEG‐ASNase on WAT lipolysis, the protein levels of Atgl, phosphorylated Hsl, and protein kinase A (PKA) were measured.ResultsPEG‐ASNase treatment in mice led to total body, liver, and WAT weight loss. Mice developed hepatic microvesicular steatosis after 3–7 days of drug administration. Plasma direct and total bilirubin levels were elevated 8‐fold relative to controls, whereas ALT, AST, and NEFA concentrations were elevated 2‐fold 3–7 days after PEG‐ASNase. Furthermore, we found, that the hepatic mRNA and protein levels of Srebp‐1c and Fas, which are involved in fatty acid synthesis, were downregulated suggesting a decrease in lipid synthesis after PEG‐ASNase. Furthermore, the hepatic gene and protein expression of Pparα, Lcad, and Mcad, which are involved in fatty acid oxidation, were upregulated after PEG‐ASNase. In vivo VLDL secretion was also increased 3 days after PEG‐ASNase administration. Taken together, our data indicate that other lipid sources are mediating the drug‐induced fatty liver. Among WAT, we found that PEG‐ASNase elevated ATGL, phosphorylated HSL, and PKA protein levels, consistent with the WAT weight loss and the increased plasma NEFA levels.ConclusionOur data suggest that PEG‐ASNase‐induced WAT lipolysis leads to the development of microvesicular hepatic steatosis and toxicity. Our future studies will determine whether PEG‐ASNase hepatic steatosis can be inhibited via the pharmacological or genetic inhibition of adipose lipolysis and identify the molecular mechanism leading to PKA activation and lipolysis.Support or Funding InformationNIH Grants RO1 CA216815. University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261.

Hepatoprotective and hematological effects of Justicia secunda Vahl leaves on carbon tetrachloride induced toxicity in rats

ABSTRACTJusticia secunda Vahl is an exotic plant that is used to treat medical problems. We investigated the hepatoprotective and hematological effects of aqueous extracts of J. secunda leaves on carbon tetrachloride induced toxicity in rats. Leaf extracts were prepared using hot and cold extraction methods to obtain a hot extract of J. secunda leaves (JSHAE) and a cold extract of J. secunda leaves (JSCAE). Total phenol and flavonoid measurements and antioxidant assays were performed to determine the extract with the greater antioxidant activity. JSHAE was the more effective extract for treatment of carbon tetrachloride (CCl4) induced hepatotoxicity and hepatotoxicity in rats. Silymarin was used as a standard for comparison. We found that JSHAE contained more total phenol and flavonoid than JSCAE. JSHAE exhibited significantly greater ferric reducing antioxidant power and 1,1-diphenyl-2-picryl hydrazyl and thiobarbituric acid scavenging activity than JSCAE. We also found that in vivo, 100 and 200 mg/kg JSHAE significantly reduced plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total bilirubin levels following CCl4 induced toxicity compared to untreated rats. JSHAE treated animals exhibited white blood cell, red blood cell, hemoglobin, hematocrit, platelet and procalcitonin levels that were comparable to control animals. Liver sections of rats treated with 200 mg/kg. JSHAE exhibited no abnormalities.

Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis

BackgroundIn parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial. ObjectiveThe objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals. MethodsTotal PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans. ResultsIn a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05–2.08, P = 0.02). ConclusionOur data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

Histopathological features of chronic hepatitis B reactivation

It was aimed to investigate histopathological changes in acute hepatic exacerbations. A total of 20 patients, who developed acute hepatic exacerbation on the base of chronic hepatitis B infection, were enrolled in the study and liver biopsy was performed. Histological activity index (HAI) and its components, fibrosis scores and total HAI score were calculated according to the Ishak scoring system. All of the patients enrolled in the study had portal inflammation and spotty necrosis. Fibrosis was present in 17 patients. The median grade, stage and total HAI scores of the patients were 7 (2-14), 2 (0-3) and 8.5 (4-16), respectively. Positive correlation was determined between necroinflammation and ALT. While grade and total HAI score did not show significant difference among genders, fibrosis was significantly higher in males (p=0.008). The findings of this study showed that there are significant correlation between histopathologic changes (grade and total HAI score) in liver biopsy and plasma ALT, AST and Total bilirubin levels during acute hepatic exacerbation in patients with chronic hepatitis B infection.

