Hepatic Biomarkers Research Articles

Impact of Streptococcus agalactiae Challenge on Immune Response, Antioxidant Status and Hepatorenal Indices of Nile Tilapia: The Palliative Role of Chitosan White Poplar Nanocapsule

A new insight into the synthesis of the herbal plant (White poplar, Poplus alba) leave extract using chitosan nanocapsule was studied. The in vitro antibacterial activity of chitosan white poplar nanocapsule (CWPNC) against Streptococcus agalactiae (S. agalactiae) was determined. About 120 fish were categorized for 7 days into four groups. The first and second (CWPNC) groups were treated with 0 mg/L and 3 mg/L CWPNC in the water, respectively, without being challenged; the first group was a control. The third (S. agalactiae) and fourth (CWPNC + S. agalactiae) groups were treated with 0 and 3 mg/L CWPNC, respectively, and challenged with S. agalactiae (0.5 × 107 CFU/mL). The obtained results revealed that CWPNC had an in vitro antibacterial activity against S. agalactiae. Moreover, S. agalactiae infection caused a significant elevation (p < 0.05) in the lipid peroxidation (malondialdehyde) and hepatorenal biomarkers, as well as the lowest significant (p < 0.05) survival rate (33.33%). Moreover, a significant depletion (p < 0.05) in the level of antioxidants (catalase and superoxide dismutase) and the immune indicators (immunoglobulin, lysozyme activity, and complement 3) were the consequences of S. agalactiae infection. Treatment of the infected fish with 3 mg/L CWPNC alleviated these bad circumstances.

Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production.

Short-term exposure to antimony induces hepatotoxicity and metabolic remodeling in rats

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution.

Antioxidant Potential and Improvement Activities of Sterculia setigera Delile on Insulin Resistance in Type 2 Diabetic Rats Induced by High-Fat Diet and Low Dose of Streptozotocin.

S. setigera is widely used in traditional medicine throughout the world. Ethnobotanical surveys have revealed its use to handle diabetes. This present research investigated the antioxidant potential and improvement activities of S. setigera Delile on insulin resistance in type 2 diabetic rats. Male rats fed high-fat diet for 6 weeks followed by a single-dose intraperitoneal injection of streptozotocin (35mg/kg) induced hyperglycemia. 72 hours after injection of streptozotocin, diabetic rats received treatment for 21days. Fasting blood glucose was measured. Serum biochemical and hepatic biomarkers were evaluated. A hepatic histological study was performed. Oxidative stress biomarkers were assessed in liver. Doses of 200 and 400mg/kg reduced the blood glucose with the reduction index of 53.75 and 62.1%, respectively. There was also good improvement in lipid profile and insulin. The dose of 400mg/kg better reduced subcutaneous fat mass with a difference in reduction index (1.5 to 5.8%). The extract resulted in a decrease in malondialdehyde levels and an increase in catalase activities. The extract showed significant inhibitory potential towards α-amylase 18.78% to 55.91% and α-glucosidase 23.91% to 67.76%. S. setigera extract could thus reverse insulin resistance and oxidative stress in type 2 diabetic rats induced.

Hepatoprotective Effect of Eulophia gracilis on Benzene-Induced Liver Toxicity in Wistar Rats

