Histopathological Changes In Liver Research Articles

Spiramycin-chitosan Nanoparticles Decline Parasite Burden and Renovate Patent Histopathological Changes in Liver and Lung in Mice Experimentally Infected with Acute Toxoplasmosis

Spiramycin-chitosan Nanoparticles Decline Parasite Burden and Renovate Patent Histopathological Changes in Liver and Lung in Mice Experimentally Infected with Acute Toxoplasmosis

Evaluation of the hepatotoxicity of buprenorphine in rat pups born to an exposed mother during lactation.

BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation. The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP. In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

Green synthesis, characterization, and hepatoprotective effect of zinc oxide nanoparticles from Moringa oleifera leaves in CCl4-treated albino rats

Hepatotoxin carbon tetrachloride (CCl4) causes liver injury. This research aims to create ZnO-NPs using green synthesis from Moringa oleifera (MO) leaves aqueous extract, and chemically prepared and confirming the synthesis by specialized equipment analysis. The sizes formed of ZnO-NPs were 80 and 55 nm for chemical and green methods, respectively. In addition, to study their ability to protect Wistar Albino male rats against oxidative stress exposed to carbon tetrachloride. MO leaf aqueous extract, green synthesized ZnO-NPs, and ZnO-NPs prepared chemically at 100 and 200 mg/kg BW per day were investigated for their hepatoprotective effects on liver enzyme biomarkers, renal biomarkers, antioxidant enzymes, lipid peroxidation, hematological parameters, and histopathological changes. Compared to the control group, all liver and kidney indicators were considerably elevated after the CCl4 injection. However, the activity of antioxidant enzymes in the liver was significantly reduced after the CCl4 injection. These outcomes indicate that MO leaf aqueous extract, greenly synthesized ZnO-NPs, and ZnO-NPs chemically prepared can restore normal liver and kidney function and activity, as well as hematological and antioxidant enzymes. The highest impact on enhancing the hepatoprotective effect was recorded for rats that received green synthesized ZnO-NPs. The increased drug delivery mechanism of green synthesized ZnO-NPs resulted in a higher protective effect than that of MO leaf aqueous extract.

The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: An analysis of the data from Toxicity Reference Database (ToxRefDB).

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

Clinicopathological features of Sjogren's syndrome complicated with liver injury

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Inverse relationship between HBV DNA levels and liver histopathological changes in immune-tolerant CHB patients.

Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.

Acute toxicity and anti-enterotoxigenic activity of pigment extracted from Micrococcus roseus.

Microbial pigments are considered as one of the main sources of natural types, and the attention to them is increasing in the food and pharmaceutical industries. This study aimed to investigate the effects of pigments extracted from Micrococcus roseus (PEM) on the gene expression of a and b staphylococcal enterotoxins (sea and seb) and their acute toxicity. Real-time PCR was used to study the anti-enterotoxigenic activity of PEM against Staphylococcus aureus at sub-inhibitory concentrations. In addition, the acute toxicity of PEM was evaluated on albino mice through alkaline phosphatase (ALP), aspartate aminotransferas (AST), and alanine aminotransferase (ALT) of liver and its histopathological changes. Based on the results, the expression of sea and seb was decreased in the presence of PEM at sub-inhibitory concentrations. The 2-∆∆CT was measured 0.02 and 0.01 for the expression of sea and seb of S. aureus grown in the MHB containing 16mg/ml PEM. The results showed that the expression of seb is more sensitive to PEM compared to the expression of sea. After treatment of mice with PEM for two weeks, the condition of mice was normal, and the results of liver enzymatic activities and histopathological changes showed insignificant difference compared to the control sample.

