Histological Changes In Liver Research Articles

Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

Pharmacological effect of Argyrolobium roseum (Camb.) Jaub & Spach extracts against lead-induced toxicity in rats.

Argyrolobium roseum (Camb.) Jaub & Spach (Papilionaceae) is a medicinal plant, cultivated in northern areas of Pakistan. The consumption of trace minerals (lead) is very toxic to the vital organs of the body, therefore the overcome of these minerals is very necessary. In this regard, this study aimed to assess the potential pharmacological effect of aqueous and ethanolic extract of Argyrolobium roseum (Camb.) Jaub & Spach against pb-induced oxidative stress, histological changes in Pb-induced rats' liver and kidney, and anti-inflammatory effect. The metal concentrations in liver and kidney homogenates were measured through atomic absorption spectrophotometer. The antioxidant activity was measured through DPPH and FRAP assay. Pb concentrations were significantly higher in liver and kidney homogenates after injection of Pb acetate was given intraperitoneally (45.2 ± 6.8 and 58.8 ± 7.9, respectively; p < .0001). The level of Pb in liver and kidney homogenates was significantly reduced by aqueous and ethanolic extracts of Argyrolobium roseum (Camb.) Jaub & Spach. The Pb + Aq-600 mg/kg-treated rats exhibited a protective effect on hepatocytes cells against Pb-induced liver injury and restored the cells of the kidney. Pb + Aq-600 mg/kg showed higher antioxidant activity as compared to other treated groups. The highest decreased MDA level was found in liver and kidney homogenate of Pb + Aq-600 mg/kg rats (11.2 ± 1.51 nmol/mg; p < .001) and GSH and CAT levels tended to normal after treatment of Pb + Aq-600 mg/kg in rats. The ALAD, ALT, AST, and ALP level were enhanced and tended to be normal after the Aq-400 and Aq-600 mg/kg treatment in Pb-exposed rats. The result showed that 600 mg/kg Aq + Pb exhibited significant (p < .001) anti-inflammatory activity. The findings of this study concluded that treatment of the aqueous extract of Argyrolobium roseum (Camb.) Jaub & Spach reduces the renal and hepatic damage in Pb-induced rats and it also decreases oxidative stress via improving antioxidant components.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body’s antioxidant defense system, reducing inflammation, and suppressing apoptosis.Graphical

Exposure of zebrafish (Danio rerio) to graphene oxide for 6 months suppressed NOD-like receptor-regulated anti-virus signaling pathways.

Environmental exposure to graphene oxide (GO) is likely to happen due to the use and disposal of these materials. Although GO-induced ecological toxicity has been evaluated before by using aquatic models such as zebrafish, previous studies typically focused on the short-term toxicity, whereas this study aimed to investigate the long-term toxicity. To this end, we exposed zebrafish to GO for 6 months, and used RNA-sequencing to reveal the changes of signaling pathways. While GO exposure showed no significant effects on locomotor activities, it induced histological changes in livers. RNA-sequencing data showed that GO altered gene expression profiles, resulting in 82 up-regulated and 275 down-regulated genes, respectively. Through the analysis of gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we found that GO suppressed the signaling pathways related with immune systems. We further verified that GO exposure suppressed the expression of genes involved in anti-virus responses possibly through the inhibition of genes involved in NOD-like receptor signaling pathway. Furthermore, NOD-like receptor-regulated lipid genes were also inhibited, which may consequently lead to decreased lipid staining in fish muscles. We concluded that 6 month-exposure to GO suppressed NOD-like receptor-regulated anti-virus signaling pathways in zebrafish.

