Increased Liver Enzymes Research Articles

Glucagon receptor modulation: Its role in diabetes care

Abstract The metabolic changes attributable to diabetes are due to both deficiency of insulin as well as excess glucagon (GC). The glucagon receptor (GCGR) is a G protein-coupled receptor. GC is predominantly found in the liver. GC exerts its action both at the GCGR and the glucagon-like peptide receptor (GLP1R). Knockout studies as well as human mutation analysis have indicated therapeutic potential as well as concerns of modulation of the GCGR as a potential target for diabetes therapies. Three approaches to GCGR antagonism—small molecules, monoclonal antibodies, and antisense oligonucleotides—have demonstrated an impressive reduction in HbA1C in preclinical and clinical studies. However, adverse events such as an increase in weight cholesterol liver enzymes and alpha cell hyperplasia have stalled further clinical development. On the other hand, balancing the hyperglycemic effect of glucagon and retaining their beneficial effects, especially with weight loss and decrease in weight loss and hepatic steatosis by use of unimolecular coagonists with GLP1 and GIP have shown considerable promise in clinical trials.

Effect of high-sucrose diet on liver enzymes and serum protein levels of Wistar albino rats

A global change in dietary habits has led to the introduction of sweeteners in foods. This study investigated the effect of concentrations of sucrose on liver enzymes and serum protein levels in Wistar rats. Thirty-five (35) Wistar rats were equally randomized into seven groups and fed with a rat diet mixed with sucrose at concentrations of 10, 20, 40, 60, 80, and 100% w/w, while the control group was fed on a normal diet without sucrose. Their blood samples were analyzed for total protein, albumin, ALT, AST, ALK phosphatase, and gamma-glutamyl transpeptidase (ƔGT) levels. The results indicated that there was a significant (p<0.05) increase in AST (16.00-82.00 µ/L), ALT (44.00-90.80 µ/L), ALK Phos (44.00-90.80 µ/L), and a corresponding decrease in total proteins (69.80-61.39 g/L), albumin (36.00-34.00 g/L) and ƔGT (493.00-191.00 µ/L) levels as the concentration of sucrose increased. Rats fed with sucrose diets had higher levels of AST (39.27 µ/L), ALT (14.50 µ/L), and ALK Phos (68.47 µ/L) than rats fed with normal diets. Therefore, high doses of sucrose can cause increases in serum liver enzymes and total proteins that are suggestive of liver necrosis. Hence, by decreasing the concentrations of sucrose, the liver may be protected.

Thermal Injury to the Subhepatic Appendix Following Percutaneous Ultrasound-Guided Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report.

We present the first documented case of a fistula between the treated zone and the appendix after RFA in a patient with HCC. Contrast-enhanced CT and MRI revealed a subcapsular hepatic nodule with image findings of HCC located adjacent to the ascending colon and cecum. An ultrasound-guided core needle biopsy was subsequently performed to distinguish between hepatic metastasis and HCC. Post-RFA imaging identified a low-attenuating ablated area adjacent to an air-filled appendix. The patient later experienced complications, including increased liver enzymes and an abscess at the ablation site. Imaging revealed a fistulous tract between the RFA zone and the appendix. Over the following months, the patient underwent conservative treatment involving intravenous antibiotics and repeated percutaneous drainage, exhibiting eventual symptom relief and an absence of the fistulous tract upon subsequent imaging. This case highlights the rare complications that can arise during RFA due to peculiar anatomical variations, such as a subhepatic appendix, resulting from midgut malrotation and previous surgery. It is imperative for operators to be cognizant of potential anatomical variations when considering RFA treatment, ensuring comprehensive pre-procedural imaging and post-procedure monitoring. This case also emphasizes the potential viability of nonoperative management in complex scenarios in which surgical interventions pose significant risks.

Pharmacokinetics of cycloheximide in rats and evaluation of its effect as a blocker of intestinal lymph formation

