Histological Examination Of Liver Research Articles

A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis.

A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.

Indole-3-carboxaldehyde alleviates acetaminophen-induced liver injury via inhibition of oxidative stress and apoptosis

Drug-induced liver injury (DILI) occurs frequently and can be life-threatening. Increasing researches suggest that acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury. Indole-3-carboxaldehyde (I3A) alleviates hepatic inflammation, fibrosis and atherosclerosis, suggesting a potential role in different disease development. However, the question of whether and how I3A protects against acetaminophen-induced liver injury remains unanswered. In this study, we demonstrated that I3A treatment effectively mitigates acetaminophen-induced liver injury. Serum alanine/aspartate aminotransferases (ALT/AST), liver malondialdehyde (MDA) activity, liver glutathione (GSH), and superoxide dismutase (SOD) levels confirmed the protective effect of I3A against APAP-induced liver injury. Liver histological examination provided further evidence of I3A-induced protection. Mechanistically, I3A reduced the expression of apoptosis-related factors and oxidative stress, alleviating disease symptoms. Finally, I3A treatment improved survival in mice receiving a lethal dose of APAP. In conclusion, our study demonstrates that I3A modulates hepatotoxicity and can be used as a potential therapeutic agent for DILI.

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1β, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

High methionine diet mediated oxidative stress and proteasome impairment causes toxicity in liver

Methionine (Met) rich diet inducing oxidative stress is reported to alter many organs. Proteasome as a regulator of oxidative stress can be targeted. This study was performed to investigate if excessive methionine supplementation causes hepatotoxicity related to proteasome dysfunction under endogenous oxidative stress in rats. Male Wistar albino rats (n = 16) were divided into controls and treated groups. The treated rats (n = 08) received orally l-methionine (1 g/kg/day) for 21 days. Total homocysteine (tHcy), total oxidant status (TOS), total antioxidant status (TAS), hepatic enzymes levels: aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), with total bilirubin (TBil), albumin (Alb), and C-reactive protein (CRP) were determined in plasma by biochemical assays. Liver supernatants were used for malondialdehyde (MDA), protein carbonyls (PC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), 20S proteasome activities and their subunits expression, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) evaluation by appropriate methods and light microscopy for liver histological examination. Methionine treatment increased homocysteine, TOS, oxidative stress index (OSI), MDA and PC but decreased TAS, GSH, CAT, SOD, GPx with the 20S proteasome activities and their β subunits expression. Liver proteins: AST, ALT, LDH, ALP, TBil and CRP were increased but Alb was decreased. Liver histology was also altered. An increase in liver TNF-α and IL-6 levels were observed. These findings indicated that methionine supplementation associated oxidative stress and proteasome dysfunction, caused hepatotoxicity and inflammation in rat. Further investigations should be to better understand the relation between methionine, oxidative stress, proteasome, and liver injuries.

In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract

Abstract Dysphania ambrosioides (L.) holds a prominent place in Moroccan folk medicine due to its therapeutic attributes. Despite its widespread use, instances of inadvertent intoxication linked to its consumption have been reported. This study aims to evaluate the potential cytogenotoxic effects of D. ambrosioides leaf aqueous extract (DAAE) and explore the prospective protective role of vitamin C (l-ascorbic acid) through the micronucleus test conducted on (1) Vicia faba root-tip meristem and (2) mouse bone marrow cells. In addition, antioxidant enzyme activities, specifically superoxide dismutase (SOD) and catalase (CAT), were evaluated in V. faba treated with DAAE. After a 7-day daily administration of DAAE to mice, serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, and uric acid) were measured, and histological examination of liver and kidney tissues was performed. The results indicated that DAAE had dose-dependent cytotoxic and genotoxic effects on both biological models. Furthermore, V. faba treated with DAAE showed significant increases in the activities of SOD and CAT enzymes. Mice treated with DAAE exhibited significant elevations in serum biochemical parameters compared to the control group. Histological examination of liver and kidney tissues revealed hepatic degeneration, glomerular shrinkage, and distinct vacuolated tubular epithelial cells. The cotreatment with vitamin C demonstrated a significant protective effect against DAAE-induced cytogenotoxicity. These findings underscore the importance of vitamin C as a protective agent against oxidative stress and cytogenotoxicity induced by DAAE and recommend its use in any DAAE-based preparation.

Hepatoprotective effect of Indonesian propolis from Apis mellifera in carbon tetrachloride (CCl4) induced liver injury in mice

Abstract Propolis has been reported to have a broad spectrum of biological activities. The objective of this study was to investigate the hepatoprotective effect of propolis on liver injury induced by carbon tetrachloride (CCl4). Twenty-five adult mice were randomly divided into five groups of five. The normal group received distilled water; positive control group was given CCl4 at 2.8 mL/kg BW orally, other groups were given the same dose of CCl4, followed by oral propolis at 25, 50, and 100 mg/kg BW, respectively, for 14 days. On the 15th day, the mice were sacrificed for the measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, and albumin, as well as examination of liver histology. The data were analyzed using a one-way ANOVA and, subsequently, by Duncan’s Multiple Range Test. The results demonstrated that propolis had a hepatoprotective effect as shown by significant improvement of the biochemical parameters (p <0.05), which was confirmed by the liver histological analytical results. The most potent hepatoprotective effect was found after the dose of 100 mg/kg BW.

