Kupffer Cell Hyperplasia Research Articles

Study of urologic exposure dose in selective organ's cell & behavior of Wistar rats

BackgroundRadiologic fluoroscopy procedures have been imposing considerable exposure dose to staff with serious consequences relative to dose quantity which is still continuing as challenge of studies, hence the aims were to assess the animal behavior, quantify blood components and red blood cells morphology after exposure to x-ray urologic fluoroscopy doses (0.3, 0.8, 1.8 and 2.5 mSv). Methodsurologic exposure doses measured by TLDs chips and TLD reader Model 5500 from selected hospitals. These doses used to expose Wister male rats weighted (275 ± 2.0 g). The collected data were animal behavior, quantity of blood components and cellular changes in RBCs, kidneys, liver & testicles then analyzed by SPSS- 20 (SPSS Inc., Chicago, IL, USA) Resultsshowed that a dose of 2.5 mSv decreased significantly (p value = 0.00) the motor activity of rats. and the blood components decreased as follows: WBC (30.2%), Lymphocytes (40%.0), Neutrophils (35.7%), RBC (37.9%), MCV (32.2%) and RCDW (31.5%). At exposure dose of 0.3 mSv a mild morphological changes as circular shape deformity and loss of bi-concavity of RBCs. At 0.8 mSv RBCs diameter increment (10 ± 0.4 μm) and formation of spikes. At 1.8 mSv RBC underwent anisocytosis and poikilocytosis. While at 2.5 mSv the RBC showed intensive spikes, clustering and some underwent hemolysis. Morphological changes were induced also, at 2.5 mSv for the followings: The renal cortex showed bleeding & congestion at 2.5 mSv. The Renal medulla showed bleeding at 2.5 mSv. The liver texture showed bleeding and congestion with two nuclei- Kupffer cells hyperplasia, ballooning of hepatocytes with Acidophilic bodies at 2.5 mSv. the testicles tissues developed congestion and bleeding. Conclusionfluoroscopic urologic exposure dose can induce significant behavioral, RBCs changes and reduction in blood components.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing(NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

Toxicity assessment of perovskite nanocomposites: In vivo study.

Perovskite solar cells display potential as a renewable energy source because of their high-power conversion efficiency. However, there is limited understanding regarding the potential impact of perovskite on human health and the ecosystem. In this study, two sets of male Wistar albino rats received 35 injections of perovskite composite at a dosage of 0.372mg/kg body weight. The animals underwent thorough examinations, encompassing morphometric, hematological, biochemical, histological, and behavioral analyses. Liver, kidney, and testis biopsies were processed and examined histologically. Additionally, two groups of mice (perovskite-treated and control mice, each with n = 10) underwent three behavioral tests: the Elevated Zero Maze test, Marble Burying test, and Light-Dark Box test. Perovskite-treated rats displayed a significant increase in levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol, creatinine, blood urea nitrogen, white blood cells, and platelets. However, total bilirubin levels decreased, with no significant alteration in albumin values. Furthermore, exposure to perovskite composite resulted in a slight decrease in lactate dehydrogenase and red blood cell count. Histopathological examination revealed hepatic hydropic degeneration, Kupffer cells hypertrophy and hyperplasia, and renal hydropic degeneration, while testicular tissues remained unaffected. Moreover, behavioral changes were observed in perovskite-treated mice, including depression, anxiety, and compulsive burying activity. These findings suggest that exposure to perovskite can lead to significant hematological and biochemical changes, as well as hepatorenal histopathological alterations and behavioral changes. Additionally, chronic exposure to perovskite materials may induce structural and functional alterations in vital organs.

The Lasting Effects of COVID-19 on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