Benzene (BZ) is an organic solvent that can induce pathological disorders such as haematological disburbance and liver damage. Eulophia gracilis (EG) plant is a medicinal orchid explored traditionally to treat myriads of ailments including anemia and liver disease. The present study investigated the protective effect of Eulophia gracilis extract against Benzene-induced hepatotoxicity in haematologically disturbed rats. Male Wistar rats (110-120 g) were randomized into four groups (n = 6 / group): I (control), II BZ-treated: 175 mg/kgbw benzene every alternate days for two weeks; III Co-treated with 175 mg/kgbw benzene and E. gracilis 200 mg/kgbw each day for two weeks and IV administered 200 mg/kg of E. gracilis for two weeks. BZ caused a significant reduction in PCV, Hb, RBC and altered white blood cell count. Similarly, activities of hepatic biomarker enzymes such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase were significantly increased in the BZ-treated group relative to control. Furthermore, BZ caused a significant decrease in the activities of hepatic arylesterase, superoxide dismutase, catalase and glutathione-S-transferase and levels of Ascorbic Acid (AA) and Glutathione (GSH). A significant increase in hepatic malondialdehyde content, altered liver ultrastructure and modulation of p53 and BCl-2 protein in the liver also accompanied benzene intoxication. However, coadministration of E. gracilis ameliorated the BZ-induced changes in haematological parameter and liver biomarkers and improved hepatic antioxidant biomarkers and ultrastructure. Overall, the results suggest that Eulophia gracilis protected against BZ-induced hepatic oxidative damage and haematological disturbance in rats.

A STUDY OF CORRELATION BETWEEN GAMMA GLUTAMYL TRANSFERASE AND METABOLIC SYNDROME

CONTEXT:The metabolic syndrome ( Syndrome X, or insulin resistance syndrome) is a combination of several risk factors that contribute to atherosclerotic cardiovascular disease (ASCVD). Elevated blood pressure, triglycerides, hyperglycemia, waist circumference and low HDL- cholesterol are all symptoms of accelerated dyslipidemic atherogenesis. Glutamyl transferase (GGT) has long been thought to be a biomarker for hepatic and biliary illness and alcoholic related disease. GGT is required for the extracellular catabolism of glutathione, which is the most important thiol antioxidant in humans.It co localizes with oxidised low density lipoprotein (LDL) and foam cells in the atheromatous core of coronary plaques. GGT can be a proinammatory sign. GGT was found to be a prognostic marker for Metabolic syndrome, CVD, and heart failure .AIM: Study of Gamma glutamyltransferase in metabolic syndrome patients. MATERIALS AD METHODS: A sample size of 100 patients admitted in medicine and other departments in nri general hospital are included in study Qualitative data was expressed in frequencies and percentages a STASTISTICAL ANALYSIS: nd Quantitative data in mean and standard deviation. Non parametric statistics i.e. Chisquare test was used to nd the signicant association between the two qualitative variables. Independent t test and ANOVA were used to nd the statistical signicance between quantitative variables. Pearson correlation coefcient was used to nd correlation between two variables. p value of <0.05was considered statistically signicant. CONCLUSION: It should be highlighted that elevated levels of GGT are not the only hepatic biomarker of hepatic steatosis, as evidenced by ndings from several research. lines of evidence point to a link between high GGT levels in the blood and the metabolic syndrome. As a result, higher GGT levels are associated with increased insulin resistance and a higher risk of type 2 diabetes .

Protective Effect of Herbal Medicinal Plant Extract against Carbon Tetrachloride Induced Liver Injury in Rat

Adiantum capillus (AC) Linn (Family: Adiantaceae) commonly known as “Hansraj” It is used in common cold, cough, pyrexia inflammation, acts as purgative. It improves digestion and renal function. This study was performed to investigate the hepato-defensive potential of Adiantum capillus in contradiction of carbon tetrachloride tempted hepatic damage in rats. The rodents were dosed with Acetonic extract (AEAC, 500mg/kg) extract of Adiantum capillus against Carbon Tetrachloride induced hepatic damage. Results shows thst Carbon Tetrachloride elevated the level of hepatic markers like SOPT, SGPT, bilirubin and ALP as well as altered the antioxidant enzymes. The level of hepatic biomarkers, as well as antioxidant enzyme, were recovered after the administration of at 500mg/kg, p.o., which was further confirmed by the histopathological. From above results it was concluded that The Acetonic extract (500 mg/kg, bw) extract of Adiantum capillus (ACE) recover the biochemical as well as antioxidant parameters, which were affected by Carbon Tetrachloride. The histopathological analysis supports the outcomes of antioxidants parameters.
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Assessment of zootechnical parameters, intestinal digestive enzymes, haemato-immune responses, and hepatic antioxidant status of Pangasianodon hypophthalmus fingerlings reared under different stocking densities