Cycloheximide (CHX) has been used to reduce the flow of intestinal lymph and as a non-surgical tool to study drug absorption via the intestinal lymphatics. Pharmacokinetic information on the agent, and its relationship to effect and toxicity, have not been examined. The goal of this study was to provide pharmacokinetic data and link it to lymph-blocking and toxicological effects. Jugular-vein cannulated (JVC) adult Sprague-Dawley male rats were administered 0.5 mg/kg CHX by oral, intraperitoneal (ip), and intravenous routes followed by blood draws, and CHX was assayed using LC-MS/MS. Another four JVC rats were given peanut oil (2 mL/kg) without and then with CHX to measure effects on lipid absorption as a surrogate indicator of lymph flow. One-week later plasma biochemistry measures were obtained. The results indicated that CHX had a high clearance and volume of distribution, and oral absolute bioavailability of 0.47 with 0.5 mg/kg. CHX was associated with dose- and route-dependent pharmacokinetics. The relative bioavailability after ip doses was over 3. CHX had low plasma protein binding and minor urinary excretion. Metabolism appeared to be occur by oxidation and glucuronidation. Reductions in plasma lipids (24–40 %) were seen after 2.5 mg/kg orally with signs of inflammation and increased liver enzymes persisting for a week after the dose. CHX was associated with a reduction in lipid absorption after oral doses of 2.5 mg/kg, which seems to justify its use as a non-surgical tool to evaluate the lymphatic pathway of absorption of drugs. However, it also possesses hepatotoxicity, which should be taken into consideration in its use.

Recurrent tinea corporis generalisata due to Terbinafine-resistant Trichophyton rubrum strain : Long-term treatment with super bioavailability itraconazole

For more than 30years, an 82-year-old man has been suffering from tinea corporis generalisata in the sense of Trichophyton rubrum syndrome. The patient received long-term treatment with terbinafine. Fluconazole had no effect. There was an increase in liver enzymes with itraconazole. Super bioavailability (SUBA) itraconazole was initially not tolerated. Atherapy attempt with voriconazole was successful, but was stopped due to side effects. The Trichophyton (T.)rubrum strain isolated from skin scales was tested for terbinafine resistance using the breakpoint method and found to be (still) sensitive. Sequencing of the squalene epoxidase (SQLE) gene revealed apreviously unknown point mutation of the codon for isoleucine ATC→ACC with amino acid substitution I479T (isoleucine479 threonine). Long-term therapy with terbinafine 250 mg had been given every 3days since 2018. In addition, bifonazole cream, ciclopirox solution, and occasionally terbinafine cream were used. The skin condition was stable until an exacerbation of the dermatophytosis in 2021. There were erythematosquamous, partly atrophic, centrifugal, scaly, confluent plaques on the integument and the extremities. Fingernails and toenails had white to yellow-brown discoloration, and were hyperkeratotic and totally dystrophic. T.rubrum was cultured from skin scales from the integument, from the feet, from nail shavings from the fingernails and also toenails and detected by PCR. In the breakpoint test, the T.rubrum isolates from tinea corporis and nail samples showed aminimum inhibitory concentration (MIC) of 0.5 µgml-1 (terbinafine resistance in vitro). Sequencing of the SQLE gene of the T.rubrum isolate revealed evidence of afurther point mutation that led to amino acid substitution I479V (isoleucine 479 valine). Long-term therapy was started with SUBA itraconazole: 14days 2 × 1capsule daily, then twice weekly administration of 2 × 50 mg. During breaks in therapy, the mycosis regularly flared up again. Finally, 50 mg SUBA itraconazole was given 5days aweek, which completely suppressed the dermatophytosis. Topically, ciclopirox and miconazole cream were used alternately. In conclusion, in the case of recurrent and therapy-refractory dermatophytoses caused by T.rubrum, terbinafine resistance must also be considered in individual cases. An in vitro resistance test and point mutation analysis of the squalene epoxidase gene confirms the diagnosis. Itraconazole, also in the form of SUBA itraconazole, is the drug of choice for the oral antifungal treatment of these patients.

SAT072 Choline Deprivation Aggravates Hyperglycemia And Fatty Liver In Non-obese Streptozocin-induced Diabetic Rats