It is estimated that around 30% of thepopulation living in Western countries has metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression toward inflammation and irreversible fibrosis metabolic dysfunction-associated steatohepatitis (MASH). With inflammation being a key component of the transition to MASH, it raises the question of whether the ongoing COVID-19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of MASLD. Specifically, it remains unclear if the potential chronic sequelae of COVID-19 in patients who recovered from it may increase the predisposition for MASH. Since MASH maintains a high risk for hepatocellular carcinoma, liver failure, and the need for a liver transplant, the potential additive effects of COVID-19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID-19 could have chronic sequelae that affect the progression of MASLD pathogenesis. It was hypothesized that severe cases of COVID-19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes in the liver, similar to those seen in MASH. A scoping review of the literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug-induced liver injury (DILI), and hypoxia seen in COVID-19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of MASLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, gastrointestinal tract, portal system, or systemic circulation. Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes were unlikely, but the direct viral insult of cholangiocytes was a potential complication. High serum levels of IL-1, TNF-a, and MCP-1, in COVID-19 were found as potential risk factors for MASH development. Hypoxia, altered lipid metabolism, and iatrogenic DILI were also proposed as potential precipitators of MASH development. Notably, lasting changes in gut microbiome were also frequently observed and correlated closely with those seen in MASH.

Hydroxychloroquine Toxicity in the Vital Organs of the Body: In Vivo Study.

Hydroxychloroquine (HCQ) toxicity can adversely affect vital organs, cause pathologic ocular damage, and can have direct cardiovascular effects. This study aims to identify the biochemical, hematological, and histological alterations of the vital organs associated with the effects of HCQ. Male albino rats were exposed to the equivalent of HCQ therapeutic doses given to human patients being affected by malaria, lupus erythematosus, and COVID-19. The animal blood samples were subjected to hematological analysis, biochemical analysis, liver function tests, kidney function tests, and cardiac biomarkers. Liver, kidney, heart, spleen, and testis biopsies were subjected to histological examination. HCQ significantly lowered the values of erythrocytes, hemoglobin, hematocrit, platelets, leucocytes, and lymphocytes but significantly increased the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, alkaline phosphatase, lactate dehydrogenase, cholesterol, and chlorine ions. The renal tissues of HCQ-treated animals demonstrated glomerular fragmentation, partial atrophy degeneration, renal tubules hydropic degeneration, hyaline cast formation, and interstitial edema formation. Additionally, the heart exhibited myofiber necrosis, myolysis, wavy appearance, disorganization, and disarray. The testicular tissues also demonstrated spermatocyte degeneration, spermatogenic cell sloughing, testicular interstitial edema, and occasional spermatogenic arrest. Additionally, the spleen showed a decrease in the number and size of the white pulp follicles, a decrease in the number of apoptotic activity, and a decline in the number of T-rich cells. However, the red pulp demonstrated a diffuse decline in B rich-lymphocytes and macrophages. The liver was also the least affected but showed Kupffer cell hyperplasia and occasional hepatocyte dysplasia. The results indicate that chronic exposure to HCQ could alter the structures and functions of the vital organs.

Biochemical Response and Histopathologic Alterations in Papyrocranus afer from Banegbe River, Delta State, Nigeria

Aim: This study investigated the effects of pollutants on the biochemical and histopathological components of Papyrocranus afer obtained from the Banegbe River at different locations (upstream, middle-stream, and downstream). The effect of the pollutant on the checked were, levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood samples of the fishes and the histopathologic alterations of the gills and liver of the fishes. 
 Methodology: The gills and liver tissue of the fish were collected and processed using routine histologic techniques for fixing and embedding in paraffin and staining sections with hem eosin. All the indices of the enzyme tests were estimated with the aid of Randox Diagnostic Test Kits following the manufacturer’s methods. 
 Results: Evaluation of the plasma enzymes showed significant increases (p<0.05) in plasma ALT, AST, and ALP activity in all the sampled points of Banegbe River when compared to the control 1 (Orogodo river) with middle-stream having significant (p<0.05) higher concentrations when compared to down-stream and up-stream. The main alterations observed in the liver of the fish at the Banegbe River were Kupffer cell hyperplasia and focal necrosis of the liver. While the gills showed alteration of the structure of the epithelium, hyperplasia of the epithelium of the primary lamella, epithelial lifting, vacuolization, alteration of the structure, and occurrence of aneurysms in the secondary lamella, all these alterations were as a result of pollutant in the river. Control 1 showed normal parenchymal cells of the liver and normal gill structure. 
 Conclusion: The increase in enzyme activities suggests leakage of these enzymes from the liver cytosol into the bloodstream as a result of liver damage by contaminants. From our results, it can be concluded that the Banegbe River is polluted as a result of effluents channeled in the river by industries within the environs.

Biochemical and histopathological changes in livers of rats poisoned with aluminum phosphide and treated with carrot extract.