Toxicological assessment of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid herbicide in combination on Cirrhinus mrigala using multiple biomarker approach

The widespread application of herbicides raises concerns about their impact on non-target aquatic organisms. This study aimed to evaluate the toxicity of a commercially available herbicide formulation containing Bromoxynil+MCPA (2-Methyl-4-chlorophenoxyacetic acid) on Cirrhinus mrigala (economically significant fish). A total of 210 juvenile fish were subjected to a triplicate experimental setup, with 70 fish allocated to each replicate, exposed to seven different concentrations of herbicide: 0 mg/L, 0.133 mg/L, 0.266 mg/L, 0.4 mg/L, 0.5 mg/L, 0.66 mg/L, and 0.8 mg/L, respectively, for a duration of 96 h. The median lethal concentration (LC50) was determined to be 0.4 mg/L. Significant hematological alterations were observed, including decreases in RBC counts, hemoglobin, hematocrit, and lymphocyte counts, along with an increase in erythrocyte indices. Biochemical analysis revealed elevated levels of neutrophils, WBCs, bilirubin, urea, creatinine, ALT, AST, ALP, and glucose in treated groups. Morphological abnormalities in erythrocytes and histopathological changes in gills, liver, and kidneys were noted. Pathological alterations in gills, liver and kidneys including epithelial cell uplifting, lamellar fusion, hepatolysis, and renal tubule degeneration were observed. Oxidative stress biomarkers such as TBARS (Thiobarbituric Acid Reactive Substance), ROS (Reactive Oxygen Species), and POD (Peroxides) activity increased, while antioxidant enzymatic activities decreased as toxicant doses increased from low to high concentrations. The study reveals that Bromoxynil+MCPA significantly disrupts physiological and hematobiochemical parameters in Cirrhinus mrigala, which highlights the substantial aquatic risks. In conclusion, the herbicide formulation induced significant alterations in various fish biomarkers, emphasizing their pivotal role in assessing the environmental impact of toxicity. This multi-biomarker approach offers valuable insights regarding the toxicological effects, thereby contributing substantially to the comprehensive evaluation of environmental hazards.

Immunomodulatory potential of Sarcophaga argyostoma larval hemolymph as a natural alternative to berenil in treating Trypanosoma evansi in vivo

This study compared effects of diminazene aceturate (berenil), commonly used to treat domestic animals infected with Trypanosoma evansi, with the hemolymph of Sarcophaga argyostoma larva. The hemolymph may be acting as a possible natural alternative to berenil, based on immunomodulation mediated inflammatory response. Inflammatory mediators and histopathological changes in liver, kidney, and spleen of albino mice experimentally infected with T. evansi were studied. Mice were divided into five groups: G1, uninfected, untreated (negative control); G2, T. evansi infected (positive control); G3, infected and treated with berenil; G4, infected and treated with hemolymph; G5, infected and treated with hemolymph 3 days before infection (prophylactic group). Animals in (G4) and (G5) exhibited a significant overall reduction in serum levels of IFN-γ. However, the reduction in TNF-α and IL-6 levels was more limited compared to (G2) and (G3). Notably, an elevation in IL-10 levels was observed compared to animals in other groups. Furthermore, the groups treated with hemolymph demonstrated an alleviation of T. evansi infection in contrast to the other groups. This study highlights that the administration of Sarcophaga argyostoma larval hemolymph at a dosage of 0.5 ml/kg significantly inhibited T. evansi organisms in vivo, showcasing a pronounced trypanocidal effect.

Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk.

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

Potential therapeutic effect of Thymoquinone on Cisplatin-induced hepatotoxicity in rats

Aim: Cisplatin (CIS), an antineoplastic agent, shows serious side effects such as hepatotoxicity. Thymoquinone (ThQ) is a powerful anti-oxidant with many beneficial effects such as anti-inflammatory, anti-tumoral. The aim of this study was to investigate whether ThQ treatment has hepatoprotective effect in CIS-induced hepatotoxicity model in rats and also to determine how CIS and/or ThQ treatments affect OTULIN levels, one of the deubiquitinases, in liver tissue. Materials and Methods: The 28 rats used in the study control (application not done), CIS (7 mg/kg CIS, first day of experiment, intraperitoneal), CIS+ThQ (7 mg/kg CIS, first day of experiment, intraperitoneal + 10 mg/kg/day ThQ, oral gavage) and ThQ (10 mg/kg/day ThQ, oral gavage) were divided into four equal groups (n=7). The experiment was terminated upon completion of all applications (day 15). The effects of CIS and\or ThQ apps on liver tissues were examined biochemically, histopathologically and immunohistochemically. Results: CIS application increased liver enzyme levels, histopathological changes, inflammation, oxidative stress and apoptosis in liver tissue and caused a decrease in OTULIN level. However, ThQ administration showed a positive regulatory effect on CIS-induced changes in liver tissue. Conclusion: ThQ supplementation has a hepatoprotective effect against CIS-induced liver tissue damage.

