Markers Of Liver Damage Research Articles

Study Analysis of Total Bilirubin Levels on Mortality in COVID-19 Patients: A Single Center Observational Study at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Coronavirus Disease 2019 (COVID-19) is caused by a positive single-stranded RNA virus. The clinical manifestations of COVID-19 are not only dominated by respiratory tract symptoms but can also show symptoms of liver damage in severe COVID-19 patients. Liver damage that occurs can cause acute liver failure and result in death. Examination of liver damage marker parameters such as total bilirubin needs to be carried out as mortality increases in COVID-19 patients. This study aims to determine the relationship between total bilirubin levels and mortality in COVID-19 patients. Methods: Cross-sectional analytical research was conducted on 40 COVID-19 patients treated at Dr. M. Djamil General Hospital Padang from July to December 2021. Examination of total bilirubin levels using the colorimetric diazo method. Bivariate analysis used the Mann-Whitney test to see the relationship between total bilirubin levels and mortality. Results: The average age of the research subjects was 61.85 (1.40) years, with 65% men and 35% women. The mortality percentage in COVID-19 patients is 65%. The median total bilirubin level was 1.95 (0.5-2.8) mg/dL. The relationship between total bilirubin levels and mortality in COVID-19 patients was found to have a p-value of <0.001. The study results showed that the median total bilirubin level in COVID-19 patients who died was relatively higher, namely 2.20 (1.4-2.8) mg/dL, compared to those who did not die, namely 0.70 (0.5-1. 6) mg/dL. Conclusion: The results of this study show that there is a relationship between total bilirubin levels and mortality in COVID-19 patients.

Optimization of methods for intrasplenic administration of human amniotic epithelial cells in order to perform safe and effective cell-based therapy for liver diseases

In animal experimental models the administration of stem cells into the spleen should ensure high effectiveness of their implantation in the liver due to a direct vascular connection between the two organs. The aim of this study was to update the methods of experimental intrasplenic cell transplantation using human amniotic epithelial cells (hAECs) which are promising cells in the treatment of liver diseases. BALB/c mice were administered intrasplenically with 0.5, 1, and 2 million hAECs by direct bolus injection (400 µl/min) and via a subcutaneous splenic port by fast (20 μl/min) and slow (10 μl/min) infusion. The port was prepared by translocating the spleen to the skin pocket. The spleen, liver, and lungs were collected at 3 h, 6 h, and 24 h after the administration of cells. The distribution of hAECs, histopathological changes in the organs, complete blood count, and biochemical markers of liver damage were assessed. It has been shown that the method of intrasplenic cell administration affects the degree of liver damage. The largest number of mice showing significant liver damage was observed after direct administration and the lowest after slow administration through a port. Liver damage increased with the number of administered cells, which, paradoxically, resulted in increased liver colonization efficiency. It was concluded that the administration of 1 × 106 hAECs by slow infusion via a subcutaneous splenic port reduces the incidence of complications at the expense of a slight decrease in the effectiveness of implantation of the transplanted cells in the liver.

Trimethylamine N-oxide ameliorates hepatic damage including reduction of hepatic bile acids and cholesterol in Fxr-null mice

There are conflicting animal experiments on the effect of trimethylamine N-oxide (TMAO), the dietary metabolite, on non-alcoholic fatty liver disease (NAFLD). This study aims to determine the effect of TMAO on NAFLD. A diet containing 0.3% TMAO was fed to farnesoid X receptor (Fxr)-null mice, a model of NAFLD, for 13 weeks. Fxr-null mice fed TMAO showed significant reductions in liver damage markers but not wild-type mice. Hepatic bile acid and cholesterol levels were significantly decreased, and triacylglycerol levels tended to decrease in TMAO-fed Fxr-null mice. Changes in mRNA levels of hepatic bile acid and cholesterol transporters and synthetic enzymes were observed, which could explain the decreased hepatic bile acid and cholesterol levels in Fxr-null mice given the TMAO diet but not in the wild-type mice. These results suggest that TMAO intake ameliorates liver damage in Fxr-null mice, further altering bile acid/cholesterol metabolism in an FXR-independent manner.

Protective Effects of Lycium ruthenicum Murray against Acute Alcoholic Liver Disease in Mice via the Nrf2/HO-1/NF-κB Signaling Pathway.

Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18-21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RT‒qPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1β expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.

Silibinin's Effects against Methotrexate-Induced Hepatotoxicity in Adjuvant-Induced Arthritis Rat Model.