The histopathological changes of liver and testis of Japanese quail chicks fed different levels of dietary L-valine

This experiment was carried out to investigate the histological changes of liver and testis of Japanese quail fed different levels of dietary valine (Val) in low protein diet. A total of 1000 one-day-old Japanese quail chicks (mixed sex) were assigned to five experimental diets including diets containing 7.5, 8.5, 9.5, 10.5 and 11.5 g digestible (dig.) Val/kg diet in a completely randomized design, with 5 replicates of 40 quail chicks per pen. Experimental diets were formulated to be isoenergetic and isonitrogenous (170 g crude protein/kg) to meet nutrients recommendation of growing quails suggested by Brazilian tables. At d 42, quail chicks were slaughtered, and tissue samples were collected and fixed to evaluate the histological indices of liver and testis. High levels of Val, increased (P < 0.05) diameter of liver cell nucleus and liver hepatocytes in both male and female. While 11.5 g Val showed mild hepatosteatosis, bile duct hyperplasia was observed in 10.5 g Val. In 7.5 and 8.5 g Val groups, there was no negative effects on the liver histology. The male quail chicks which fed on diets containing 8.5 g Val had better significant (P < 0.05) reproductive indexes [Tubular differentiation (TDI) and spermatic index (SI)]. In conclusion, the use of high levels of Val (≥ 9.5 g dig. Val/kg diet) during d 0 – 42 of age can lead to histological damage in liver and testis of quail chicks.

HEPATOPROTECTIVE EFFECT OF SEA BUCKTHORN BERRY SEED OIL IN CYCLOPHOSPHAMIDE-INDUCED HEPATIC TOXICITY IN BALB/c MICE

Background: Chemotherapy-induced hepatotoxicity can be mitigated by use of antioxidants, which may help the liver to recover its endogenous antioxidant mechanism. The objective of this study was to determine the effectiveness of sea buckthorn berry seed oil (SBO) in attenuating cyclophosphamide-induced changes in liver enzymes and liver histology in BALB/c mice. Methods: This experimental study was conducted in Physiology Department of Foundation University School of Health Sciences (FUSH), in collaboration with Pathology Department, FUSH and National Institute of Health, Islamabad from Jan 2018 to Jun 2019. Thirty healthy male BALB/c mice were divided into 3 groups of 10 each. Group-1 served as control. Group-2 received cyclophosphamide (25 mg/Kg body weight) intraperitoneally for 10 days. Group-3 was co-administered cyclophosphamide (same dose) with of sea buckthorn berry seed oil (40 mg/Kg body weight) orally for ten days. All animals were sacrificed on 11th day. Serum levels of liver enzymes as liver injury biomarkers were assayed. Liver histopathology was carried out for evidence of hepatic injury and recovery. Results: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) increased significantly in Group-2 (p&lt;0.05). In Group-3, the rise in hepatic injury serum markers was significantly less than Group-2 (p&lt;0.05). Upon histological examination, Group-2 was grade 5 according to Kleiner’s scoring system for steatohepatitis, and had grade 2 sinusoidal dilatation on Rubbia-Brandt grading system. These changes were significantly less in Group-3 (p&lt;0.05). Conclusion: Co-administration of SBO mitigated the CP-induced rise in hepatic injury biomarkers and sinusoidal injury. Pak J Physiol 2023;19(2):20–4

Protective role of Dodonaea viscosa extract against streptozotocin-induced hepatotoxicity and nephrotoxicity in rats

Previous investigations have shown that D. viscosa herbal extract is often used to treat a variety of diseases. Therefore, the purpose of this study was to investigate any additional potential impacts on rat liver and kidney damage induced by diabetes. Streptozotocin (STZ) (60 mg/kg/day) was given as a single dosage to cause type 1 diabetes. After then, diabetic rats received oral doses of D. viscosa for four weeks at 150 and 300 mg/kg/day. Blood, liver, and kidney tissues were collected at the end of the treatment and examined. Analysis was made of the serum lipid profile, liver, and kidney functions, as well as blood biochemistry. Moreover, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), prostaglandin E-2 (PGE-2), and nitric oxide (NO) were estimated in serum. In liver and kidney samples, thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH), as well as the pro-inflammatory cytokines and enzymatic activities of glutathione peroxidase (GPx), glutathione reeducates (GR), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were analyzed. Histological changes in liver and kidney cross-sections were also observed. Our findings demonstrated that D. viscosa dramatically decreased pro-inflammatory indicators in blood, kidney, and liver tissues as well as blood glucose, and restored insulin levels, and lipid profiles. Additionally, it significantly raises the antioxidant enzyme activity SOD, CAT, GPx, and GST, while significantly lowering TBARs levels. The above-mentioned biochemical changes that took place in tissues were further supported by histological alterations. These findings imply that D. viscosa protects against STZ-induced hyperglycemia, aberrant lipid synthesis, and oxidative stress and that these benefits may be mediated by interacting with various targets to increase the levels of antioxidant enzymes in the liver and kidneys. Its mode of action and safety for use as medicine against various metabolic problems caused by diabetes require more research.