The experimental studies of Aluminum Phosphide (AP) poisoning in rats revealed several clinical and pathological signs such as hemorrhage, sinusoidal dilatation, bile stasis, centrilobular necrosis, Kupffer cell hyperplasia, infiltration by mononuclear cells, and fatty infiltration in the liver tissues. This paper aimed to show the impact of carrots on the toxic effect of AP on the livers of adult rats (female). To investigate some biochemical and histopathological changes effects of AP in rats, sixty white female rats were equally divided into four groups, the first group (G1) was administered orally with 3mg/kg/ body weight of AP, the second group (G2) was orally treated with AP and 10% carrot extract at the same time. The third group (G3) administrated 10% carrot extract only. The fourth (G4) group was the negative control and was treated with distilled water only. The experiments continued for a month at the animal house of the Veterinary Medicine College of Baghdad University. The results revealed that high levels of liver enzymes and bilirubin were induced in G1 with decreasing total protein levels. The pathological examination revealed the presence of marked proliferation of Kupffer cells in G1 livers. However, the G2 group showed slight infiltration of lymphocytes in sinusoids. The pathological changes in the livers of G3 group showed slight cloudy swelling in hepatocytes compared with the normal texture of hepatocytes in G4. The data of this experiment showed that treatment with carrot extract significantly decreases the elevation in the level of liver function enzymes in animal poisoned with AP. In addition, treatment with carrot extract reduces the severe damage in the hepatic tissue that occurred in rats treated with AP only. In general, it could be concluded that treatment with carrot extract provides a remedial effect against the hepatotoxicity that is resulted from exposure to AP.

Salmonella Hepatitis and Colitis A case report

Salmonella hepatitis it’s a rare yet occasionally reported complication of Salmonella infection. The pathophysiological mechanism by which the infection causes liver damage is not completely known. Its cardinal clinical characteristic is jaundice, hepatosplenomegaly, the usual transaminase range is between 300-1000 U/L and an ALT/DHL ratio < 4 is characteristic, which is useful for its distinction from viral hepatitis. Histologically, Kupffer cell hyperplasia and typhoid nodules are the characteristic findings. The prognosis is good with treatment for the infection, however a mortality of up to 20% has been reported.

Toxoplasma gondii-derived antigen modifies tumor microenvironment of Ehrlich solid carcinoma murine model and enhances immunotherapeutic activity of cyclophosphamide

Pathogen-based cancer vaccine is a promising immunotherapeutic weapon to stimulate cancer immunosuppressive state. Toxoplasma gondii is a potent immunostimulant, and low-dose infection was linked to cancer resistance. Our goal was to evaluate the therapeutic antineoplastic activity of autoclaved Toxoplasma vaccine (ATV) against Ehrlich solid carcinoma (ESC) in mice in reference to and in combination with low-dose cyclophosphamide (CP), a cancer immunomodulator. Mice inoculation with ESC was followed by applying different treatment modalities including ATV, CP, and CP/ATV. We evaluated the impact of the different treatments on liver enzymes and pathology, tumor weight, volume, and histopathological changes. Using immunohistochemistry, we evaluated CD8+ T cell, FOXP3+ Treg, CD8+/Treg outside and inside ESC, and angiogenesis. Results showed significant tumor weights and volumes reduction with all treatments with 13.3% inhibition of tumor development upon combined CP/ATV use. Significant necrosis and fibrosis were noted in ESC by all treatments with improved hepatic functions versus non-treated control. Although ATV was almost equivalent to CP in tumor gross and histopathology, it promoted an immunostimulatory activity with significant Treg cells depletion outside ESC and CD8+ T cells infiltration inside ESC with higher CD8+ T/Treg ratio inside ESC superior to CP. Combined with CP, ATV exhibited significant synergistic immunotherapeutic and antiangiogenic action compared to either treatment alone with significant Kupffer cells hyperplasia and hypertrophy. Exclusively, therapeutic antineoplastic and antiangiogenic activity of ATV against ESC was verified that boosted CP immunomodulatory action which highlights a novel biological cancer immunotherapeutic vaccine candidate.