Gallstone-Associated Histopathological Changes in Liver: A Prospective Observational Study.

To assess the effect of gallstone disease on liver parenchyma and the prevalence and extent of liver pathology in cholelithiasis in our population at the Department of General Surgery, Indira Gandhi Institute of Medical Science (IGIMS), Patna. The present prospective observational study was conducted on 100 either-sex patients scheduled for open or laparoscopic cholecystectomy. In all the patients, laboratory and radiological investigations were performed. An undamaged portion of the liver edge around the gallbladder fossa was selected and held by atraumatic forceps. Using sharp scissors, around 1 cm of the liver edge was taken out and sent for histopathological examination. The mean age of the patients was 39.28 ± 13.73 years. The majority of patients were females (69%). Pain was the predominant clinical feature in 51% of the patients, followed by vomiting (21%), nausea (18%), and indigestion (10%). In 36% of cases, the liver histology was abnormal, including steatosis, fibrosis, cholestasis, portal tract infiltration, and lobular parenchymal infiltration. A significant association was found between the duration of symptoms and abnormal histology findings (P<0.0001). Gallstone disease is associated with notable alterations in liver histology, and these changes tend to be more prevalent in individuals with a prolonged duration of symptoms.

Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl4-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl4. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

Effect on Endoplasmic Reticulum Stress of the Combined Oral Contraceptives in the Kidney

Objective: This study aimed to analyze the effects of combined oral contraceptive active ingredients, Drospirenone, Ethinyl Estradiol, and Ethinyl Estradiol+Drospirenone, on liver histopathological changes and endoplasmic reticulum stress levels. Material and Methods: In the study, 37 Balb/c female mice were used. Mice were randomly divided into the Control, Sham, Drospirenone, Ethinyl Estradiol, and Ethinyl Estradiol+Drospirenone groups. The experimental groups were administered with gavage to 8-week-old female mice for 35 days. Kidney tissue sections were applied with Hematoxylin&amp;Eosin, Orcein, Mallory’s Azan, and Periodic Acid-Schiff to detect histopathological changes, and Chop and Grp78 were used to detect Endoplasm Reticulum Stress. Results: Significant loss of microvilli and a decrease in glycogen accumulation were observed in the apical part of some of the proximal tubules of animals in the Drospirenone and Ethinyl Estradiol+Drospirenone groups. The amount of collagen fiber stained with Mallory’s Azan increased in the parietal layer of Bowman’s capsule of the kidney tissues of the Drospirenone and Ethinyl Estradiol+Drospirenone applied groups, but no difference was observed in elastic fibers in all groups. The expression level of Grp78 and Chop proteins in the kidney tubules of female mice given Drospirenone, Ethinyl Estradiol, and Ethinyl Estradiol+Drospirenone was significantly higher compared to the control group. Conclusion: In this study, it was shown that the expression of Grp78 and Chop markers detected in the mouse kidney increased as a result of Drospirenone, Ethinyl Estradiol and Ethinyl Estradiol + Drospirenone administration, thus causing kidney cell apoptosis by inducing ER-dependent death pathway activity.

The Hepato and Reno Protective Role of Curcumin against the Alterations in Some Biochemical Parameter and Histological Damage Induced by Monosodium Glutamate in Male Albino Rats