Histological changes in liver and kidney of male mice by age after exposure to aluminum chloride.

The informal aluminum industry is increasingly widespread in low- and middle-income countries, especially in Indonesia. Aluminum exposure is a serious public health problem, especially among workers in the informal aluminum foundry sector. Research on aluminum (Al) is important to advance our understanding of its impact on physiological systems. Here, we investigated the effect of exposure to aluminum longitudinal histological changes on the liver and kidneys of male mice. Mice were separated into six groups (4/group): group 1, group 2, group 3 received vehicles, and group 4, group 5, group 6 were administered a single dose of Al at 200mg/kg b.w. by intraperitoneally every 3days for 4weeks. Post-sacrifice, kidneys and liver were isolated for examination. While Al did not impact the body weight gain of male mice across all groups, it caused liver damage including sinusoidal dilatation, enlarged central veins, vacuolar degeneration, and pyknotic nuclei in one-month-old mice. Furthermore, atrophied glomeruli, blood-filled spaces, and disintegration of renal tubular epithelium are evident at one-month-age. By contrast, sinusoidal dilatation and enlarged central veins were found in mice two- and three-months-old, including hemorrhage in mice (two-month-old) and atrophy of glomeruli. Lastly, the kidneys of three-month-old mice displayed interstitial fibrosis and increasing mesenchyme in the glomeruli. In summary, we demonstrated that Al provoked histological changes in the liver and kidneys with Al-treated 1-month mice being the most susceptible.

A polysaccharide from Codonopsis pilosula roots attenuates carbon tetrachloride-induced liver fibrosis via modulation of TLR4/NF-κB and TGF-β1/Smad3 signaling pathway.

The present work reported the extraction, purification, characterization of a polysaccharide from roots of Codonopsis pilosula (CPP-A-1) and its effect on liver fibrosis. The findings exhibited that the molecular weight of CPP-A-1 was 9424Da, and monosaccharide composition were glucose and fructose and minor contents of arabinose. Structural characterization of CPP-A-1 has a backbone consisting of→(2-β-D-Fruf-1)n→ (n ≈ 46-47). Treatment with CPP-A-1 inhibited the proliferation of transforming growth factor-beta 1 (TGF-β)-activated human hepatic stellate cell line (LX-2), and induced cell apoptosis. We used carbon tetrachloride (CCl4) to construct mice model of liver fibrosis and subsequently administered CPP-A-1 treatment. The results showed that CPP-A-1 alleviated CCl4-induced liver fibrosis as demonstrated by reversing liver histological changes, decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) contents, collagen deposition, and downregulated fibrosis-related collagen I and α-smooth muscle actin (α-SMA), and inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and its inhibitor (TIMPs). Moreover, CPP-A-1 improved anti-oxidation effects detected by promoting liver superoxide dismutase (SOD), glutathione (GSH) and Mn-SOD levels, and inhibition of liver malondialdehyde (MDA) and iNOS levels. CPP-A-1 also ameliorated the inflammatory factor (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), and expression of inflammatory factor genes (TNF-α, IL-11 mRNA). In addition, our results showed that CPP-A-1 inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and transforming growth factor-β1 (TGF-β1)/drosophila mothers against decapentaplegic 3 (Smad3) signaling pathways. Furthermore, In vitro tests of LX-2 cells demonstrated that CPP-A-1 not only inhibited α-SMA expression with lipopolysaccharide (LPS) or TGF-β1 stimulation, but also inhibited TLR4/NF-κB and TGF-β1/Smad3 signaling, similar to corresponding small-molecule inhibitors. Therefore, CPP-A-1 might exert suppressive effects against liver fibrosis by regulating TLR4/NF-κB and TGF-β1/Smad3 signaling, our findings support a possible application of CPP-A-1 for the treatment of liver fibrosis.