A 3-month experiment was designed to investigate the effects of different stocking densities on growth, stress markers, intestinal digestive enzymes, hepatic antioxidant biomarkers, serum immunity, and survivability of striped catfish, Pangasianodon hypophthalmus. The relationship between fish stocking densities and water quality parameters was also assessed. Healthy fish (n = 1260 individuals, 17.52 ± 0.20 g) were raised in twelve fiberglass tanks. Triplicate fish groups with stocking densities of 60, 90, 120, or 150 fish per 1 m3 were designed, further referred to as SD60, SD90, SD120, and SD150 groups. Fish feeding was done using a commercially purchased well-balanced diet three times per day with a feeding rate of 3% of the wet fish weight. Results revealed that un-ionized ammonia, nitrite, and pH were significantly elevated, and dissolved oxygen levels were decreased significantly with increasing the stocking densities. The survival rates and growth significantly decreased with increasing fish stocking densities. The intestinal lipase, protease, trypsin, and amylase enzymes decreased significantly (P < 0.05) along with increased stocking densities. Moreover, significant decreases were noticed in total protein, lysozyme activity, and globulin levels when the stocking density was higher than 60 fish/m3. Conversely, serum stress biomarkers (such as blood glucose and cortisol), transaminases, alkaline phosphatase, and blood urea nitrogen were significantly elevated with increasing stocking densities. Hepatic CAT, SOD, and T-AOC were decreased; meanwhile, hepatic MDA levels were significantly increased, together with the stocking rates. In the end, we found that the SD150 group recorded the lowest growth rates, immune responses, and antioxidant capacity and the highest stress markers as blood glucose and cortisol. In this context, we can conclude that the stocking 60 fish/m3 resulted in better growth, survival, immunity, antioxidant status, and overall performances of striped catfish.Graphical

Hepatic Coccidiosis in Wild Rabbits in Greece: Parasite Detection on Liver Imprints and the Associated Biochemical Profile.

(1) Background: Rabbit hepatic coccidiosis, caused by Eimeria stiedae, is a devastating disease with high morbidity and mortality rates. The disease is well described in rabbits, but little is known about E. stiedae infection in wild rabbits. In this study, we investigated the presence of E. stiedae infection in wild rabbits from the island of Lemnos, Greece, where this species is overpopulated, and the effects of infection on common hepatic biomarkers. (2) Methods: We used liver impression smears to detect the coccidian oocysts, and we defined the liver biochemical profile of the infected individuals. (3) Results: Overall, 13.3% of the liver imprints examined were positive for the presence of coccidial oocysts. The activities of liver enzymes, that is, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamyltransferase (GGT), as well as globulins (GLOB), were increased while the concentrations of albumins (ALB), total proteins (TP) and the albumin to globulin (A/G) ratio were decreased in the infected individuals compared to the non-infected ones. (4) Conclusions: This study adds to the current knowledge on the pathogens affecting wild rabbits and those circulating in this population on the island of Lemnos, Greece. Moreover, we showed that E. stiedae infection exerts pathological effects on the hepatocyte integrity and liver function of wild rabbits, as reflected by the abnormal values of liver injury and dysfunction biomarkers.

Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

The influence of ecological factors in the modulation of pollution biomarkers of two small pelagic marine fish

Biomarkers are useful tools for the detection of marine pollution, which is poorly monitored in the pelagic environment. In this study, we investigated the role of key biological and environmental factors on three hepatic xenobiotic biomarkers: carboxylesterases (CEs), glutathione S-transferase (GST) and catalase (CAT). Additionally, ethoxyresorufin-O-deethylase (EROD) and benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) activities were determined for comparative purposes. The pelagic species targeted were the European anchovy (Engraulis encrasicolus) and the European sardine (Sardina pilchardus). The results revealed sex-dependent CE activities in sardine. CEs and GST activities were significantly affected by reproduction and, in anchovy, CE activities were also influenced by temperature. In vitro incubations revealed that the pesticide dichlorvos caused up to 90 % inhibition of basal CEs activity. This work highlights that the reproductive status, temperature and sex, modulate biomarker responses, and that anchovy would be more suitable pelagic bioindicator due to its higher in vitro sensitivity to dichlorvos and sex-independent biomarker responses.

Galectin-3 is a key hepatoprotective molecule against the deleterious effect of cisplatin

AimsEvaluate the role of galectin-3 in the liver using an acute model of cisplatin-induced toxicity. Material and methodsModified citrus pectin (MCP) treatment was used to inhibit galectin-3. Rats were distributed into four groups: SHAM, CIS, MCP and MCP + CIS. On days 1–7, animals were treated by oral gavage with 100 mg/kg/day of MCP (MCP and MCP + CIS groups). On days 8, 9 and 10, animals received intraperitoneal injection of 10 mg/kg/day of cisplatin (CIS and MCP + CIS groups) or saline (SHAM and MCP groups). Key findingsCisplatin administration caused a marked increase in hepatic leukocyte influx and liver degeneration, and promoted reactive oxygen species production and STAT3 activation in hepatocytes. Plasma levels of cytokines (IL-6, IL-10), and hepatic toxicity biomarkers (hepatic arginase 1, α-glutathione S-transferase, sorbitol dehydrogenase) were also elevated. Decreased galectin-3 levels in the livers of animals in the MCP + CIS group were also associated with increased hepatic levels of malondialdehyde and mitochondrial respiratory complex I. Animals in the MCP + CIS group also exhibited increased plasma levels of IL-1β, TNF-α, and aspartate transaminase 1. Furthermore, MCP therapy efficiently antagonized hepatic galectin-9 in liver, but not galectin-1, the latter of which was increased. SignificanceReduction of the endogenous levels of galectin-3 in hepatocytes favors the process of cell death and increases oxidative stress in the acute model of cisplatin-induced toxicity.

Assessment of liver fibrosis using a 3-dimensional high-resolution late gadolinium enhancement sequence in children and adolescents with Fontan circulation.

To assess abnormal liver enhancement on 15-20min delayed 3D high-resolution late gadolinium enhancement (3D HR LGE) sequence in patients with Fontan circulation. Retrospective study of pediatric Fontan patients (< 18years old) with combined cardiac-liver MRI from January 2018 to August 2021. Abnormal hepatic enhancement was graded (0-3) for each lobe, summed for a total liver enhancement score (0-6), and compared to repaired tetralogy of Fallot (rTOF) patients. Correlations with other hepatic imaging biomarkers were performed. Temporal relationships of enhancement compared to traditional early portal venous and 5-7-min delayed phase liver imaging were analyzed. The Fontan group (n = 35, 13 ± 3.4years old, median time from Fontan 10 (9-12) years) had 23/35 (66%) with delayed 3D HR LGE total liver enhancement score > 0 (range 0-5), with greater involvement of the right lobe (1 (0-1) vs 0 (0-1), p < 0.01). The rTOF group (n = 35, 14 ± 2.6years old) had no abnormal enhancement. In the Fontan group, total liver enhancement was 3 (2-4) in the early portal venous phase, lower at 1 (1-2) in the 5-7-min delayed phase (p < 0.01), and lowest at 1 (0-2) in the 15-20-min delayed phase (p = 0.03). 3D HR LGE enhancement correlated inversely with portal vein flow (rs = - 0.42, p = 0.01) and positively with left lobe stiffness (rs = 0.51, p < 0.01). The enhancement score decreased in 13/35 (37%) between the 5-7- and 15-20-min delayed phases. Liver fibrosis can be assessed on 3D HR LGE sequences in patients with Fontan circulation, correlates with other imaging biomarkers of Fontan liver disease, and may add information for hepatic surveillance in this population. • Abnormal liver enhancement on 3D HR LGE sequences in Fontan patients likely represents liver fibrosis and is seen in up to 66% of children and adolescents with variable distribution and severity. • The degree of 3D HR LGE liver enhancement correlates with decreased portal vein flow and increased left hepatic lobe stiffness.

