Kupffer Cells Research Articles

Hepatoprotective Effect of Corn Silk Extract on Carbonated Alcoholic Herbal Beverages Induced Hepatoxicity in Adult Wistar Rats

Corn silk is the long shiny fibers at the top of an ordinary ear of corn (Zea mays). Corn silk contains phytochemicals of medical benefit such as flavonoids compounds which act as antioxidant agents and has been widely reported possess hepatoprotective effect. The objective of this paper is to evaluate the hepatoprotective effect of corn silk extract on carbonated alcoholic herbal beverages (CAHB) induced hepatoxicity in adult Wistar rats. A total of forty five adult Wistar rats weighing between 200g and 250g were randomly assigned into nine groups of five rats each in a group. Group A was the normal control group (no CAHB administration). Groups B, C, D, E, F, G, H and I were the CAHB intoxicated groups and treated with corn silk extract at different doses. After administering a carbonated alcoholic herbal beverage, there was a substantial increase (p≤0.05) in the mean concentration of liver enzymes (ALP, ALT, ALT), total bilirubin, and direct bilirubin. While those characteristics reversed to values similar to the control after being treated with varying doses of corn silk extract The oxidative stress parameter (SOD, GPX, Catalase, MDA) shown significant increase in group. Histological examination of the liver revealed infiltrate of inflammatory cells, vascular ulceration, periportal infiltration of inflammatory cell, and vascular congestion in a group treated with carbonated alcoholic herbal beverages (CAHB). The only group exhibiting normal hepatocyte morphology and kupffer cell activity was the one administered 200 mg/kg of maize silk extract. Group D showed a similar and more powerful hepatic architecture after receiving only 600 mg/kg of maize silk extract. The hepatoprotective and anti- oxidative effects of corn silk extract were confirmed by the treatment groups (200 mg/kg and 600 mg/kg), which displayed normal hepatocytes with minor vascular congestion, respectively. Corn silk administration lowers a number of the harmful effects of in vivo carbonated alcoholic herbal beverage administration in the liver of Wister rats, according to the findings in this study.

Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

264.9: GSK3β deficiency ameliorates hepatic ischemia-reperfusion injury by regulating necroptosis of kupffer cells.

264.9: GSK3β deficiency ameliorates hepatic ischemia-reperfusion injury by regulating necroptosis of kupffer cells.

YAP activation in liver macrophages via depletion of MST1/MST2 enhances liver inflammation and fibrosis in MASLD.

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH. Genetically modified mice, featuring specific depletion of both Mst1 and Mst2 in macrophages/monocytes, were generated and exposed to a high-fat diet for 12 weeks to induce MASLD. Following this period, livers were collected for histopathological examination, and liver non-parenchymal cells were isolated and subjected to various analyses, including single-cell RNA-sequencing, immunofluorescence and immunoblotting and qRT-PCR to investigate the impact of YAP signaling on the progression of MASLD. Our data revealed that Mst1/2 depletion in liver macrophages enhanced liver inflammation and fibrosis in MASLD. Using single-cell RNA-sequencing, we showed that YAP activation via Mst1/2 depletion upregulated the expressions of both pro-inflammatory genes and genes associated with resolution/tissue repair. We observed that YAP activation increases Kupffer cell populations (i.e., Kupffer-2 and Kupffer-3) which are importantly implicated in the pathogenesis of MASLD/MASH. Our data indicate that YAP activation via Mst1/2 deletion enhances both the pro-inflammatory and tissue repairing functions of Kupffer-1 and -2 cells at least in part through C1q. These YAP-regulatory mechanisms control the plasticity of liver macrophages in the context of MASLD/MASH. Our findings provide important evidence supporting the critical regulatory role of YAP signaling in liver macrophage plasticity and the progression of MASLD. Therefore, targeting the Hippo-YAP pathway may present a promising therapeutic strategy for the treatment of MASH.

Inhibitor of differentiation 3 confers the robust anti-tumor activity of Kupffer cells.

Inhibitor of differentiation 3 confers the robust anti-tumor activity of Kupffer cells.

Purinergic Signaling in Non-Parenchymal Liver Cells.