Efficient prime editing in mouse brain, liver and heart with dual AAVs

Realizing the promise of prime editing for the study and treatment of genetic disorders requires efficient methods for delivering prime editors (PEs) in vivo. Here we describe the identification of bottlenecks limiting adeno-associated virus (AAV)-mediated prime editing in vivo and the development of AAV-PE vectors with increased PE expression, prime editing guide RNA stability and modulation of DNA repair. The resulting dual-AAV systems, v1em and v3em PE-AAV, enable therapeutically relevant prime editing in mouse brain (up to 42% efficiency in cortex), liver (up to 46%) and heart (up to 11%). We apply these systems to install putative protective mutations in vivo for Alzheimer’s disease in astrocytes and for coronary artery disease in hepatocytes. In vivo prime editing with v3em PE-AAV caused no detectable off-target effects or significant changes in liver enzymes or histology. Optimized PE-AAV systems support the highest unenriched levels of in vivo prime editing reported to date, facilitating the study and potential treatment of diseases with a genetic component.

Phytochemical profiling, antioxidant potential and protective effect of leaves extract of tunisian Vitis vinifera autochthonous accessions against acute CCl4-injured hepatotoxicity in mice

Vitis vinifera leaves (VVL) are agro-industrial waste. In the current study, the phytochemical profile of V. vinifera leaves extracts (VVLE) of two Tunisian autochthonous accessions was determined via LC-UV-ESI/MS, and their antioxidant and hepatoprotective properties were also assessed. Mice were pretreated orally with VVLE (7.5, 15 and 30 mg/kg) for 7 days, and then received acutely and by i.p. a solution CCl4 at 12% in sunflower oil (v/v). Serum levels of hepatic markers, oxidative stress indicators in liver tissue and histological changes were assessed. LC-UV-ESI/MS analysis revealed four phenolic compounds identified in both extracts with quercetin-3-O-glucuronide being the dominant constituent (23.32 ± 1.06 vs. 10.24 ± 0.12 mg/g DM, p < 0.05 for wild and cultivated accessions, respectively). The Antioxidant activity revealed a significant difference between the genotypes. Moreover, the VVLE of the wild "Nefza-I" ecotype was the most active based on antioxidant assays. Furthermore, the results showed that pre-treatment, especially with VVLE, of the wild ecotype "Nefza-I", attenuated CCl4-induced acute liver injury in a dose-dependent manner, as demonstrated by the decrease in the activities of hepatic serum function markers. This was also evidenced by a decrease in the levels of lipoperoxidation and histological damage in the liver, as well as a restoration of antioxidant enzyme activities (SOD and catalase) and an increase in the hepatic glutathione content. Our results demonstrate that VVLE possesses protective effects on CCl4-induced liver injury. Overall, the wild ecotype "Nefza-I" extract could serve as an effective protector against CCl4-induced hepatocellular oxidative stress.

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin.

Ethanol-producing dysbiotic gut microbiota could accelerate the progress of non-alcoholic fatty liver disease (NAFLD). Metformin demonstrated some benefits in NAFLD. In the present study, we tested the ability of metformin to modify ethanol-producing gut bacterial strains and, consequently, retard the progress of NAFLD. This 12-week study included forty mice divided into four groups (n = 10); normal diet, Western diet, Western diet with intraperitoneal metformin, and Western diet with oral metformin. Oral metformin has a slight advantage over intraperitoneal metformin in ameliorating the Western diet-induced changes in liver function tests and serum levels of different cytokines (IL-1β, IL-6, IL-17, and TNF-α). Changes in liver histology, fibrosis, lipid content, Ki67, and TNF-α were all corrected as well. Faecal ethanol contents were increased by the Western diet but did not improve after treatment with metformin although the numbers of ethanol-producing Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) were decreased by oral metformin. Metformin did not affect bacterial ethanol production. It does not seem that modification of ethanol-producing K. pneumoniae and E. coli bacterial strains by metformin could have a significant impact on the therapeutic potentials of metformin in this experimental model of NAFLD.