Circulating total bilirubin and risk of non-alcoholic fatty liver disease in the PREVEND study: observational findings and a Mendelian randomization study

The relationship between circulating total bilirubin and incident non-alcoholic fatty liver disease (NAFLD) is uncertain. We aimed to assess the association of total bilirubin with the risk of new-onset NAFLD and investigate any causal relevance to the association using a Mendelian randomization (MR) study. Plasma total bilirubin levels were measured at baseline in the PREVEND prospective study of 3824 participants (aged 28–75 years) without pre-existing cardiovascular disease or NAFLD. Incident NAFLD was estimated using the biomarker-based algorithms, fatty liver index (FLI) and hepatic steatosis index (HSI). Odds ratios (ORs) (95% confidence intervals) for NAFLD were assessed. The genetic variant rs6742078 located in the UDP-glucuronosyltransferase (UGT1A1) locus was used as an instrumental variable. Participants were followed up for a mean duration of 4.2 years. The multivariable adjusted OR (95% CIs) for NAFLD as estimated by FLI (434 cases) was 0.82 (0.73–0.92; p = 0.001) per 1 standard deviation (SD) change in loge total bilirubin. The corresponding adjusted OR (95% CIs) for NAFLD as estimated by HSI (452 cases) was 0.87 (0.78–0.97; p = 0.012). The rs6742078 variant explained 20% of bilirubin variation. The ORs (95% CIs) for a 1 SD genetically elevated total bilirubin level was 0.98 (0.69–1.38; p = 0.900) for FLI and 1.14 (0.81–1.59; p = 0.451) for HSI. Elevated levels of total bilirubin were not causally associated with decreased risk of NAFLD based on MR analysis. The observational association may be driven by biases such as unmeasured confounding and/or reverse causation. However, due to low statistical power, larger-scale investigations are necessary to draw definitive conclusions.

Sub-Acute Oral Toxicity of a Novel Derivative of Agomelatine in Rats in a Sex-Dependent Manner.

Agomelatine (AGO) is a new type of antidepressant with demonstrated antidepressant effects and a unique modulating circadian rhythm action. However, AGO has hepatotoxicity, which limits its clinical application. In order to develop new drugs that cause less liver injury than AGO, a series of derivatives were synthesized; compound GW117 was screened from derivatives due to its high receptor affinity. This study will investigate its sub-acute oral toxicity profile in rats in a sex-dependent manner. GW117 and AGO was administrated by gavage (200, 400, or 800 mg/kg/day) for 28 days. Hematological, biochemical tests, organ weights, histopathological examinations were carried out, the results showed that AGO and GW117 had adverse effects on platelet, liver and kidney, and had sex-differences in some indicators. Hematological tests showed that AGO and GW117 reduced the platelet count in male animals but had no effect in females. AGO increased plasma alanine aminotransferase (ALT) and total bilirubin in male animals, and GW117 had no effect on these two indicators. For females, AGO moderately elevated ALT, alkaline phosphatase (ALP), and total bilirubin, while GW117 only elevated ALP slightly. Two drugs could increase liver weight and coefficient, and cause liver pathological injury, including hepatic sinusoidal dilatation, hepatocyte fatty deposition and dotted cell necrosis in two genders. AGO caused mild to moderate hepatocyte and hepatobiliary injury in both genders, while only a mild hepatobiliary injury was caused by GW117 in females. Renal function tests showed that both drugs can increase blood urea nitrogen levels in males, while AGO, but not GW117, can slightly increase blood creatinine and urea nitrogen in females. The kidney weight and coefficient could be significantly increased by two drugs in males, and by AGO medium and GW117 high and low doses in females. The kidney pathological damage was mainly characterized by tubule dilatation, a thinning of the renal cortex. Kidney damage caused by GW117 was less than that of AGO, and there was no sex-difference. In summary, GW117 can cause mild liver and kidney damage in both genders, as well as mild platelets reduction in males, while degree of damage is less severe than AGO. Therefore, as an excellent derivative, GW117 deserves further development as an antidepressant.