Morphological changes in liver of wistar rats induced by Gold Kushta

Objective: To observe hepatic changes induced by Gold Kushta. In our study the histopathological effects of Gold Kushta was seen in livers of Wistar rats. Study Design: Experimental study. Setting: Department of Pathology, Sahiwal Medical College, Sahiwal. Period: 1st July 2019 to 31st Dec 2019. Material & Method: Total of 28 wistar rats of 6 – 8 weeks of age and weighing 200 – 250 grams which were then randomly divided into 4 groups each containing 7 rats. The groups were labelled as G I, II, III and IV. These groups were given preparations of gold in the form of kushta for a period of 8 weeks. The gold kushta was given in the form of pellets. Group I was taken as Control, G II was given single dose kushta 0.15 mg and G III was given double dose kushta 0.3mg on alternate days. Group IV was given a single dose of BSA (bovine serum albumin) 75mg (250mg/kg body wt) at the start of experiment and Gold kushta 0.3 mg on alternate days. Histopathological changes were then seen in lobules, sinusoids, kupffer cells and central veins of livers of wistar rats. Results: The histological examination of liver showed sinusoidal congestion and central vein congestion, apoptosis, necrosis and hydropic degeneration as common features. In addition fatty degeneration, inflammation and kupffer cell hyperplasia were also seen in few cases. These changes were observed in all the above groups except group G I serving as control. More changes were seen in high dose groups and the groups given BSA inj. (Group II, III and IV). Conclusion: Thus, indigenous preparations of gold kushta have detrimental effects over livers of wistar rats and are thus hepatotoxic.

HEPATOTOXICOPATHOLOGY EVALUATION OF DIMETHYLFORMAMIDE (DMF) ON MALE ALBINO RATS LIVERS

This experiment was aimed to investigate the Toxicopathological effect of N, N-Dimethylformamide (DMF) (1/10LD50) on the adult male rats' liver. Sixteen adult male rats were used in this experiment. After acclimatization for two weeks, they were divided equally into two groups as follows: Group-C-control: Normal diet and water for 30 days (n=8 rats).Group-T1: DMF 645.5mg/kg. B.W as 1/10LD50 for30 days ( n=8rats ) , after thirty days collected blood for liver enzymes analysis then all animals killed at the end of the experiment and the liver samples saved at 10% formalin for histopathological preparation. The results showed that serum liver enzymes (ALP, ALT, and AST) concentrations of adult male rats after thirty days of oral DMF administration were significantly different (P<0.05) from the control group. Histopathological changes of group 1/10 LD50 (T1) group appear enlargement of hepatocytes with mild degeneration and mild hyperplasia of kupffer cells, and focal infiltration of inflammatory cells mainly lymphocytes in the portal area and a large area of necrosis.

S3137 Post-COVID-19 Cholestatic Hepatitis

Introduction: Coronavirus Disease 2019 (COVID-19) caused by SARS-COV-2 has led to a global crisis of unprecedented reach and proportion. In addition to the pulmonary consequences, the incidence of liver injury is increasingly being reported. Understanding the hepatotropism of SARS-COV-2 is of paramount importance as it can lead to a severe COVID-19 course. This case details a unique presentation of cholestatic hepatitis likely a sequela of a severe SARS-COV-2 infection in our patient. Case Description/Methods: A 49-year-old lady with a history of seizure disorder, migraines, hypertension, and recent six-week ICU admission for COVID illness requiring mechanical ventilation (ECMO), presented to our gastroenterology clinic for a post-discharge follow-up. During admission, she consistently had an abnormal elevation of liver enzymes (Peak ALP 2000, AST, ALT 300, Bilirubin 2.5). MRCP was normal and a liver biopsy showed marked intralobular bile duct injury showing severe cytologic atypia, periductal edema, periductal and intraductal neutrophilic, and lymphocytic inflammation and marked ductular reaction, focal mild hepatocellular cholestasis, Kupffer cell hyperplasia. She had no prior history of chronic liver disease and LFT was normal at baseline. Post discharge LFT showed alkaline phosphatase of 1514 with total bilirubin 1.4. Infective (Hepatitis A, B, C panel), Inflammatory/Autoimmune (ANA, ASMA, AMA, P-ANC, Anti-SLA/LP, Anti ds-DNA, ALKM-1, and ALKM-3) workup was negative. Repeat imaging with USG and MRI was unremarkable. She received a course of prednisone after discharge with no improvement in LFT, it was tapered off. She is currently asymptomatic 6 months after acute illness but continues to have persistently elevated liver enzymes with a gradual downtrend with the latest being ALP 490, AST 86, ALT 95, and T. Bilirubin 0.8. Discussion: We describe a unique case of post-COVID-19 cholestatic hepatitis with persistently elevated liver biochemistry with unclear etiology despite extensive workup. It could be a confluence of Secondary Cholangitis in Critically Ill Patients (SSC-CIP) and direct hepatic injury from COVID-19. Further data is needed to understand the patterns of liver injury due to COVID and the development of possible treatment for this newly described condition associated with the virus.