Methotrexate (MTX) is the first drug of choice to treat several diseases, including rheumatoid arthritis. However, its administration is accompanied by severe side effects, most commonly hepatotoxicity. Hence, alternative therapies with a lower toxicity and fewer side effects are needed. This study aimed to investigate the antioxidant and hepatoprotective effects of silibinin (SIL, natural agent) against MTX-induced hepatotoxicity in an adjuvant-induced arthritis (AIA) rat model. Arthritic rats were treated with SIL (100 mg/kg) and/or methotrexate (2 mg/kg). Non-arthritic rats, arthritic untreated rats, and arthritic rats who received the vehicle were followed in parallel. SIL alleviated the systemic consequences of arthritis by restoring lost weight, decreasing the erythrocyte sedimentation rate, and ameliorating joint damage, which was evident both micro- and macroscopically. Additionally, SIL prevented the histopathological alterations in the liver and significantly reduced the liver damage caused by MTX and AIA, as shown by a decrease in the markers of liver damage (ALT and AST). Furthermore, SIL relieved the oxidative stress induced by AIA and MTX in liver tissue by decreasing the lipid peroxidation (MDA) levels and enhancing the antioxidant defense system (GSH levels; catalase and superoxide dismutase (SOD) activities). In conclusion, our results suggest that SIL is a potent antioxidant and hepatoprotective agent in arthritic rats. It markedly attenuated the progression and severity of the arthritic disease and eased the oxidative stress in liver tissue by improving the pro-oxidant/antioxidant balance.

Associations of hypertension with clinical and instrumental characteristics in the ukrainian cohort of patients hospitalized for COVID-19

long COVID-19 syndrome causes sustained limitations in activity and work capacity in a significant proportion of convalescents, the risk of which is higher among patients who required hospitalization. Phenotyping of COVID-19 survivors based on the most common comorbidities’ role in shaping the risks of the acute phase endpoints and development of post-covid syndrome can be used to improve the efficacy of predicting the course of the disease. To study the associations of hypertension (HT) with the clinical features of acute COVID-19 in hospitalized patients, severity of residual functional disorders and pulmonary affection by the time of discharge. Material and methods. 221 hospitalized patients with COVID-19 (age 53,4 ± 13,6 years, 53% female) were examined 1-2 days before discharge. The study protocol included interview and analysis of medical documentation to retrospectively extract the anamnestic data and clinical features of the acute phase; lung ultrasound, reactive hyperemia test of the brachial artery, and a 6-minute walk test. Results. The most frequently identified comorbidities in the study cohort were HT, obesity, and type 2 diabetes, which were present in 40%, 38%, and 10% of participants, respectively. Hypertensive patients were older (57,8 ± 11,8 vs 50,7 ± 13,9 years, р < 0,001), had higher BMI (31,7 ± 5,3 vs 31,7 ± 5,3 кг/м2, р < 0,001), higher prevalence of obesity (59% vs 25%, p < 0,001) and type 2 diabetes (21% vs 2%, p < 0,001) compared to normotensive participants, but were characterized by comparable laboratory indices, parameters of pulmonary parenchyma affection (by CT scan and lung ultrasound), endothelial function, SpO2 levels during the acute phase of the disease and by the time of discharge, as well as age- and anthropometric parameters-adjusted 6-minute walk distance (67,4 ± 10,5 % vs 69,5 ± 13,6 %, p > 0,05). Hypertensive patients hospitalized for COVID-19 were characterized by older age, higher prevalence of obesity and type 2 diabetes compared to normotensive participants but did not differ in their laboratory profile (including markers of systemic inflammation, prothrombotic activation, renal function, and liver damage), levels of pulmonary affection by CT and lung ultrasound, and endothelium-dependent vasodilatation in a reactive hyperemia test of the brachial artery. The observed decrease in the 6-minute walk distance in patients with HT was explained by differences in age and anthropometric parameters.

Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia.