Potential therapeutic action of tauroursodeoxycholic acid against cholestatic liver injury via hepatic Fxr/Nrf2 and CHOP-DR5-caspase-8 pathway.

Cholestasis is a pathophysiologic syndrome with limited therapeutic options. Tauroursodeoxycholic acid (TUDCA) has been employed to treat hepatobiliary disorders and is as effective as UDCA in alleviating cholestatic liver disease in clinical trials. Until now, TUDCA's mechanism of action toward cholestasis remains unclear. In the present study, cholestasis was induced with a cholic acid (CA)-supplemented diet or α-naphthyl isothiocyanate (ANIT) gavage in wild-type and Farnesoid X Receptor (FXR) deficient mice, using obeticholic acid (OCA) as control. The effects of TUDCA on liver histological changes, transaminase level, bile acid composition, hepatocyte death, expression of Fxr and nuclear factor erythroid 2-related factor 2 (Nrf2) and target genes, as well as apoptotic signaling pathways, were investigated. Treating CA-fed mice with TUDCA markedly alleviated liver injury, attenuated bile acids retention in liver and plasma, increased Fxr and Nrf2 nuclear levels and modulated the expression of targets regulating synthesis and transportation of bile acids, including BSEP, MRP2, NTCP and CYP7A1. TUDCA, but not OCA, activated Nrf2 signaling and exerted protective effects against cholestatic liver injury in Fxr-/- mice fed with CA. Furthermore, in both mice with CA- and ANIT-induced cholestasis, TUDCA decreased expression of GRP78 and CCAAT/enhancer-binding protein homologous protein (CHOP), reduced death receptor 5 (DR5) transcription, caspase-8 activation, and BID cleavage, and subsequently inhibited activation of executioner caspases and apoptosis in liver. We confirmed that TUDCA protected against cholestatic liver injury by alleviating BAs burden of dually activating hepatic Fxr and Nrf2. Moreover, inhibiting CHOP-DR5-caspase-8 pathway contributed to the anti-apoptotic effect of TUDCA in cholestasis.

Development of mouse models with restricted HLA-B∗57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury

Flucloxacillin (FLX)-induced liver injury is immune-mediated and highly associated to HLA-B∗57:01 expression. Host factors leading to drug-induced liver injury are not yet well understood. Characterize invivo immune mechanisms determining the development of CD8+ T cells reactive to FLX in animals expressing the risk human leukocyte antigen (HLA) allotype. HLA-B∗57:01 transgenic mice (Tg) or Tg strains with H2-KbDb knockout (Tg/KO) or H2-KbDb/PD-1 double knockout (Tg/DKO) were treated with drug and/or anti-CD4 antibody. Drug-induced liver injury was evaluated on the basis of liver enzyme and histologic changes at day 10 of treatment. FLX-reactive CD8+ T cells were characterized invitro by release of effector molecules on drug restimulation, gene expression, and flow cytometry analysis, and functionality tested for hepatic cytotoxicity. CD8+ T-cell responses to FLX in Tg were dependent on both HLA and mouse major histocompatibility complex I presentation and invivo priming. Eliminating H2-KbDb in Tg/KO to allow exclusive presentation of FLX by HLA resulted in a less robust drug-specific CD8+T-cell response unless CD4+ cells, including regulatory T cells, were depleted. Treatment of Tg/KO with anti-CD4 antibody and FLX led to subclinical liver inflammation associated with an increase in PD1+CD8+ T cells in the lymphoid organs and liver. Impaired PD-1 expression in Tg/DKO led to liver histopathologic and transcriptional alterations but without hepatic enzyme elevations. Moreover, effector lymphocytes accumulated in the liver and showed FLX-dependent hepatic cytotoxicity invitro when tolerogenic liver cells were depleted. In our invivo models, FLX primes CD8+ T cells to recognize drug presented by HLA-B∗57:01 and murine major histocompatibility complex I. HLA-B∗57:01-dependent CD8+ T-cell reaction to FLX is limited by the presence of CD4+ cells, presumably regulatory T cells, and PD-1 expression. Tolerogenic hepatic cells limit clinical disease through PD-L1 or additional unexplored mechanisms.