Allium porrum and Bauhinia Variegata Mitigate Acute Liver Failure and Nephrotoxicity Induced by Thioacetamide in Male Rats.

The present work has been designed to investigate the hepatoprotective and renoprotective efficiency of alcoholic extract of Allium porrum and Bauhinia variegata leaves in thioacetamide-induced toxicity in adult Wistar rats. Allium porrum leaf extract, Bauhinia variegata leaf extract and their combinations were orally administered for 14days then TAA (300mg/kg) i.p. was injected once and the rats were sacrificed 2days later. Plasma AST, ALT, GGT, total bilirubin, creatinine, urea, uric acid, triglyceride, cholesterol, HDL and LDL were measured. Liver MDA, GSH, CAT, SOD and TNF-α were evaluated. Histological examination was performed. The rats treated with TAA showed a significant increase in AST, ALT, GGT, total bilirubin, creatinine, urea, uric acid, total, triglyceride, cholesterol and HDL while it led to a significant decrease in protein and HDL. The treatment of rats with TAA resulted in a significant decrease of the hepatic GSH, SOD and CAT and a significant elevation of MDA and TNF-α. Allium porrum and Bauhinia variegata extracts alleviated the toxic effects of TAA on the liver and the kidney. In conclusion, treatment with Allium porrum and Bauhinia variegata extracts and their combination reduced deleterious effects of TAA on liver through antioxidant and anti-inflammatory properties.

Bilirubin and migraine: critical review of the literature

We read with interest the recent article published by Peng et al . (1), who provided a comprehensive overview on the multiple clinical usefulness of measuring total bilirubin in serum or plasma. Among the various potential applications, the authors highlighted that total bilirubin was found to be lower in patients with migraine than in those without, a conclusion that was supported by a cross-sectional study published by the lead author of the review article (2).

Evaluation of Serum Status of Biochemical Indices of Liver Injury and Oxidative Stress in Rats Exposed to Warri River Levels of Pb and Other Identified Metallic Co Pollutants

This study investigated serum status of biochemical indicators of liver injury and oxidative stress in rats exposed to Warri River level of lead(Pb) alone and in the presence of metallic co-pollutants. A total of 55 albino rats (of Wistar strain) weighing an average of 150.00± 09.00g, divided into 11 groups were used for the study. Groups I and II represented the deionized and Pti borehole water controls, while groups III- XI represented the test rat groups orally treated with water containing laboratory reconstituted Warri River Pb level on one hand and in the presence of laboratory reconstituted identified metallic co-pollutants including Fe, Ca, Cu, Mn, Mg, Zn via water on the other hand. The serum biochemical –hepatotoxic indices investigated were liver/body wt. ratios, body wt. change, lipid per oxidation products, plasma ALT and AST, plasma and liver alkaline phosphatase activities, plasma catalase and superoxide dismutase activities, plasma total and conjugated bilirubin level, plasma and urine glucose concentration, and plasma and urine total protein concentration. Our findings revealed an overall significant (P&lt;0.05) decrease in liver/body wt ratios and body wt change , significant (P&lt;0.05) increase in plasma ALT and AST activities, induced ALP and ACP activities, increase in SOD and catalase activities, increased plasma and urine bilirubin concentrations, decreased plasma and increased urine total protein concentrations, increased Malondialdehyde (MDA) levels, while plasma and urine glucose levels were elevated in the groups of rats exposed to Pb only, Pb + Cu, Pb + Fe and Pb + Zn, Pb + All metallic co-pollutants, and river water relative to their respective controls (deionized water and Pti tap water groups). There was a significant (P&lt;0.05) reversal of the above parameters in the groups of rats exposed to Pb + Ca, Pb + Mn, Pb + Mg. There was also a difference in liver/weight ratio, body wt. change and all the other parameters evaluated in this study, between groups of rats treated with Warri river water relative to the laboratory reconstituted water, although the changes were not significant (P&gt;0.05). Our findings revealed that, the presence of Ca, Mg and Mn in the river water significantly (P&lt;0.05)) reversed the induced activities of ALT, AST, ACP and ALP by Pb and some identified metallic co pollutants like Cu, Fe and Zn. This study also revealed the possibility of significant (P&lt;0.05) decrease in the activities of superoxide dismutase (SOD), catalase , plasma total and direct bilirubin and lipid per oxidation products of rats exposed to Warri River level of Pb in the presence of Ca, Mg and Mn relative to the Pb only group.