Long non-coding RNA (lncRNA) genes represent a large class of transcripts that are widely expressed across species. As most human lncRNAs are non-conserved, we recently employed a unique humanized liver mouse model to study lncRNAs expressed in human livers. We identified a human hepatocyte-specific lncRNA, hLMR1 (human lncRNA metabolic regulator 1), which is induced by feeding and promotes hepatic cholesterol synthesis. Recent genome-wide association studies (GWAS) found that several single-nucleotide polymorphisms (SNPs) from the hLMR1 gene locus are associated with blood lipids and markers of liver damage. These results suggest that dietary and genetic factors may regulate hLMR1 to affect disease progression. In this study, we first screened for nutritional/hormonal factors and found that hLMR1 was robustly induced by insulin/glucose in cultured human hepatocytes, and this induction is dependent on the transcription factor SREBP1. We then tested if GWAS SNPs genetically linked to hLMR1 could regulate hLMR1 expression. We found that DNA sequences flanking rs9653945, a SNP from the last exon of the hLMR1 gene, functions as an enhancer that can be robustly activated by SREBP1c depending on the presence of rs9653945 major allele (G). We further performed CRISPR base editing in human HepG2 cells and found that rs9653945 major (G) to minor (A) allele modification resulted in blunted insulin/glucose-induced expression of hLMR1. Finally, we performed genotyping and gene expression analyses using a published human NAFLD RNA-seq dataset and found that individuals homozygous for rs9653945-G have a higher expression of hLMR1 and risk of NAFLD. Taken together, our data support a model that rs9653945-G predisposes individuals to insulin/glucose-induced hLMR1, contributing to the development of hyperlipidemia and NAFLD.

Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease

Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.

131 Selenium-form effects on hepatic function and selenoprotein mRNAs in the early pregnant heifer

Abstract Selenium (Se) is an integral component of selenoproteins, with effective scavenging of harmful reactive oxygen species (ROS) by selenoproteins necessary to protect cells from oxidative stress. Due to the presence of Se-deficient soils in large portions of the US, including the southeast cow-calf producing states, grazed forages are insufficient in this trace mineral and dietary supplementation is recommended. We have investigated the effects of providing Se in an inorganic form (ISe, the industry standard) versus a 1:1 mixture (MIX) of ISe to organic Se (OSe), and have observed significant effects on luteal function, endometrial function and conceptus development. Herein, our objective was to determine the effect of form of Se on 1) clinical markers of total antioxidant capacity and liver function, and 2) the expression of mRNAs encoding selenoproteins in the liver. Following consecutive 45-d periods of Se-depletion then repletion, Angus-cross heifers were assigned to 90 d of treatment with a vitamin-mineral mix containing 35-ppm Se as ISe or MIX. Heifers were then inseminated at estrus (d 0) with serum collected at d 0, 7 and 17 to quantify albumin, beta-hydroxybutyrate (BHBA) and aspartate aminotransferase (AST). Liver samples were collected at euthanasia on d 17 (n = 6 pregnant heifers per treatment) for the quantification of the relative abundance of 25 selenoprotein mRNAs using qPCR. There was no effect of treatment on circulating albumin (P > 0.05). Hepatocyte-secreted albumin is the most prominent antioxidant in the circulation, with this result suggesting that albumin-driven redox capacity is not sensitive to the form of Se supplied to achieve a Se-adequate status. Systemic concentrations of BHBA and AST were increased (P < 0.05) in MIX- versus ISe-treated heifers at d 7 and 17 of pregnancy. Circulating BHBA is considered a primary indicator of liver function and the hepatic response to increased metabolic demands, whereas increased AST is conventionally considered a marker for liver damage. These results suggest increased demands on the liver in MIX versus ISe-treated heifers, however not at the level indicative of dysfunction or disease. Additionally, the serum concentration of urea nitrogen was quantified and determined to be reduced (P < 0.05) at estrus in MIX- versus ISe-treated heifers, indicative of form-induced changes in hepatic nitrogen metabolism. Targeted qPCR analysis to determine the effect of treatment on the abundance of encoding selenoproteins by mRNA, including the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, was largely unaffected by treatment, with only the abundance of mRNA encoding Selenoprotein V tending to differ (P = 0.07) with treatment. Overall, this study revealed form of Se-effects on markers of hepatic health and function, as well as blood urea nitrogen, but did not reveal form of Se-effects on the expression of hepatic selenoproteins mRNAs.

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers.

Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2-15.1 mg/dL; 0.01-0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79-260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug-drug interactions leading to hepatotoxicity. Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

Smoke Signals: Unraveling the Link between Cigarette Smoking and Serum Liver Markers

Introduction: Cigarette smoking is a major cause of global mortality and morbidity. It exposes the body to many harmful substances, such as cytotoxic, carcinogenic and free radicals, that can damage various organs. This study aims to investigate the effects of different levels of tobacco exposure on liver tissue, by measuring some serum biochemical markers of liver function.
 Materials and Methods: The project conducted at T.N.M.C Mumbai from January to December 2021 involved 60 male participants (18–35 years old), divided into smokers (30) and non-smokers (30). Smokers had varying smoking durations (1-5 years). Excluded participants with diseases affecting liver enzymes. Groups were age-matched for analysis. Smokers defined as those smoking >20 cigarettes daily for >1 month. Collected 5.0 ml venous blood, processed in heparinized tubes, and centrifuged for plasma separation. Enzymes SGOT, SGPT, ALP, Total Bilirubin, Direct Bilirubin were measured, and statistical analysis revealed significant differences.
 Results: In the study, age comparison between smokers and non-smokers showed no significant difference (p = 0.71). However, smokers exhibited significantly higher mean serum concentrations of SGOT and SGPT compared to non-smokers (p = 0.002 and p < 0.0001, respectively). Smokers also had elevated levels of ALP and total bilirubin with mean differences of 16.3 IU/L and 0.392 mg/dl, supported by 95% confidence intervals (6.72, 26.18) and (0.28, 0.504) and p values of 0.003 and 0.0004, respectively. No significant difference was observed in direct bilirubin levels (mean difference: 0.084 mg/dl, 95% CI: 0.065, 0.103, p = 0.191)
 Conclusion: In summary, the study suggests a correlation between smoking and elevated serum levels of liver enzymes and damage markers, indicating a potential adverse impact on liver function and increased susceptibility to liver diseases.

Detecting the risk for fatty liver, MASH, and insulin resistance using different indexes and markers of liver damage in young adults from West Mexico

Detecting the risk for fatty liver, MASH, and insulin resistance using different indexes and markers of liver damage in young adults from West Mexico

Association between serum trace element, mineral, and amino acid levels with non-alcoholic fatty liver disease (NAFLD) in adult women

The objective of the present study is assessment of serum trace element and amino acid levels in non-alcoholic fatty liver disease (NAFLD) patients with subsequent evaluation of its independent associations with markers of liver injury and metabolic risk. Materials and methods140 women aged 20–90 years old with diagnosed NAFLD and 140 healthy women with a respective age range were enrolled in the current study. Analysis of serum and hair levels of trace elements and minerals was performed with inductively-coupled plasma mass-spectrometry (ICP-MS). Serum amino acid concentrations were evaluated by high-pressure liquid chromatography (HPLC) with UV-detection. In addition, routine biochemical parameters including liver damage markers, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT), were assessed spectrophotometrically. ResultsThe findings demonstrated that patients with NAFLD were characterized by higher ALT, GGT, lactate dehydrogenase (LDH) and cholinesterase (CE) activity, as well as increased levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid. NAFLD patients were characterized by reduced serum and hair Co, Se, and Zn levels, as well as hair Cu content and serum Mn concentrations in comparison to controls. Circulating Ala, Cit, Glu, Gly, Ile, Leu, Phe, and Tyr levels in NAFLD patients exceeded those in the control group. Multiple linear regression demonstrated that serum and hair trace element levels were significantly associated with circulating amino acid levels after adjustment for age, BMI, and metabolic parameters including liver damage markers. ConclusionIt is proposed that altered trace element handling may contribute to NAFLD pathogenesis through modulation of amino acid metabolism.

Assessment of thiamylal sodium as a euthanasia drug in mice.

Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals, and injectable anesthetics, particularly barbiturate derivatives, are widely used due to the rapid onset of unconsciousness induced by these agents. Moreover, pharmaceutical-grade drugs should be used to eliminate undesirable side effects as much as possible. However, in Japan, the sale of pharmaceutical-grade pentobarbital sodium (PB) ended in 2019, and that of secobarbital sodium (SB) ended in 2023, leading to a demand for new pharmaceutical-grade injectable euthanasia drugs. This study evaluates thiamylal sodium (TM), a barbiturate derivative that is available domestically, as a euthanasia agent for mice. The results showed that when administered at dosages of 200 mg/kg or more, TM exhibited effects equivalent to those of PB and SB. In addition, the impact of TM administration on hematological characteristics was examined. In female mice administered TM, decreased blood chloride and calcium levels and increased aspartate aminotransferase and alanine aminotransferase levels, which are markers of liver damage, were observed. These findings suggest that high concentrations of TM may affect renal and liver function. This study revealed that TM is effective as a euthanasia agent at dosages of 200 mg/kg or more. However, considering the potential risks of renal and liver damage due to TM administration, it may be preferable to use alternative euthanasia drugs when these risks could affect the objectives or outcomes of the research.