The main objective of current research was to investigate toxicity effect of Monosodium glutamate and protective role of Curcumin on some blood biochemical parameters, body weight gain, relative organ weight and histopathological alterations in liver and kidney tissues in male albino rats. Twenty animals of male rats (Rattus norvegicus), their weight ranged from 111 to 165 gm. The animals were divided into four groups: Each animal group contained five rat, first group was control negative (-ve) administrated distilled water, the second group was control positive (+ve) administrated curcumin, third group was administrated by Monosodium glutamate (MSG) at dose 20 mg per one Kg and the forth group was administrated by Monosodium glutamate (MSG) at dose 20mg/Kg of body weight + curcumin at dose 100 mg per one Kg of body weight. All animal groups were administrated orally about 30 days. The study recorded significant p≥0.05 increment in liver and kidney function parameters included [Alanine transaminase (ALT), Aspartate aminotransferase (AST), Urea and creatinine] after oral administration of animals with MSG and MSG + Curcumin as a comparison with control groups. The study recorded significant decrement p≥0.05 in liver and kidney function parameters included ALT, AST, Urea and creatinine) in group was administrated MSG + Curcumin in comparison with group was administrated MSG only. Additionally, current study revealed histopathological changes in liver and kidney tissue in groups were administrated MSG and MSG+ curcumin compared with + curcumin compared with control groups. Furthermore, the study revealed that curcumin had protective effect and result in slight histopathological changes in liver and kidney tissue by reducing the damage and in group was treated by MSG+ curcumin for 30 days compared with MSG treated group.

Sanghuangporus vaninii extract ameliorates hyperlipidemia in rats by mechanisms identified with transcriptome analysis.

The increasing incidence of hyperlipidemia is a serious threat to public health. The development of effective and safe lipid-lowering drugs with few side effects is necessary. The purpose of this study was to assess the lipid-lowering activity of Sanghuangporus vaninii extract (SVE) in rat experiments and reveal the molecular mechanism by transcriptome analysis. Hyperlipidemia was induced in the animals using a high-fat diet for 4 weeks. At the end of the 4th week, hyperlipidemic rats were assigned into two control groups (model and positive simvastatin control) and three treatment groups that received SVE at 200, 400, or 800 mg kg-1 day-1 for another 4 weeks. A last control group comprised normal chow-fed rats. At the end of the 8th week, rats were sacrificed and lipid serum levels, histopathology, and liver transcriptome profiles were determined. SVE was demonstrated to relieve the lipid disorder and improve histopathological liver changes in a dose-dependent manner. The transcriptomic analysis identified changes in hepatocyte gene activity for major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone signaling, and glucagon signaling. The changed expression of crucial genes in the different groups was confirmed by qPCR. Collectively, this study revealed that SVE could relieve hyperlipidemia in rats, the molecular mechanism might be to promote the metabolism of lipids and the excretion of cholesterol, inhibit the biosynthesis of cholesterol by activating the AMPK signaling pathway, the thyroid hormone signaling pathway, and the glucagon signaling pathway.

Ameliorating Potential of Curcumin and Ascorbic Acid Against Hepatotoxicity Caused by Synergistic Effect of Heavy Metals in Male Albino Rats

The ameliorative role of combination of curcumin and ascorbic acid (low and high doses) was determined against biochemical and histopathological changes in liver caused due to synergistic effects of heavy metals (As, Cd and Pb) present above permissible limits in drinking water for 60 and 90 days in 84 male albino rats. The histology of liver in rats treated with a mixture of low as well as high doses of heavy metals showed mild alternations after 60 days and intense damage after 90 days. The content of biochemical parameters like proteins and lipids were significantly decreased and cholesterol, phospholipids and fatty acids were significantly increased after 60 and 90 days of treatment. The rats treated with curcumin and ascorbic acid showed restoration of histological damage and content of biochemical components indicated amelioration of hepatotoxicity effectively up to 60/90 days depending upon the dose of heavy metals, curcumin and ascorbic acid.

Investigating the Protective Effect of Ellagic Acid on Cholemic Nephropathy in Cholestatic Rats

Background: Cholemic nephropathy (CN), a renal dysfunction caused by bile acids, is a severe complication of chronic liver damage and bile duct ligation (BDL), which may lead to complete kidney failure. Objectives: This study investigated the protective effect of ellagic acid on CN in cholestatic rats. Methods: Sixty male Wistar rats weighing about 180 - 200 g were randomly divided into 6 groups for in vivo investigation. The rats were randomly divided into 5 groups of 10. Cholestasis was induced in rats by closing the bile ducts; then, the animals were treated with different doses of ellagic acid (10, 25, and 50 mg/kg). Then, the induction effect of cholestasis and the protective effects of ellagic acid on serum and urinary factors, oxidative stress indices, and histopathological changes in liver and kidney tissue were investigated. Results: Bile duct ligation in rats led to an increase in serum and urinary factors. It was also associated with increased reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) oxide form, decrease in antioxidant systems, GSH and severe histopathological changes, and fibrosis of the liver and kidney tissues. Another finding of this research was the beneficial effect of ellagic acid in improving serum and urinary factors, oxidative stress indices, and histopathological changes. Conclusions: Due to its antioxidant properties, ellagic acid can potentially serve as a novel therapeutic approach for treating kidney damage caused by increased serum levels of bile acids.