Purinergic signaling has emerged as an important paracrine-autocrine intercellular system that regulates physiological and pathological processes in practically all organs of the body. Although this system has been thoroughly defined since the nineties, recent research has made substantial advances regarding its role in aspects of liver physiology. However, most studies have mainly targeted the entire organ, 70% of which is made up of parenchymal cells or hepatocytes. Because of its physiological role, the liver is exposed to toxic metabolites, such as xenobiotics, drugs, and fatty acids, as well as to pathogens such as viruses and bacteria. Under injury conditions, all cell types within the liver undergo adaptive changes. In this context, the concentration of extracellular ATP has the potential to increase dramatically. Indeed, this purinergic response has not been studied in sufficient detail in non-parenchymal liver cells. In the present review, we systematize the physiopathological adaptations related to the purinergic system in chronic liver diseases of non-parenchymal liver cells, such as hepatic stellate cells, Kupffer cells, sinusoidal endothelial cells, and cholangiocytes. The role played by non-parenchymal liver cells in these circumstances will undoubtedly be strategic in understanding the regenerative activities that support the viability of this organ under stressful conditions.

Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.

The matrix metalloproteinase MMP14 is a ubiquitously expressed, membrane-bound, secreted endopeptidase that proteolyzes substrates to regulate development, signaling, and metabolism. However, the spatial and contextual events inciting MMP14 activation and its metabolic sequelae are not fully understood. Here, we introduce an inducible, hepatocyte-specific MMP14-deficient model (MMP14LKO mice) to elucidate cell-intrinsic and systemic MMP14 function. We show that hepatocyte MMP14 mediates diet-induced body weight gain, peripheral adiposity, and impaired glucose homeostasis and drives diet-induced liver triglyceride accumulation and induction of hepatic inflammatory and fibrotic gene expression. Single-nucleus RNA sequencing revealed that hepatocyte MMP14 mediates Kupffer cell and T-cell accumulation and promotes diet-induced hepatocellular subpopulation shifts toward protection against lipid absorption. MMP14 co-immunoprecipitation and proteomic analyses revealed MMP14 substrate binding across both inflammatory and cytokine signaling, as well as metabolic pathways. Strikingly, hepatocyte MMP14 loss-of-function suppressed skeletal muscle and adipose inflammation in vivo, and in a reductionist adipose-hepatocyte co-culture model. Finally, we reveal that trehalose-type glucose transporter inhibitors decrease hepatocyte MMP14 gene expression and nominate these inhibitors as translatable therapeutic metabolic agents. We conclude that hepatocyte MMP14 drives liver and inter-organ inflammatory and metabolic sequelae of obesogenic dietary insult. Modulating MMP14 activation and blockade thus represents a targetable node in the pathogenesis of hepatic inflammation.

Activation of α7 nicotinic acetylcholine receptors inhibits hepatic necroptosis and ameliorates acute liver injury in mice.

Acute liver injury (ALI) is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate ALI and investigate its possible mechanisms. ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type (WT), α7nAChR knockout (α7nAChR -/-) and Sting mutation (Stinggt/gt) mice in the presence or absence of a pharmacological selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis and infiltration of immune cells during ALI were assessed. The expression of α7nAChR in liver tissue was increased in LPS/D-Gal induced ALI mice. Compared to the age-matched WT mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacological activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86 hiCD163low), Ly6Chi monocytes (CD45+CD11b+MHCⅡ lowLy6C hi), but increased the resident Kupffer cells (CD45+CD11bintF4/80 hiTIM4 hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR. Our study revealed that activating α7nAChR could protect against LPS/D-Gal induced ALI by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway.

Ameliorative Effects of Teucrium polium Leaves Ethanolic Extract on Liver Histopathology Induced by Eimeria papillata

Background: Teucrium polium is an herb utilized in traditional medicine for its biological activity. In the present study, T. polium leaves ethanolic extract (TPLEE) was investigated for its effects on coccidiosis resulting from Eimeria papillata infection in mice. Methods: In vivo, TPLEE (150 mg/kg) was administered for its antioxidant and hepatoprotective properties. The anticoccidial and anti-inflammatory effects of TPLEE were evaluated by measuring oocyst suppression and assessing liver histopathology, respectively. Result: Indicated that treatment with 150 mg/kg TPLEE led to oocyst suppression percentage of 91.2±4.1, similar to the efficacy of the reference drug amprolium (93.2±3.9) and was associated with a significant decrease in the number of developmental parasitic stages in jejunal sections. Infection with the parasite causes metabolic disturbance, inflammation and liver injury, as evidenced by histopathological changes such as Kupffer cell activation, vacuolated hepatocytes and increases in inflammatory cellular infiltration. In addition, infection led to a significant increase in malondialdehyde (MAD) and nitric oxide (NO) and a significant decrease in superoxide dismutase (SOD) and glutathione (GSH). The TPLEE showed significant hepatoprotective ability by improving the above parameters. TPLEE demonstrated both anticoccidial properties and the ability to alleviate preexisting liver damage caused by Eimeria infection.