Abstract Disclosure: C. Liapi: None. A. Kyriakaki: None. H. Al Humadi: None. R. Al-Saigh1: None. A. Al Humadi: None. A. Lazaris: None. Background: Choline deprivation (CD) is an established model of steatohepatitis. There is a strong association between non-alcoholic fatty liver disease and diabetes mellitus that has a significant impact on the global health system. The combined state of CD and diabetes can resemble common cases in clinical practice including parenteral nutrition, pregnancy, chronic liver disease malnutrition and/ or alcoholism in diabetic individuals. The aim of this study was to investigate the effects of choline deprivation on glycemic control, insulin signaling pathway and lipid metabolism in non-obese streptozocin-induced diabetic rats. Methods: Thirty-two male adult Wistar rats were divided into four groups; control, diabetes (DM), choline-deprived diet (CDD), and combined group (DM+CDD); DM was induced by intraperitoneal streptozotocin administration. Body weight, fasting blood glucose and plasma insulin levels, lipid profile, liver biochemistry, liver histopathology and gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters 2 & 4 (GLUT-2 & -4) in hepatic tissue, were assessed. Results: The combination group (CDD+DM) showed a significant increase in blood glucose associated with a significant decrease in plasma insulin level and evidence of dyslipidemia with a significant increase in liver enzymes, histopathology showed extensive micro- and macrovesicular steatosis and a significant decrease in weight gain versus the control, CDD and DM group. A significant increase was observed in gene expression of IR, IRS-1, GLUT-2, and GLUT-4 in all the experimental groups versus the control. Conclusion: The combination of choline deficiency and diabetes has drawn some new scenarios on insulin and some hepatic metabolic pathways: (i) plasma insulin resistance with progressive hyperglycemia and hyperlipidemia.(ii) attenuation of hepatic insulin resistance or sensitization of insulin signaling pathways in the liver, due to the hepatotoxic effects of choline deficiency that could ultimately simulate features of the metabolic syndrome, and (iii) experimentally simulation of metabolic conditions seem to act synergistically, leading to poor glycemic control along with aggravation of hepatic steatosis. Presentation: Saturday, June 17, 2023

Effectiveness of curcumin nanoparticles in rat liver fibrosis caused by thioacetamide.

Although curcumin possesses anti-inflammatory, antioxidant, and cytoprotective qualities, its low absorption limits its medicinal uses. Before examining how curcumin influenced rats' liver fibrosis when thioacetamide (TAA) was produced, the current study employed nanoparticles (NPs) to improve curcumin bioavailability. Sixty mature rats were separated into six groups (Group 1, control; Group 2, curcumin; Group 3, curcumin nanoparticles; Group 4, TAA; Group 5, TAA + curcumin; Group 6, TAA + curcumin NPs). TAA administration caused considerable increases in serum liver enzymes associated with a remarkable depletion in the levels of albumin and total protein relative to the control. In addition, a significant elevation in malonaldehyde (MDA) level with a significant depletion in the antioxidant enzymes activity was detected. Also, TAA had a significant effect on the inflammation markers represented by the elevation in tumor necrosis factor (TNFα) and DNA damage. Administration of curcumin or curcumin NPs in TAA-intoxicated rats significantly (p < .001, p < .0001) alleviates liver injury by correcting antioxidant status, inflammatory markers, and oxidative stress. The results of comparing TAA-intoxicated rats treated with curcumin NPs to TAA-intoxicated rats treated with bulk curcumin revealed that the ameliorative effect of nanocurcumin was stronger. These observations concluded that nanoparticle formulation can increase curcumin bioavailability and solubility, enhancing its antioxidant and anti-inflammatory efficiency, resulting in greater potential against thioacetamide-induced hepatotoxicity in rats.

Panax ginseng ameliorates hepatorenal oxidative alterations induced by commercially used cypermethrin in male rats: experimental and molecular docking approaches

Cypermethrin (CYP) is a synthetic pyrethroid utilized as an insecticide in agriculture and various pest eradication programs. However, it induces numerous health hazards for animals and humans. Therefore, the current study used Panax ginseng root extract (ginseng) to reduce the hepatorenal damage caused by commercially used CYP. Thirty-two male Wistar albino rats were distributed into control, ginseng (300 mg/kg B.W/day), CYP (4.67 mg/kg B.W.), and Ginseng+CYP (rats received both CYP and ginseng). All treatments were administered orally for 30 consecutive days. Cypermethrin induced harmful effects on hepatic and renal tissues through a substantial decline in body weight in addition to a considerable increase in liver enzymes, functional renal markers, and cholesterol. Also, CYP significantly decreased acetylcholinesterase (AChE) activity and increased pro-inflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)). Moreover, a marked increase in malondialdehyde level with a significant drop in reduced glutathione level and total superoxide dismutase (T-SOD) and catalase (CAT) activities was reported in the CYP group in kidney and liver tissues. Additionally, CYP exhibited affinities to bind and inhibit AChE and antioxidant enzymes (T-SOD and CAT) in rats following the molecular docking modeling. The apparent hepatorenal oxidative damage was linked with obvious impairments in the liver and kidney histoarchitecture, immunohistochemical staining of B cell lymphoma-2 (Bcl-2), and caspase-3 proteins. Ginseng reduced CYP’s oxidative alterations by repairing the metabolic functional markers, improving antioxidant status, reducing the inflammatory response, and enhancing the molecular docking evaluation. It also ameliorated the intensity of the histopathological alterations and improved the immunohistochemical staining of Bcl-2 and caspase-3 proteins in the liver and kidney tissues. Finally, concomitant oral administration of ginseng mitigated CYP-prompted hepatorenal damage through its antioxidant, anti-inflammatory, and anti-apoptotic potentials.Graphical

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy

We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (-1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P< 0.05). There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.

COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.

Clinicopathological characteristics and key therapeutic options for liver involvement with vasculitis

Vasculitis, involving any levels of vessels throughout the body, has variable nonspecific clinical presentation and complicated classification, hence, the diagnose is difficult. The liver is not the major organ involved, so it is prone to overlook vasculitis-associated liver injuries. The main manifestations of vasculitis involving the liver include abnormal liver biochemistry test (mainly increase of cholestatic liver enzymes), portal hypertension, and hepatic occupying lesions. Treatment principles are primarily directed at systemic immunosuppressive therapy for vasculitis. This review summarized the classification of vasculitis, major presentations of liver involvement in vasculitis, and the principles of treatment, to improve the awareness of the rare vascular diseases.

Intensive Care Management of Eclampsia with HELLP Syndrome: A Case Report

Background: The incidence of HELLP syndrome is approximately 0.1-1% of all pregnant women and 5.5% of patients admitted to the ICU. Hemolysis, elevated liver enzymes, and thrombocytopenia are the characteristics of HELLP syndrome.&#x0D; Case Presentation: A 38-year-old patient with diagnosed G4P3A0L3 31-32 weeks of preterm pregnancy + eclampsia on MgSO4 regimen, HELLP syndrome + twice previous Sectio cesarean + breech presentation. On physical examination, the general condition was blood pressure 199/103 mmHg. The results of laboratory tests post-op were hemoglobin 7,1 g/dL, leukocytes 15.930, hematocrit 24%, and platelets 38,000. The results of other laboratory tests showed decreased albumin levels (Alb 2,4), increased levels of total bilirubin 14,7, direct bilirubin 10,8 and indirect bilirubin 3,9, increased liver enzyme SGOT 2001 SGPT 513.&#x0D; Conclusion: HELLP syndrome is a threatening clinical problem. Appropriate and adequate management, especially in the Intensive care unit, is needed to prevent severe complications to reduce morbidity and mortality rates in patients with HELLP syndrome.

Antiviral and immunoregulatory effects of curcumin on coxsackievirus B3-infected hepatitis

Fulminant hepatitis is a life-threatening complication of coxsackievirus B (CVB) 3 infections. The condition may deteriorate to disseminated intravascular coagulopathy with markedly increased liver enzymes, inflammatory cytokines, and chemokines, which significantly induce local and systemic inflammation. Curcumin exhibits anti-inflammatory and antiviral characteristics in inflammatory and infectious diseases. Here we determined effects of curcumin on viral replications, cytokine and chemokine expressions, and liver damage in CVB3-infected Huh-7 cells. The mouse-adapted CVB3 strain was used to investigate the antiviral and anti-inflammatory effects of curcumin on CVB3-induced hepatitis in a mouse model. In vitro studies showed that curcumin reduced viral protein and titer levels and increased cell viability. Curcumin enhanced the heme oxygenase-1 (HO-1) protein level and decreased the levels of cleaved caspase-3 protein and mRNA of gene encoding C-X-C motif chemokine 10 in infected cells. In vivo studies showed that curcumin improved the survival rate and clinical scores in mice and reduced the viral titer in the liver during CVB3 infection. Moreover, the HO-1 levels were increased, and the cleaved caspase-3 levels were diminished in the CVB3-infected liver. Curcumin reduced the levels of interferon (IFN)-γ and monokine induced by IFN-γ in liver and levels of interleukin (IL)-8 in serum, but increased levels of regulated activation, normal T cell expression in liver and levels of IL-10 in serum of CVB3-infected mice. In summary, curcumin presents antiviral and anti-inflammation efficacies in CVB3 infection in vitro and in vivo; these results provide potential evidence on the feasibility of curcumin for clinical treatment.