In Vivo and In Silico Studies of the Hepatoprotective Activity of Tert-Butylhydroquinone.

Tert-butylhydroquinone (TBHQ) is a synthetic food antioxidant with biological activities, but little is known about its pharmacological benefits in liver disease. Therefore, this work aimed to evaluate TBHQ during acute liver damage induced by CCl4 (24 h) or BDL (48 h) in Wistar rats. It was found that pretreatment with TBHQ prevents 50% of mortality induced by a lethal dose of CCl4 (4 g/kg, i.p.), and 80% of BDL+TBHQ rats survived, while only 50% of the BDL group survived. Serum markers of liver damage and macroscopic and microscopic (H&E staining) observations suggest that TBHQ protects from both hepatocellular necrosis caused by the sublethal dose of CCl4 (1.6 g/kg, i.p.), as well as necrosis/ductal proliferation caused by BDL. Additionally, online databases identified 49 potential protein targets for TBHQ. Finally, a biological target candidate (Keap1) was evaluated in a proof-of-concept in silico molecular docking assay, resulting in an interaction energy of -5.5491 kcal/mol, which was higher than RA839 and lower than monoethyl fumarate (compounds known to bind to Keap1). These findings suggest that TBHQ increases the survival of animals subjected to CCl4 intoxication or BDL, presumably by reducing hepatocellular damage, probably due to the interaction of TBHQ with Keap1.

Biological and histological changes and DNA damage in Oreochromis niloticus exposed to oxytetracycline: a potential amelioratory role of ascorbic acid

Antibiotics are crucial in the control of bacterial infections on fish farms. However, the influence of licensed antibiotics on DNA damage, histological changes, and protein differentiation in some farmed fish species is unidentified. The current study aimed to investigate the effect of therapeutic (80 mg/kg body weight/day) and high doses (160 mg/kg body weight/day) of oxytetracycline (OTC) on some biological indices, protein differentiation, histological changes, and DNA damage in Oreochromis niloticus (n = 360; 40 ± 3.5 g) and the potential positive effects of dietary ascorbic acid (AA) and whether it is capable of reducing the deleterious impacts of OTC and working synergistically to increase fish disease resistance and decrease morbidity and mortality rates. In the current study, fish were fed diets with or without OTC (80 or 160 mg/kg body weight/day) and AA (100 mg/kg diet/day) for 28 days, followed by a bacterial stress test with two different virulent strains for 14 days. Treatments include CTR (control; without additives), AA, OTC80, OTC160, OTC80 + AA, and OTC160 + AA. The results revealed that the AA group had the best antioxidative (significant increase in SOD, CAT, and GPx) and immunomodulatory effects (an increase in IgM, nitroblue tetrazolium, and total leucocytic count). Furthermore, the hematological parameters, immune indices (NBT), and antioxidant enzymes were significantly reduced by OTC160 (p ≤ 0.05). The results also showed that OTC160 notably augmented the activity of liver (ALT, AST, and LDH) and kidney (creatinine and urea) damage markers (p ≤ 0.05). OTC160 revealed considerable hepatic and renal tissue damage and significantly higher hepatocyte DNA damage. Pathological changes and DNA damage were directly correlated to the dosage of OTC exposure, where they were more severe in OTC160. OTC80 showed insignificant changes in most parameters. Compared to CTR, the inclusion of AA in the O. niloticus diet significantly restored the biological indices, histological changes, and DNA damage in OTC-treated groups. The morbidity and mortality percentages after bacterial challenge were significantly lower in the OTC80 + AA group, followed by the OTC160 + AA group than in the CTR. These results corroborate the use of AA as a potent antioxidant and immune stimulant and a potential co-adjuvant to OTC in the diet of O. niloticus to reach optimal resistance to disease.

Exploring the Safety of Pllans-II and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy.

The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 "Pllans-II," isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer.