Polysaccharides from Tumorous stem mustard prevented high fructose diet-induced non-alcoholic fatty liver disease by regulating gut microbiota, hepatic lipid metabolism, and the AKT/FOXO1/MAPK signaling pathway

Ingestion of 30 % fructose water (HF) for eight weeks caused non-alcoholic fatty liver disease (NAFLD) in mice and manifested in prominent weight gain, insulin resistance, abnormal lipid metabolism, oxidative stress, and liver damage. Biochemical analysis suggested that treatment with non-starch polysaccharides extracted from Tumorous stem mustard (NSPTSM) at 25–50 mg/kg·bw prevents these symptoms in HF-induced NAFLD. 16S rRNA sequencing revealed that NSPTSM balanced the HF-perturbed colonic microbiota and significantly increased the relative abundance of Akkermansia in mice. Metabonomics results indicated that the hepatic biomarkers were LPE (18:1/0:0) and LPC (16:1/0:0), which were negatively related to cecal 23-nordeoxycholic acid. Transcriptome and western blot analysis suggested that protein kinase B (AKT)/forkhead box protein O-1 (FOXO1)/mitogen-activated protein kinase (MAPK) signaling pathway played an important role in prevention of HF-induced NAFLD by NSPTSM. These findings indicated that NSPTSM protected mice against HF-induced NAFLD and underscored the efficacy of utilizing NSPTSM as a possible prebiotic.

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats.

Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200mg/kg, i. p.) with resveratrol (20mg/kg, oral gavage). All groups received their dose once daily for 7days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.

Association of plasma metabolites and diagnostic imaging findings with hepatic lipidosis in bearded dragons (Pogona vitticeps) and effects of gemfibrozil therapy.

To evaluate the association between plasma metabolites, biochemical analytes, diagnostic imaging findings, and the histologic diagnosis of hepatic lipidosis in bearded dragons. To assess the effects of gemfibrozil therapy on hepatic lipid accumulation and associated diagnostic tests. Fourteen bearded dragons (Pogona vitticeps) with varying severity of hepatic lipid accumulation (with and without hepatic lipidosis) were included. Animals underwent coelomic ultrasound, computed tomography (CT) scans, and coelioscopic hepatic biopsies. Clinical pathology tests included lipidologic tests, hepatic biomarkers, and mass spectrometry-based metabolomics. Animals were medicated with gemfibrozil 6mg/kg orally once a day for 2 months in a randomized blinded clinical trial prior to repeating previous diagnostic testing. Hounsfield units on CT were negatively associated with increased hepatic vacuolation, while ultrasound and gross evaluation of the liver were not reliable. Beta-hydroxybutyric-acid (BHBA) concentrations were significantly associated with hepatic lipidosis. Metabolomics and lipidomics data found BHBA and succinic acid to be potential biomarkers for diagnosing hepatic lipidosis in bearded dragons. Succinic acid concentrations were significantly lower in the gemfibrozil treatment group. There was a tendency for improvement in the biomarkers and reduced hepatic fat in bearded dragons with hepatic lipidosis when treated with gemfibrozil, though the improvement was not statistically significant. These findings provide information on the antemortem assessment of hepatic lipidosis in bearded dragons and paves the way for further research in diagnosis and treatment of this disease.