Enhanced Maturity and Functionality of Vascularized Human Liver Organoids through 3D Bioprinting and Pillar Plate Culture.

Liver tissues, composed of hepatocytes, cholangiocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells, are differentiated from endodermal and mesodermal germ layers. By mimicking the developmental process of the liver, various differentiation protocols have been published to generate human liver organoids (HLOs) in vitro using induced pluripotent stem cells (iPSCs). However, HLOs derived solely from the endodermal germ layer often encounter technical hurdles, such as insufficient maturity and functionality, limiting their utility for disease modeling and hepatotoxicity assays. To overcome this, we separately differentiated EpCAM+ endodermal progenitor cells (EPCs) and mesoderm-derived vascular progenitor cells (VPCs) from the same human iPSC line. These cells were then mixed in BME-2 matrix and concurrently differentiated into vascular human liver organoids (vHLOs). Remarkably, vHLOs exhibited significantly higher maturity than vasculature-free HLOs, as demonstrated by increased coagulation factor secretion, albumin secretion, drug-metabolizing enzyme (DME) expression, and bile acid transportation. To enhance assay throughput and miniaturize vHLO culture, we 3D bioprinted expandable HLOs (eHLOs) in BME-2 matrix on a pillar plate platform derived from EPCs and VPCs and compared with HLOs derived from endoderm alone. Compared to HLOs cultured in a 50 μL BME-2 matrix dome in a 24-well plate, vHLOs cultured on the pillar plate exhibited superior maturity, likely due to enhanced nutrient and signaling molecule diffusion. The integration of physiologically relevant patterned liver organoids with the unique pillar plate platform enhanced the capabilities for high-throughput screening and disease modeling.

Lipid-associated macrophages’ promotion of fibrosis resolution during MASH regression requires TREM2

While macrophage heterogeneity during metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages during MASH regression is poorly understood. Comparing macrophage heterogeneity during MASH progression vs regression, we identified specific macrophage subpopulations that are critical for MASH/fibrosis resolution. We elucidated the restorative pathways and gene signatures that define regression-associated macrophages and establish the importance of TREM2+ macrophages during MASH regression. Liver-resident Kupffer cells are lost during MASH and are replaced by four distinct monocyte-derived macrophage subpopulations. Trem2 is expressed in two macrophage subpopulations: i) monocyte-derived macrophages occupying the Kupffer cell niche (MoKC) and ii) lipid-associated macrophages (LAM). In regression livers, no new transcriptionally distinct macrophage subpopulation emerged. However, the relative macrophage composition changed during regression compared to MASH. While MoKC was the major macrophage subpopulation during MASH, they decreased during regression. LAM was the dominant macrophage subtype during MASH regression and maintained Trem2 expression. Both MoKC and LAM were enriched in disease-resolving pathways. Absence of TREM2 restricted the emergence of LAMs and formation of hepatic crown-like structures. TREM2+ macrophages are functionally important not only for restricting MASH-fibrosis progression but also for effective regression of inflammation and fibrosis. TREM2+ macrophages are superior collagen degraders. Lack of TREM2+ macrophages also prevented elimination of hepatic steatosis and inactivation of HSC during regression, indicating their significance in metabolic coordination with other cell types in the liver. TREM2 imparts this protective effect through multifactorial mechanisms, including improved phagocytosis, lipid handling, and collagen degradation.

Lipopolysaccharide, arbiter of the gut-liver axis, modulates hepatic cell pathophysiology in alcoholism.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

Both TREM2-dependent macrophages and Kupffer cells play a protective role in APAP-induced acute liver injury