Arginine vasopressin deficiency and conivaptan (a V1a-V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis.

Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) and collagen. Previous work in liver cirrhotic (CCL4 -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-β and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.

English

Pesticides especially insecticides are widely used in the field of agricultural development all over the world to increase crop production. Moreover, exposure to such compounds does not only influence the intended targets but also induces adverse impacts on a number of unintended targets in animals. This research aimed to determine the toxic impacts of lufenuron (an insecticide) on the health status of fish in terms of measurement of oxidative stress, antioxidant enzymes, DNA damage and histopathological changes in Nile tilapia (Oreochromis niloticus) exposed to different concentrations. For this purpose, Oreochromis niloticus fish, weighing about 75-80g were arbitrarily separated into four different groups and then exposed to lufenuron @ 0.7, 1.2 and 1.7µg/ L for 39 days. The results showed that the fish exposed to the pesticide had significant changes in oxidative stress, antioxidant profile in gills and percentile rate of DNA damage in different visceral organs including liver, kidney, and gills. Results of light microscopic investigations indicated different histological changes in liver (necrosis of hepatocytes, degeneration of hepatocytes, vacuolar degeneration and congestion), gills (necrosis of lamellar epithelial cells, telangiectasia, and atrophy of secondary lamellae), heart (congestion, necrosis of neurons, microgliosis and intracellular edema), brain (congestion, myofibrosis, neutrophilic and myocarditis) and kidneys (necrosis of renal tubules, widening of urinary space, necrosis of renal tubular epithelial cells). A significantly escalate in oxidative stress while lower quantity of antioxidant biomarkers was documented in experimental fish. The findings of this study suggest that long-term exposure to lufenuron has negative health effects via induction of DNA damage, increased oxidative stress, lowering of enzymatic antioxidants profile and histological lesions in visceral organs of Nile tilapita (Oreochromis niloticus).

Fermentation of pomegranate juice by lactic acid bacteria and its biological effect on mice fed a high-fat diet

This study investigated the ability of Lactiplantibacillus paraplantarum CRL2051 and Lactiplantibacillus plantarum CRL2030, two lactic acid bacteria isolated from fruits, to ferment pomegranate juice to produce beverages with extended shelf life and functional properties. Lactic acid bacteria consumed glucose and fructose as carbon sources, producing mainly lactic acid. Both strains were initially grown in juice at 30 °C for 48 h, then refrigerated at 4 °C for 28 days. During fermentation and cold storage, the total phenolic content and antioxidant capacity were conserved in fermented pomegranate juices. The functionality studies of the fermented beverages administered to C57BL/6 mice fed a high-fat diet were evaluated over 6 weeks. Pomegranate juice supplementation led to a marked improvement in glucose and triglycerides serum profile, which decreased around 40% and up to 48%, respectively, and counteracted fat deposition and body weight gain. The high-fat diet treatment significantly incremented the aspartate aminotransferase activity in the liver, whereas fermented pomegranate juice consumption slightly reduced it. Liver histological changes associated with a high-fat diet were significantly reverted in juice-treated animals. Our findings evidenced the biological benefits of a novel functional beverage obtained by lactic fermentation of pomegranate juice; this functional drink may protect against weight gain, liver damage, and dyslipidemia induced by a high-fat diet consumption.