Effect of gambogenic acid in attenuating diethylnitrosamine (DEN)-induced hepatocellular carcinoma in rat model

Liver cancer, specifically hepatocellular carcinoma has been a widespread problem among general population. This study aims to investigate the modulating mechanism of gambogenic acid, a phenolic xanthonoid, in diethylnitrosamine (DEN)-induced liver cancer in rats. Male Wistar albino rats were clustered into four groups (n = 6). Group I served as control treated with normal saline. Hepatocellular carcinogenesis was induced in rats by single intraperitoneal (i.p.) administration of DEN in saline (200 mg/kg b.w.) for groups II and III. Group III received oral administration of gambogenic acid (20 mg/kg b.w.) one hour post DEN administration, whereas group IV received oral administration of gambogenic acid (20 mg/kg b.w.) alone. Rats were sacrificed after 16 weeks to determine the levels of hepatic biomarkers, oxidative stress markers, hematological profile and histopathological changes. Gambogenic acid significantly ameliorated the expressions of oxidative stress markers TBARS, GSH (P < 0.05), enzymatic antioxidants GPx, CAT, SOD, GST (P < 0.05), apoptosis mediators (P < 0.05), and serum biomarkers for liver damage and tumor formation (P < 0.05) compared with DEN-induced model group. Hepatocellular levels of 8-OHdG were significantly diminished (P < 0.05) by gambogenic acid against the damage incurred by DEN. Liver histopathological derangements caused by DEN were reversed by gambogenic acid. The results clearly impacted the effect of gambogenic acid in attenuating DEN-induced hepatocellular carcinoma in rats mediated through NF-kβ pathway and hepatocellular oxidative damage.

Antioxidant Effects of Nigella sativa and Its Modulating Role on Hepatotoxicity Induced by Dietary Frying Oil in Rats

Repeated use of frying oil threatens — more than ever — human beings and this is due to the increased consumption of fried and fast foods. This study aimed to investigate the antioxidant effects of Nigella sativa against fryingoil-induced hepatic and oxidative alterations. In total, 40 male rats were divided into four groups and were treated during 30 consecutive days with frying oil and/or nigella. (EO-0) group: Rats were served as control and received a normal diet. (EO-N) group: Rats were fed with an experimental diet containing 2% nigella. (FO-0) group: Rats were nourished on diet containing 7% frying oil. (FO-N) group: Rats were received a combination diet containing 7% frying oil and 2% nigella. The physicochemical analyses indicate that frying oil contains very high concentrations of toxic substances compared to edible oil. The consumption of frying oil causes a significant increase in hepatic biomarkers and intensifies in oxidative stress status compared to the control group. Moreover, the hepatic histological sections of rats fed with frying oil showed a disrupted architecture. The combination of nigella with frying oils in rats’ diet revealed an intense reduction in the oxidative stress and ameliorated the levels of the majority of the previous parameters. Nigella supplementation confirmed their potential antioxidant activities. Therefore, administration of nigella seems to be the excellent spice recommended in high-temperature food frying in order to maintain human health.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Evaluation of drug carrier hepatotoxicity using primary cell culture models

This study aims to establish a primary rat hepatocyte culture model to evaluate dose-dependent hepatotoxic effects of drug carriers (lipopolymer nanoparticles; LPNs) temporal. Primary rat hepatocyte cell cultures were used to determine half-maximal Inhibition Concentrations (IC50) of the drug-carrier library. Drug-carrier library, at concentrations <50 μg/mL, is benign to primary rat hepatocytes as determined using albumin and urea secretions. Albumin, as a hepatic biomarker, exhibited a more sensitive and faster outcome, compared to urea, for the determination of the IC50 value of LPNs. Temporal measurements of hepatic biomarkers including urea and albumin, and rigorous physicochemical (hydrodynamic diameter, surface charge, etc.) characterization, should be combined to evaluate the hepatotoxicity of drug carrier libraries in screens.