S3272 A Potential New Use for Tocilizumab: A Case of Refractory Checkpoint Inhibitor Hepatitis

Introduction: Immune checkpoint inhibitors (CPI) are becoming increasingly common treatment options for several types of cancers. While their use in cancer treatment is very promising, these medications are not without side effects. Specifically, these drugs are commonly associated with hepatic adverse events, including auto-immune hepatitis (AIH). In fact, in one study, AIH was found in approximately 5% of people treated with a CPI. While we know that CPI hepatitis is a potential outcome of treatment with CPIs, we have yet to establish the best treatment options for this adverse event. Based on expert opinion, the recommended course of treatment involves high dose steroids and immunomodulators if needed. There is not, however, much literature on management of CPI hepatitis that is refractory to the typical treatments, though use of tocilizumab has shown some success previously in treatment of immune-related adverse events secondary to CPIs . Case Description/Methods: A 35 y.o. female with recurrent right renal cell carcinoma, status-post resection with nephrectomy, on palliative treatment with nivolumab/ipilimumab, presented to the hospital for further evaluation of elevated liver function tests (LFT) and an abdominal MRI concerning for hepatitis. At time of admission, she was on her 3rd week of steroids, started with concern for drug-induced autoimmune hepatitis due to her checkpoint inhibitor (CPI) treatment. At admission, she was started on IV steroids and mycophenolic acid. LFTs and bilirubin continued to rise despite several days of this treatment and she was given a dose of rituximab. Liver biopsy was obtained which was consistent with CPI induced hepatitis. LFTs and bilirubin continued to rise and tocilizumab was given. 4 days after that treatment, AST and ALT were nearly half their pretreatment values and bilirubin began downtrending. At this point, the patient was stable enough for discharge with very close follow up (Figure). Discussion: Studies from 2019 reveal that 43.68% of all people with cancer in the United States are eligible for CPI therapy. This number translates to 7.9 million patients who are potentially eligible for CPI therapy. With the incidence of severe CPI hepatitis suspected to be up to 20% of all people taking CPIs, this equates to 1.58 million people of whom could be affected. More studies need to be done to address treatment for refractory auto-immune CPI hepatitis, and to better understand the underlying pathogenesis in this rapidly growing population.Figure 1.: Liver biopsy with significant lobular hepatitis, loss of zone 3 hepatocytes, acidophil bodies, and Kupffer cell hyperplasia consistant with checkpoint inhibitor auto-immune hepatitis.

Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.

SummaryLiver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to inflammation. Here, we present an induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection. We used this platform to show robust EBOV infection, with characteristic ultrastructural changes and evidence for viral replication. Transcriptomics analysis revealed a delayed response with minimal early transcriptomic changes, followed by a general downregulation of hepatic function and upregulation of interferon signaling, providing a potential mechanism by which hepatocytes participate in disease severity and liver damage. Using RNA-fluorescence in situ hybridization (FISH), we showed that IFNB1 and CXCL10 were mainly expressed in non-infected bystander cells. We did not observe an inflammatory signature during infection. In conclusion, iPSC-HLCs are an immune competent platform to study responses to EBOV infection.