Synthesis of silver nanoparticles using aqueous leaf extract of Premna esculenta and in vivo evaluation of its hepatoprotective activity in Swiss albino male mice

In this study, silver nanoparticles (PE-AgNPs) were synthesized using Premna esculenta (PE) leaf extract, characterized by UV, TEM, TEM-EDX, XRD, DLS, and ICPOES studies. AgNPs were found to be stable at −35 mV with 26.157 ppm concentration. AgNPs were found triangular in shape with an average size of about 44 nm. Hepatoprotective activity was assessed in animal model using silymarin as standard drug. Biochemical parameters (serum AST, ALT, γGT, ACP, and ALP), inflammatory markers (IL 1β, IL 17, TNF α, and IL 10), and antioxidant markers (GSH, SOD, Catalase, and LPO) were assayed. Liver tissue was processed for histological analysis. Induction of hepatotoxicity increases AST, ALT, γGT, ACP, ALP, IL 10, LPO, and decreases IL 1β, IL 17, TNF α, GSH, SOD, and Catalase. PE-AgNPs treatment significantly decreases IL 10, LPO while IL 1β, IL 17, TNF α, GSH, and SOD were increased in animals. PE-AgNPs partially recovered CCl4-induced changes in liver histology.

Morphological and Histological Changes in Liver and Lung of mice and Their Embryos Administred with Parkizol Drug

Results expressed the pathological effects through visual microscopical and Histological examination of parkizol in liver and Lung of pregnant mice and their embryos were administered on the7th day of pregnancy as till the18th day of pregnancy. The administration of parkizol doses induced behavioral changes in the form of drowsiness, sluggish movement, mice become isolated, and were consumed less food and water. Abortions recorded 8%,10%and55% following the doses 250,350and450mg/kg b.w., respectively. Death of some pregnant mice occurred at the 16th and 17th day of pregnancy following the dose450 mg/kg b.w., Lesions seen on organs of pregnant mice and included hepatotoxic changes (congestion, vacuolar degeneration and coagulative necrosis of hepatocytes, dilatation of sinusoids .Also inflammation that covered pulmonary changes (emphysema, edema, hyperplasia of bronchial associated lymphoid tissue. Inflammation and hypertrophy of smooth muscles in the walls of blood vessels);The abortion percentages were48%,63% and89% caused by the doses 250,350 and 450mg/kg b.w., respectively. Malformations were noted on encephalocele, encephalomyelocele, anencephalia, displacements of the ears and eyes, cleft palate, aberrations of the vertebral column, shortening and thickening of the limbs, and defects of the tail. The lesions were observed on organs of the fetus included haphazard arrangement of the hepatocytes, vacuolar degeneration and coagulative necrosis of hepatocytes, dilation of the hepatic sinusoids; congestion, hemorrhage, edema and inflammation of the lungs. These results supported the putative pathological effect of parkizol in liver and lung of pregnant mice and their embryos.

Ginsenoside Rg1 and Re alleviates inflammatory responses and oxidative stress of broiler chicks challenged by lipopolysaccharide

Previous study showed that ginsenoside Rg1 (Rg1) and ginsenoside Re (Re) alleviated growth inhibition of broiler chicks with immune stress. The aim of this study was to investigate the effect of Rg1 and Re on inflammatory responses, oxidative stress, and apoptosis in liver of broilers with immune stress induced by lipopolysaccharide (LPS). Forty broiler chicks were randomly divided into 4 groups, each group consisting of 10 chickens. The model group, Rg1 group, and Re group were received continuously interval injection of 250 μg/kg body weight LPS at the age of 12, 14, 33, and 35 days to induce immune stress. Control group was injected with an equivalent amount of sterile saline. Then broilers in Rg1 group and Re group were given 1mg/kg body weight Rg1 and Re intraperitoneally 2 h after the LPS challenge respectively. Blood samples were collected for the detection of hormone levels, inflammatory mediators, and antioxidant parameters. Hepatic tissues were taken for pathological observation. Total RNA was extracted from the liver for real-time quantitative polymerase chain reaction analysis. Our results showed that Rg1 or Re could alleviate histological changes of liver, reduce production of stress-related hormones, inhibit inflammatory responses, and enhance antioxidant capacity in broilers challenged by immune stress. In addition, Rg1 or Re treatment upregulated mRNA expression of antioxidant-related genes and downregulated mRNA expression of inflammation-related factors and apoptosis-related genes in the liver of immune-stressed broilers. The results suggest that the plant extracts containing Rg1 and Re can be used for ameliorating hepatic oxidative stress and inflammation and controlling immune stress in broiler chicks.