Evaluation of the protective effect of losartan in acetaminophen-induced liver and kidney damage in mice

Acetaminophen is widely used among humans as an antipyretic and analgesic. In this study, the protective effect of losartan in hepatotoxicity and nephrotoxicity induced by acetaminophen in mice was investigated owing to its anti-inflammatory and antioxidant effects. An injection of a single dose of 500 mg/kg (i.p.) acetaminophen was administered to induce hepatotoxicity and nephrotoxicity in Groups VI–X. Losartan at doses of 1 mg/kg (Group VII), 3 mg/kg (Group VIII), and 10 mg/kg (Groups III, V, IX, and X) was injected intraperitoneally twice, at 1 and 12 h after the acetaminophen injection. Additionally, a 4 mg/kg dose of GW9662 (peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist) was injected intraperitoneally 30 min before the losartan injections in Groups V and X. At the end of 24 h, the mice were euthanized, and blood, liver, and kidney tissue samples were collected. Levels of AST, ALT, creatinine, and oxidative stress markers including TBARS, SOD, CAT, GPx, TAS, TOS, GSH, and GSSG, along with pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-10, IL-17, and TNF-α, were measured using ELISA kits. Additionally, a histological evaluation of the tissue samples was performed. Acetaminophen causes increases in the levels of AST, ALT, creatinine, TBARS, TOS, GSSG, IL-1β, IL-6, IL-8, IL-10, IL-17, and TNF-α in serum, liver, and kidney tissue. Meanwhile, it led to a decrease in the levels of SOD, CAT, GPx, TAS, and GSH. Losartan injection reversed oxidative and inflammatory damage induced by acetaminophen. Histopathological changes in liver and kidney tissue were alleviated by losartan. The substance GW9662 increased the protective effect of losartan. In light of all the data obtained from our study, it can be said that losartan has a protective effect on liver and kidney damage induced by acetaminophen due to its antioxidant and anti-inflammatory effects. In terms of the study, losartan was found to be an alternative substance that could protect people from the harmful effects of acetaminophen.

FXR overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in alcoholic liver disease.

Alcoholic liver disease (ALD), a metabolic liver disease caused by excessive alcohol consumption, has attracted increasing attention due to its high prevalence and mortality. Up to date, there is no effective and feasible treatment method for ALD. This study was to investigate whether Farnesoid X receptor (FXR, NR1H4) can alleviate ALD and whether this effect is mediated by inhibiting absent in melanoma 2 (AIM2) inflammasome activation. The difference in FXR expression between normal subjects and ALD patients was analyzed using the Gene Expression Omnibus (GEO) database. Lieber-DeCarli liquid diet with 5% ethanol (v/v) (EtOH) was adopted to establish the mouse ALD model. Liver histopathological changes and the accumulation of lipid droplets were assessed by H&E and Oil Red O staining. Quantitative real-time PCR, Western blotting analysis and immunofluorescence staining were utilized to evaluate the expression levels of related genes and proteins. DCFH-DA staining was adopted to visualize reactive oxidative species (ROS). FXR was distinctly downregulated in liver tissues of patients with steatosis compared to normal livers using the GEO database, and in ethanol-induced AML-12 cellular steatosis model. FXR overexpression ameliorated hepatic lipid metabolism disorder and steatosis induced by ethanol by inhibiting the expression of genes involved in lipid synthesis and inducing the expression of genes responsible for lipid metabolism. Besides, FXR overexpression inhibited ethanol-induced AIM2 inflammasome activation and alleviated oxidative stress and ROS production during ethanol-induced hepatic steatosis. However, when FXR was knocked down, the results were completely opposite. FXR attenuated lipid metabolism disorders and lipid degeneration in alcohol-caused liver injury and alleviated oxidative stress and inflammation by inhibiting AIM2 inflammasome activation.