THE REVIEW ARTICLE ON LIVER FUNCTION TEST IN HUMAN BODY

Laboratory Liver function tests (LFT) may be defined as the tests which are useful in the evaluation and treatment of patients with hepatic dysfunction. Theliver is of vital importance in intermediary metabolism, in the detoxification andin the elimination of toxic substances. The biochemical tests are useful in detecting the presence of liver disease. The test are also cheap, non- invasive and widely available and are of value in directing the use of other diagnostic tests such as liver biopsy and imaging. Some of the biochemical markers such asserum Bilirubin, SGPT or Alanine amino transferase (ALT) , SGOT or aspartate amino transferase (AST) , Alkaline phosphatase (ALP), Gamma Glutamyl Transferase (GGT), 5′ nucleotidase, Ceruloplasmin etc. are considered in this article. An isolated or conjugated alteration of biochemical markers of liver damage in patients can challenge the clinicians during the diagnosis of disease related to liver directly or with some other organs.

Sirtuin 1 alleviates alcoholic liver disease by inhibiting HMGB1 acetylation and translocation.

Alcoholic liver disease (ALD) encompasses a spectrum of liver disorders resulting from prolonged alcohol consumption and is influenced by factors such as oxidative stress, inflammation, and apoptosis. High Mobility Group Box 1 (HMGB1) plays a pivotal role in ALD due to its involvement in inflammation and immune responses. Another key factor, Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, is known for its roles in cellular stress responses and metabolic regulation. Despite individual studies on HMGB1 and SIRT1 in ALD, their specific molecular interactions and combined effects on disease advancement remain incompletely understood. Alcohol-induced liver injury (ALI) models were established using HepG2 cells and male C57BL/6 mice. HMGB1 and SIRT1 expressions were assessed at the mRNA and protein levels usingreverse transcription-quantitative polymerase chain reaction, western blot, and immunofluorescence staining. The physical interaction between HMGB1 and SIRT1 was investigated using co-immunoprecipitation and immunofluorescence co-expression analyses. Cellular viability was evaluated using the CCK-8 assay. In patients with clinical ALI, HMGB1 mRNA levels were elevated, while SIRT1 expression was reduced, indicating a negative correlation between the two. ALI models were successfully established in cells and mice, as evidenced by increased markers of cellular and liver damage. HMGB1 acetylation and translocation were observed in both ALI cells and mouse models. Treatment with the SIRT1 agonist, SRT1720, reversed the upregulation of HMGB1 acetylation, nuclear translocation, and release in the ethyl alcohol (EtOH) group. Furthermore, SIRT1 significantly attenuated ALI. Importantly, in vivo binding was confirmed between SIRT1 and HMGB1. SIRT1 alleviates HMGB1 acetylation and translocation, thereby ameliorating ALI.

Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis.

Human African trypanosomiasis (HAT) and schistosomiasis are neglected parasitic diseases found in the African continent. This study was conducted to determine how primary infection with Schistosoma mansoni affects HAT disease progression with a secondary infection with Trypanosoma brucei rhodesiense (T.b.r) in a mouse model. Female BALB-c mice (6-8 weeks old) were randomly divided into four groups of 12 mice each. The different groups were infected with Schistosoma mansoni (100 cercariae) and Trypanosoma brucei rhodesiense (5.0 × 104) separately or together. Twenty-one days after infection with T.b.r, mice were sacrificed and samples were collected for analysis. The primary infection with S. mansoni significantly enhanced successive infection by the T.b.r; consequently, promoting HAT disease severity and curtailing host survival time. T.b.r-induced impairment of the neurological integrity and breach of the blood-brain barrier were markedly pronounced on coinfection with S. mansoni. Coinfection with S. mansoni and T.b.r resulted in microcytic hypochromic anemia characterized by the suppression of RBCs, hematocrit, hemoglobin, and red cell indices. Moreover, coinfection of the mice with the two parasites resulted in leukocytosis which was accompanied by the elevation of basophils, neutrophils, lymphocytes, monocytes, and eosinophils. More importantly, coinfection resulted in a significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, creatinine, urea, and uric acid, which are the markers of liver and kidney damage. Meanwhile, S. mansoni-driven dyslipidemia was significantly enhanced by the coinfection of mice with T.b.r. Moreover, coinfection with S. mansoni and T.b.r led to a strong immune response characterized by a significant increase in serum TNF-α and IFN-γ. T.b.r infection enhanced S. mansoni-induced depletion of cellular-reduced glutathione (GSH) in the brain and liver tissues, indicative of lethal oxidative damage. Similarly, coinfection resulted in a significant rise in nitric oxide (NO) and malondialdehyde (MDA) levels. Primary infection with S. mansoni exacerbates disease severity of secondary infection with T.b.r in a mouse model that is associated with harmful inflammatory response, oxidative stress, and organ injury.