Haematological and hepatho-renal effect of cashew nut oil on male Wistar rats

The aim of this study was to evaluate the biosafety of Anacardium occidentale (cashew) nut oil using male Wistar rats as model. Cashew nut oil was extracted from cashew nuts with the aid of a Soxhlet apparatus using n-hexane as solvent. Twelve male Wistar rats were randomly assigned to four groups labeled I, II, III and IV (3 rats per group). Group I served as the control group and were administered distilled water. Group II received 1.53 mL/kg of the nut oil; group III received 4 mL/kg of the nut oil while group IV received 8.13 mL/kg of the nut oil. The administrations were via the oral route. Blood samples were collected weekly for haematological examination. At the end of four weeks study period, the rats were anaesthetized and the liver and kidneys were removed for histological examination. The haematological result showed slight deviation from the normal in packed cell volume (52%), total white blood cell count (9.38 x 103/mm3) and lymphocyte count (58.17%) in Wistar rats administered 4 to 8.13 mL/kg of the cashew nut oil, respectively yet no visible compromise of the immune system was observed. Histological analysis; however, revealed some hepatocyte morphological lesions including mild microvesicular steatosis, kupffer cell hyperplasia, shrinkage of glomeruli, glomerular distortion, necrotic renal tubules, severe congestion and atrophy of renal tubules in rats fed 8.13mL/kg of the nut oil. In conclusion, the cashew nut oil was responsible for hepatic parenchymal and matrix alteration in wistar rats administered 8.13 mL/kg of cashew nut oil.

The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

The Lasting Effects of COVID‐19 on The Progression of Non‐Alcoholic Fatty Liver Disease

It is estimated that around 30% of the Western population has non‐alcoholic liver disease (NAFLD); a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression towards inflammation and irreversible fibrosis (non‐alcoholic steatohepatitis, or NASH). With inflammation being a key component of the transition to NASH, it raises the question of whether the ongoing COVID‐19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of NAFLD. Specifically, it remains unclear if potential chronic sequelae of COVID‐19 in recovered patients may increase predisposition for NASH. Since NASH maintains a high risk for hepatocellular carcinoma, liver failure, and need for liver transplant, potential additive effects of COVID‐19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID‐19 could have chronic sequelae that affect the progression of NAFLD pathogenesis. It was hypothesized that severe cases of COVID‐19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes of the liver, similar to those seen in NASH.A scoping review of literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug‐induced liver injury, and hypoxia seen in COVID‐19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of NAFLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, GIT, portal system, or systemic circulation.Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes was unlikely, but direct viral insult of cholangiocytes was a potential complication. High serum levels of IL‐1, TNF‐a, and MCP‐1, in COVID‐19 were found as potential risk factors for NASH development. Hypoxia, altered lipid metabolism, and iatrogenic drug‐induced liver injury were also proposed as potential precipitators of NASH development. Notably, lasting changes in gut microbiome were also frequently observed, and correlate closely with those seen in NASH.It was concluded that future research should target the gut microbiome, hyperinflammation, and hepatobiliary congestion as integral components of potentially accelerated NASH development NAFLD‐comorbid patients following COVID‐19 recovery.

Lipid profiles, hematological parameters and histopathological analysis of CCl4-intoxicated wistar albino rats treated with n-butanol extract of Ficus glumosa leaves

Abstract. Abu MS, Yakubu OE, Onuche JI, Okpe O. 2022. Lipid profiles, hematological parameters and histopathological analysis of CCl4-intoxicated wistar albino rats treated with n-butanol extract of Ficus glumosa leaves. Cell Biol Dev 6: 6-12. This research critically assessed the effect of the n-butanol fraction of methanol extract of Ficus glumosa Delile leaves on serum lipid profile, hematological parameters, and some organ architecture of experimental albino rats intoxicated with carbon tetrachloride. The crude methanol extract was re-dissolved in 300 mL of distilled water and repeatedly partitioned in a separating funnel with 400 mL of n-hexane with vigorous shaking. This process was repeated using other solvents (ethyl acetate, n-butanol, and distilled water), and the n-butanol was selected based on antioxidant potency. A total of 35 albino rats were used. The rats were divided into 7 groups of 5 animals each. Lipid profile, hematological indices, and histopathological analysis were carried out. With the administration of the extract, triacylglycerol and total cholesterol levels in the Carbon tetrachloride-induced but treated rats were significantly (P<0.05) reduced compared to the normal levels, 1.84±0.27 mmol/L, and 0.54±0.11 mmol/L, respectively. In contrast, high-density lipoprotein was relatively increased compared to the normal level, 1.44±0.43 mg/dL. Similarly, packed cell volume, hemoglobin, and white blood cell levels were significantly (P<0.05) reversed to near normal in the extract-treated rats. On the other hand, the histopathological examinations of a liver section of the normal control group showed normal hepatocellular architecture with distinct hepatic cells with a well-conserved central vein. Carbo tetrachloride-induced control group liver showed intense hepatic necrosis with vascular congestion, kupffer cells hyperplasia, vacuolation, and degeneration of normal hepatic cells (hepatic necrosis). However, the induced but treated groups almost normalized the hepatic cells (moderate hepatic necrosis). The findings showed that the n-butanol fraction of F. glumosa could reverse the deleterious effects of CCl4 on lipid profile and hematological parameters with the restoration of the architectural integrities of the liver and kidney of the treated rats.