Doppler myocardial performance index combined with plasma B-type natriuretic peptide levels as a marker of cardiac function in patients with decompensated cirrhosis.

Background:In chronic liver diseases, cirrhosis ranks as the 14th highest death cause worldwide, developing into decompensated cirrhosis. A potential and feasible technique in assessing cardiac function is urgent. This study explores if the Doppler myocardial performance (Tei) index combined with the plasma B-type natriuretic peptide (BNP) levels can assess cardiac function in patients with decompensated cirrhosis.Methods:A total of 140 individuals were selected in the study and were classified into 3 groups: control group (n = 40, healthy individuals), compensated cirrhosis group (n = 50), and decompensated cirrhosis group (n = 50). Plasma BNP levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and albumin (ALB) were identified by an enzyme-linked immunosorbent assay (ELISA). The correlation of Tei index between left ventricle (LV) and right ventricle (RV) as well as plasma BNP levels with cardiac function was assessed using a Pearson test analysis. All patients were subjected to this experiment for 1 year to analyze the relationship between Tei index and plasma BNP levels in prognosis of decompensated cirrhosis patients.Results:Patients with decompensated cirrhosis showed significantly elevated levels of ALT, AST, and TBIL level in contrary to a reduced ALB level. Cirrhosis patients also showed a significantly reduced ejection fraction (ET) index, but an increase in isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), Tei index, and plasma BNP levels in comparison to healthy individuals. ICT, IRT, Tei index, and plasma BNP levels were elevated in decompensated cirrhotic patients as opposed to compensated cirrhotic patients. These results indicate a positive correlation of both Tei index and plasma BNP levels with cirrhosis and its progression. Tei index and plasma BNP levels are positively associated with Child–Pugh classification and negatively correlated with both cardiac function and prognosis in patients suffering from decompensated cirrhosis.Conclusion:The study provided evidence supporting the correlation of Tei index and plasma BNP levels in decompensated cirrhotic patients with cardiac function, highlighting a potential value for evaluation.

Evaluation of biochemical parameters and oxidative stress in sheep naturally infected with Dicrocoelium dendriticum and hydatid cysts

The purpose of the study was to investigate the lipid peroxidation and antioxidant status as well as biochemical profile in sheep naturally infected with Dicrocoelium dendriticum and hydatid cysts. Ten sheep naturally infected with D. dendriticum, 10 sheep naturally infected with hydatid cysts, and 10 healthy sheep were used. The blood and visceral organs of sheep brought to a slaughterhouse in the region of Kırıkkale were checked for D. dendriticum and hydatid cysts. Plasma total protein, albumin, total bilirubin, total cholesterol, Ca, Mg, inorganic P, Cu, Zn, vitamin A, vitamin C, vitamin E, ß-carotene, AST, ALT, GGT, ALP, erythrocyte MDA levels, and SOD and CAT activities were detected. Erythrocyte MDA, plasma total bilirubin levels, and AST and ALP activities were increased while total protein and vitamin A levels were decreased in sheep infected with parasites. Erythrocyte SOD activities were decreased in D. dendriticum group, and CAT activities were decreased in the hydatid cyst group and D. dendriticum group. Total bilirubin levels were increased and total protein levels were decreased in sheep infected with parasites. These results suggest that endoparasitic infections such as D. dendriticum and hydatid cysts cause oxidative stress and change some biochemical parameters in sheep.

Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats

Quetiapine is an atypical antipsychotic drug used for treatments of patients with schizophrenia. Although hepatotoxic effects related to quetiapine treatment were reported in a few studies, potential hepatotoxicity of this drug was not identified clearly. Therefore, it was aimed to evaluate possible hepatotoxic effects of quetiapine by oral administration of this drug at 10 and 20 mg/kg doses to rats for 30 days in our study. For this purpose, plasma aspartate aminotransferase, alanine aminotransferase, total bilirubin and direct bilirubin levels as markers of hepatotoxicity were determined and histopathological examination was performed in liver tissues. According to our results, serum aspartate aminotransferase and alanine aminotransferase levels were significantly increased in quetiapine-administered groups, whereas total and direct bilirubin levels were significantly increased in high dose group. Histopathological examination of liver tissue indicated that necrotic areas were observed in 10 mg/kg quetiapine-administered group whereas necrotic areas were present and sinusoidal dilatation was observed in 20 mg/kg quetiapine-administered group. According to these results, we concluded that quetiapine may induced hepatotoxic effects in rats, dose-dependently.

“M+N” theory and UV–Vis-NIR transmission spectroscopy used in quantitative analysis of total bilirubin

As a typical representative of complex solution, accurate and rapid determination of blood biochemical values has not only clinical application value, but also high academic research significance. In this paper, the total bilirubin in plasma was taken as the measurement object to prove that the multi-band spectra can refine the analytical precision. Based on the “M+N” theory, combination of ultraviolet spectrum, visible spectrum and near-infrared spectrum was used in modeling. The analytical precision is obviously improved compared with that of single-band modeling, when the same calibration and prediction set were selected in two models. For calibration set and prediction set in visible spectrum modeling, the correlation coefficient is 0.94 and 0.76 respectively; the root mean square error is 1.55 and 19.78 respectively. The correlation coefficient of the joint modeling of UV–vis-NIR is 0.99, and the root mean square error is significantly reduced to 0.47 for the calibration set. And for the prediction set, the correlation coefficient and the root mean square error are 0.86 and 2.56. The results proved the “M+N” theory can improve the analytical accuracy of complex solution.

Blood parameters in fattening pigs from two genetic types fed diet with three different protein concentrations.

The study aimed to evaluate possible differences between two genetic groups (GG) of pigs, fed diets varying in dietary CP level, in hematological and biochemical plasma profiles. The study was carried out in an experimental farm and involved 36 barrows (average BW 129 ± 11 kg) from two GG: group A (18 Italian Duroc boars × Italian Large White sows) and group D (18 DanBred Duroc), fed three experimental diets: a conventional diet and two low-protein diets (LP1 and LP2). A digestibility/balances trial was carried out on 12 pigs A and 12 pigs D that were housed individually in metabolic cages during four digestibility/balances periods. The experimental design was a factorial design, with 3 diets × 2 GG × 4 periods. The experiment lasted 56 d. Blood was sampled from jugular vein in the morning before feed distribution from all barrows in pens at the start and the end of the experimental period; a supplementary blood sample was collected from the 24 pigs at the end of the four digestibility periods (six pigs per period). Blood was analyzed for hematological and biochemical parameters and serum protein profile using automated analyzers. The GG D showed lower white blood cells (WBC), lymphocyte, and monocyte counts than A group. The GG affected several plasma metabolite concentrations: triglycerides, creatinine, Cl, Fe, alkaline phosphatase, and tartrate-resistant acid phosphatase activities were higher in D groups, while urea, albumin, Ca, Na, total bilirubin, and albumin as percentage of total protein were lower than A group. On the contrary, the dietary protein level neither affects WBC nor their populations; only a trend was reported for erythrocytes (red blood cell) and platelets. The diet affected only plasma urea and total bilirubin concentrations.