Diagnostic dilemma in a patient with history of medullary thyroid carcinoma and abnormal serum liver enzymes; a case report with six years follow up

BackgroundMedullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from parafollicular C-cells. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are useful biomarkers for monitoring MTC cases.Case presentationHere, we describe a 48-year-old woman, who presented in 2014 with bilateral thyroid nodules. Report of fine needle aspiration was suspicious for MTC; initial laboratory evaluation showed serum Ctn level of 1567 pg/mL. After excluding type 2 multiple endocrine neoplasia syndrome clinically, total thyroidectomy and neck lymph node dissection were performed. The final histopathological diagnosis was right lobe MTC with neither vascular invasion nor lymph node involvement. On regular follow-up visits, Ctn and CEA levels have been undetectable, and repeated cervical ultrasonographic exams were unremarkable from 2014 to 2021. As liver enzymes became elevated in 2016, the patient was further evaluated by a gastroenterologist. Abdominopelvic ultrasonography revealed a coarse echo pattern of the liver parenchyma with normal bile ducts. A liver fibroscan showed a low fibrosis score (7kPa). The patient was recommended to use ursodeoxycholic acid. According to the progressive rise of liver enzymes with a cholestatic pattern in October 2020, a liver biopsy was performed that showed tiny nests of neuroendocrine-like cells with a background of primary biliary cholangitis (PBC). Immunohistochemical stainings were positive for chromogranin A (CgA), and synaptophysin and negative for Ctn, CEA, and thyroglobulin. Further imaging investigations did not reveal any site of a neuroendocrine tumor in the body. Considering normal physical exam, imaging findings, as well as normal serum levels of Ctn, CEA, CgA, and procalcitonin, the patient was managed as a PBC.ConclusionIn follow-up of a patient with MTC, we reported progressively increased liver enzymes with a cholestatic pattern. Liver biopsy revealed nests of neuroendocrine-like cells with a background of PBC, the findings that might suggest acquiring neuroendocrine phenotype by proliferating cholangiocytes.

Evaluating the bioequivalence of levetiracetam brand and generic oral tablets available in the Saudi market in vivo

BackgroundEpilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice. MethodsPharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice. ResultsPK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T1/2. In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks. ConclusionKeppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.

Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression.

Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown. Here, we aimed to test our working hypothesis that their combined incidence triggers CLD disease progression. We showed that patients with PiZZ/PNPLA3 I148M from the European alpha-1-antitrypsin deficiency (AATD) liver consortium and the UK Biobank had a trend towards higher liver enzymes, but no increased liver fat accumulation was evident between subgroups. After generating transgenic mice that overexpress the PiZ variant and simultaneously harbor the PNPLA3 I148M knockin (designated as PiZ/PNPLA3 I148M ), we observed that animals with PiZ and PiZ/PNPLA3 I148M showed increased liver enzymes compared to controls during aging. However, no significant difference between PiZ and PiZ/PNPLA3 I148M groups was observed, with no increased liver fat accumulation over time. To further study the impact on CLD progression, a Western-styled diet was administered, which resulted in increased fat accumulation and fibrosis in PiZ and PiZ/PNPLA3 I148M livers compared to controls, but the additional presence of PNPLA3 I148M had no impact on liver phenotype. Notably, the PiZ variant protected PNPLA3 I148M mice from liver damage and obesity after Western-styled diet feeding. Our results demonstrate that the PNPLA3 polymorphism in the absence of additional metabolic risk factors is insufficient to drive the development of advanced liver disease in severe AATD.

Biochemical Changes of Dexamethasone on Liver and Kidney Functions in Laboratory Mice Mus musculus L.

Background: The present study sought to verify the effect of dexamethasone on the biochemical changes in different organs, such as liver and kidney organs of both sexes, male and female mice. Materials &amp; Method: Muc muscular males and female mice (n=48) were used. To determine the effects of dexamethasone on the biochemical changes of liver and kidney organs, mice received a low dose (2mg/kg) and a high dose (4 mg/kg) of dexamethasone continuously for one month. Result: The results showed a significant increase (P&lt;0.05) in Liver enzymes (ALP, AST, ALT). The urea and creatinine levels also increased in the treated mice and both sexes with the pesticide compared with the control group. Keywords: mice, histological, liver, kidney, dexamethasone, toxicity

Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity in Rats: Biochemical and Histopathological Approaches in a Sub-chronic Study.

Chrysin (CH) is one of the important natural flavonoids with antioxidant and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos (CPF). We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated CH at 12.5, 25, and 50 mg/kg/day for 45 days. In this study, CPF increased liver enzyme activities compared with the control group (p < 0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p < 0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the concentrations of MDA and NO in the CPF group was observed compared with the control group (p < 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p < 0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in the serum concentration of IL-6 compared with the control animals. No significant changes were found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration of CH plus CPF induced histopathological alterations in liver. These results suggest that CH attenuates hepatic enzymes and histopathological alterations induced by CPF via modulating oxidative stress and inflammatory indices in rats.