The inflammatory response is a significant factor in acetaminophen (APAP)-induced acute liver injury. And it can be mediated by macrophages of different origins. However, whether Kupffer cells and mononuclear-derived macrophages play an injury or protective role in APAP hepatotoxicity is still unclear. In this study, C57/BL6N mice were performed to establish the APAP acute liver injury model. Intervention experiments were also carried out using clodronate liposomes or TREM2 knockout. We found that APAP overdose triggered the activation of inflammatory factors and enhanced the expression of the RIPK1-MLKL pathway in mice’s livers. Moreover, our study showed that inflammation-related protein expression was increased after clodronate liposome administration or TREM2 knockout. The RIPK1-MLKL-mediated necroptosis was also significantly activated after the elimination of Kupffer cells or the inhibition of mononuclear-derived macrophages. More importantly, clodronate liposomes treatment and TREM2 deficiency all worsen APAP-induced liver damage in mice. In conclusion, the results indicate that Kupffer cells and mononuclear macrophages play a protective role in APAP-induced liver injury by regulating necroptosis. Therefore, macrophages hold as a potential therapeutic target for APAP-induced liver damage.

Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.Graphical

Modulation of mitochondrial dynamism in Kupffer cells impacts systemic metabolism

Modulation of mitochondrial dynamism in Kupffer cells impacts systemic metabolism

Single cell RNA sequencing and spatial transcriptomic to profile Kupffer cells during NASH and liver cirrhosis

Single cell RNA sequencing and spatial transcriptomic to profile Kupffer cells during NASH and liver cirrhosis

Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages

Ethnopharmacological relevanceCoix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. Aim of the studyThis study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. Materials and methodsFemale BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. ResultsCoixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. ConclusionsCoixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes.

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium-activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lmin vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type-specific TMEM16F-deficient mice, the indication is obtained thatTMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host againstListeriainfection. This influence is associated with the capacity of Kupffer cell-expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.

Histological and Physiological Evaluation of Salmonella Spp. Pathogenicity Experimentally Dosed in Male Albino Mice

The research aimed to isolate and diagnose the serological strains of Salmonella spp. that cause typhoid fever, as well as those that cause intestinal inflammations, and to study their histological pathogenesis after experimentally dosed in immunosuppressed male albino mice. The research included 180 blood and stool samples from people with typhoid fever, and 20 samples from people with diarrhea, as well as 30 samples representing the control group. The bacteriological results showed that 26 patients were diagnosed with S. typhi out of 180 patients with typhoid fever, representing 14.4%, and 5 patients were diagnosed with S. typhimurium out of 20 patients with diarrhea, representing 25%. The results of the study showed an increase in the levels of liver enzymes, as the average concentration of the ALT enzyme for the category of patients infected with typhoid, with a recent and confirmed infection with S. typhi, reached 11.283 international units/liter, and the average concentration of the AST enzyme for the same category reached 20.1 international units/liter, compared to the control group. 48 male laboratory mice were used and distributed into 4 groups of 12 mice per group. The first group was the control group that was dosed with physiological solution in an volume of 0.2 ml. The second group was dosed with a suspension of S. typhi bacteria in a volume of 0.2 ml and a concentration of 1×108 colonies/ml. The third group was dosed for a week with the immunosuppressant cyclosporine before and after the experimental infection with a suspension of S. typhi bacteria in a volume of 0.2 ml and a concentration of 1×108 colony/ml. The fourth group was dosed with a suspension of S. typhimurium bacteria in a volume of 0.2 ml and a concentration of 1×107 colony/ml. The mice were dissected one week, two weeks and three weeks after the experimental infection, at a rate of 3 mice per week from each group. The blood was collected and the liver was removed from each mouse. The results showed a slight increase in the ALT enzyme average concentration for the group of mice treated with the immunosuppressant cyclosporine and dosed with S. typhi, reaching 18.57 IU/L, while the group of mice dosed with S. typhimurium was within the limits of the control group and reached 12.24 IU/L. The AST enzyme concentration rate in the control group was 15.136 IU/L, and for the group of mice treated with the immunosuppressant cyclosporine and dosed with S. typhi, it reached 24.74 IU/L, while the concentration for the group of mice dosed with S. typhimurium reached 21.76 IU/L. As for the histological study, the results of the microscopic examination showed the occurrence of many histological lesions in the liver, represented by severe degeneration and acute necrosis, with hypertrophy and sometimes hyperplasia in the hepatocytes, and the loss of chromatin in the nuclei of a number of them, with thickening of the nuclear envelope and sometimes thickening of the nuclei, as well as vacuolation of the cytoplasm in other hepatocytes, with an increase in the number and size of Kupffer cells in the blood sinusoids, which varied in their appearance between narrowed, dilated and congested with blood. It was found that these pathological lesions were more severe in the group of mice treated with the immunosuppressant cyclosporine and dosed with S. typhi.