Potential Anti-carcinogenic Effect of Acetazolamide, a Carbonic Anhydrase Enzyme Inhibitor, in Diethylnitrosamine - Induced Hepatocarcinogenesis in Rats

Abstract Background Despite the progress achieved in early detection and treatment of HCC, it still accounts for a significant number of cancer-related deaths worldwide. Tumoral microenvironment acidity plays a pivotal role in tumoral cell survival, tumoral progression and metastasis. CA-IX and XII are two of several mechanisms by which tumor maintain optimal intracellular pH at the expense of the extracellular environment that turns into acidic pH. ACT is a CA inhibitor that is used in many medical indications. It is effective, safe and inexpensive. It has some side effects and it may be even contraindicated in some cases. Aim of the work To evaluate the possible anticarcinogenic role of ACT in DEN-induced HCC animal model. Materials and Methods This study showed that using DEN for 10 weeks caused significant increase in the levels of AST, ALT, total bilirubin, direct bilirubin and AFP and significant decrease in albumin level in DEN-induced HCC rat groups when compared to normal control rats. Administration of ACT for 3 weeks in ACT-treated DEN-induced HCC group caused marked improvement in the mentioned biochemical measurements (AST, ALT, total bilirubin, direct bilirubin and AFP) when compared to DEN-induced HCC rat group without ACT treatment, yet still higher than the lab values of normal control group. Results The present study demonstrated that using DEN in rat groups had induced polyhedral to round hepatocytes with dense, centrally located vesicular nuclei. The neoplastic areas showed poorly differentiated large cells with hyperchromatic nuclei and prominent nucleoli. The neoplastic cells showed anisokaryosis, anisocytosis, and deeply basophilic scanty cytoplasm and frequent mitotic figures mostly Grade III. The hepatic lobule displayed disorganization of hepatic cords with hyperplasia of Kupffer cells, multinucleated tumor giant cells with prominent basophilic nuclei and basophilic spindle cells. Conclusion Acetazolamide showed significant antitumor effect in DEN-induced HCC in rats, making it a promising agent to use against HCC either individually or in combination with any other therapeutic modalities. Further researches should be conducted in this anti HCC aspect.

Long Term Effects of Streptozotocin Induced Diabetes Mellitus on Hepatic, Nephrotic and Cardiac Physiology of Female Wistar Rats

Background: Diabetes mellitus is a metabolic disorder which leads to complications that affect the heart, kidney, liver and other vital organs. Most reports on diabetes have focused on diabetes induction using male rat models in short term studies.Objective: Here, we described the induction of diabetes in female rat and the complications of diabetes following long term hyperglycemia in female Wistar rats.Method: Rats were assigned into two groups: control (n=10) and diabetic (n=10). The latter was administered a single (50mg/Kg body weight) intraperitoneal injection of streptozotocin. Bodyweight and blood glucose were assessed for 14 weeks, after which the animals were sacrificed and biochemical and morphology parameters of the liver, kidney and heart were determined.Results: Diabetic rats showed continuous emaciation post STZ induction. The glycated haemoglobin, protein level, lipid profile, liver and kidney function markers were significantly different (p<0.05) from the control. Catalase, superoxide dismutase and glutathione-s-transferase activities were also significantly reduced in the heart, liver and kidney, and a concomitant increase in malondialdehyde concentration was observed. Focal tubular necrosis, pulmonary congestion and mild hyperplasia of kupffer cells were observed in the tissues and all tissues showed negative CD79a expression.Conclusion: This study provides data that could be useful for modelling long-term diabetes mellitus studies in female experimental rat models.