Correlation of Neutrophil Lymphocyte Ration (NLR) Values with Severe Preeclampsia, HELLP Syndrome, and Eclampsia

Background: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. The disease is characterized by hypertension (≥140/90 mmHg), proteinuria, thrombocytopenia, renal failure, neurological complications, liver involvement, and fetal growth retardation. HELLP syndrome is a variant of preeclampsia that causes an increase in liver enzymes and a low platelet count. Eclampsia is the heaviest complication of preeclampsia. Neutrophil lymphocyte ratio (NLR) is part of the leukocyte type count examination which is an easy, available examination parameter and can be used as an index of the severity of systemic inflammation. This study aimed to determine the relationship of neutrophil-lymphocyte ratio (NLR) values with severe Preeclampsia, HELLP syndrome, and eclampsia.Method: This research is a comparative analytical study with a case control study approach. This research was conducted from April-November 2022. This study was conducted at the emergency room (ER) and inpatient department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Andalas – RSUP Dr. M. Djamil Padang. The study sample was part of the population that met the inclusion and exclusion criteria. The study required 108 samples, namely 27 from the severe preeclampsia group, 27 from the eclampsia group, 27 from the HELLP syndrome group, and 27 from the control group. Bivariate statistical analysis using Independent T-Test. Samples were taken by the method of consecutive sampling. The data were analyzed at a 95% confidence interval, if obtained p value&lt;0.05 then there is a significant relationship. The Data was analyzed by the SPSS computer program.Results: The results of this study obtained neutrophil-lymphocyte ratio in eclampsia has the highest average value compared with HELLP syndrome, severe preeclampsia, and control. While HELLP syndrome has a higher mean value than severe preeclampsia and control and subsequently severe preeclampsia also has a higher mean value NLR than control. This study found a significant relationship between neutrophil-lymphocyte ratio (NLR) with severe Preeclampsia, HELLP syndrome, and eclampsia (all p values=0.000).Conclusion: This study proves that neutrophil-lymphocyte ratio (NLR) has a significant relationship with severe Preeclampsia, HELLP syndrome, and eclampsia so further research can develop this study by analyzing other factors that affect preeclampsia. For clinicians can make this study as a reference in monitoring the progression of inflammation that occurs in severe preeclampsia, HELLP syndrome, and eclampsia.

Ameliorative effects of Orlistat and metformin either alone or in combination on liver functions, structure, immunoreactivity and antioxidant enzymes in experimentally induced obesity in male rats

BackgroundPrevalence of obesity is increasing worldwide. Obesity is associated with incidences of metabolic disorders and cardiovascular diseases and the risk of having it rose sharply during the COVID-19 pandemic. Obesity is associated with oxidative stress, inflammatory markers and hepatic disorders and has become one of the silent killer diseases affecting global health. MethodsThis study examined the effects of obesity on liver functions (ALT, AST and LDH), lipid profile (TG, TC, HDL-c, LDL-c and vLDL-c), tumour necrosis factor alpha (TNF-α), inflammatory marker, C-reactive protein (CRP), leptin hormone and antioxidant enzymes (CAT, SOD and GPx) and lipid peroxidation marker (MDA) in liver homogenates besides histological structure of the liver tissues and assessment of DNA damage. Fifty male Wistar rats were used and they were divided into five treatment groups: I-Control group, II-high-fat diet (HFD) treated group (Obesity) group, III-HFD plus Orlistat (ORL), IV-HFD plus metformin (Met) and V- HFD plus ORL plus Met. ResultsExperimentally-induced obesity caused a significant increase in liver enzymes including lipid markers (triglycerides and total cholesterol), inflammatory markers, tumour markers and lipid peroxidation markers and a concurrent decline in antioxidant enzymes and damage of liver main structures characterised by presence of congestion and accumulation of mononuclear inflammatory cells in blood sinusoids. In contrast, groups treated with either ORL or Met or both group, we recorded restoration of normal hepatic structures and a decline in DNA damage, liver enzymes and antioxidant levels. The best restoration and amelioration were observed in the group treated with a combination of ORL and Met. ConclusionOur findings indicated the synergistic effect of ORL and Met in ameliorating hepatic functions and lipid profile, alleviating inflammation, genotoxicity and side effects of experimentally-induced obesity.