Fungi, including Pithomyces chartarum cause facial eczema and inflammation in grazing sheep in Western China

Facial eczema is often found in flocks of grazing sheep in China. To investigate fungi species those cause disease and pathological roles. Forage and soil samples were collected during the pathogenic season and cultured. Samples were collected from regions with and without facial eczema affected sheep. Fungal isolation and identification, statistical analysis of fungal species and distribution were performed. Pathological changes, biochemical parameters of serum liver function and protection of inflammatory factors that tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12) were observed. Fungal cultivation and identification showed that separation rate of Alternaria, Pithomyces chartarum, Fusarium and Aspergillus were higher, particularly, Pithomyces chartarum was significantly identical. Pathological anatomy and histology indicated that the disease likely attacked merino ewes with the age of 6 months old. The clinical manifestations were characterized by inflammational edema in face (ears and eyelids) and mandibular area. Postmortem examination of dead lambs showed enlargement of liver with yellow white patchs of necrotic lesion and tuberous sclerosis and fibrosis on section. Histologic examination of liver showed extravasated blood, severe lesion of liver cells and bile duct, and fatty degeneration. In sheep, fungal toxin induced the secretion of TNF-α, IL-6 and IL-12. These results revealed that Pithomyces chartarum maybe caused facial eczema and inflammation in sheep. The facial eczema was allergic eczema caused by hepatic dysfunction and hepatonecrosis.

Effect of different levels of Moringa oleifera seed powder to the diet on some immunological and histological parameters of common carp fish Cyprinus carpio L.

75 common carp fish with an average weight of 65.08±0.42 g were used. The fish were fed on experimental diets, which were divided into five equal treatments in terms of protein percentages, different in the proportions of adding Moringa seed powder, was 0, 0.5, 1, 1.5 and 2%, respectively; the fish were fed on the experimental diets at 5% of the live weight, divided into 4 meals a day. The liver histological examinations in T2 and T3-treated fish showed a significant improvement in the histological characteristics of hepatocytes and the contents of the liver tissue parenchyma. At the same time, it was observed that the liver tissue was slightly affected in the fish of the fourth and fifth treatments without affecting the health status of the fish. Histological examinations also showed the improvement and superiority of T2, T3, T4 and T5 treatment fish compared to control treatment fish on histological parameters of small intestine and gill tissue. This indicates that adding Moringa seed powder to fish diets at low rates stimulated the immune system and raised the concentration of IgM and IgG immunoglobulins to improve the fish's tissue health status. Keywords: Moringa oleifera, immunological, histological, common carp fish Cyprinus carpio L.

Phytochemical Screening and Toxicity Study of Methanol Stem Bark Extract of <i>Prosopis africana<i> (African Mesquite) In Albino Wistar Rat

Prosopis africana (Guill. & Perr.) is a perennial leguminous tree of the subfamily Mimosaidae and is found to grow in the savanna region of Senegal and Nigeria. Several parts of the plant has been documented to possess ethno medicinal value. The study aimed to determine the phytochemical constituents using methods described by Trease & Evans and toxicity profile (using established toxicity determination protocols) of methanol stem bark extract of Prosopis africana in albino Wistar rats. Phytochemical screening of the extract revealed the presence of alkaloids, glycosides, saponins, carbohydrates, terpenoids, flavonoids, and tannins. Acute toxicity test showed that the LD50 of the extract was 3807.88 mg/kg, with only the animal administered with 5000 mg/kg of the extract dying in phase two. The extract did not affect food and water consumption or most hematological parameters, except for red and white blood cell counts. Histological examination of liver, kidney, and heart did not show any signs of malformation. These findings suggest that the methanol stem bark extract of Prosopis africana may be safe for use in traditional medicine and could provide a basis for the development of novel drugs for the treatment of various diseases such as malaria fever, wound care and diabetes mellitus.

Novel triazole derivatives as potential rodenticides against the Norway rat, R. norvegicus: histology, biochemical alternations, and field application

Economically speaking, rodents possess a serious threat to the agriculture sector. One of these organisms that directly threaten agriculture, stocks, and others is the Norway rat, Rattus norvegicus (R. norvegicus). The 2-cyano-N-(1H-1,2,4-triazol-3-yl) acetamide (1) was used as a precursor to give 2-cyano-3-(dimethylamino)-N-(1H-1,2,4-triazol-3-yl) acrylamide (2) and ethyl 2-amino-5-cyano-1,6-dihydro-6-oxo-1-(1H-1,2,4-triazol-3-yl) pyridine-3-carboxylate (3). Infra-red, 1H-NMR, 13C-NMR, MS, and elemental analysis were done for the precise structure elucidation of the applied synthons. The prepared compounds were tested as potential rodenticides against the Norway rat, Rattus norvegicus. Toxicity analysis using four serial doses of both prepared compounds revealed that the LD50 values were 160.6 and 391.7 mg/kg body weight, for ethyl 2-amino-5-cyano-1,6-dihydro-6-oxo-1-(1H-1,2,4-triazol-3-yl) pyridine-3-carboxylate (3) and 2-cyano-N-(1H-1,2,4-triazol-3-yl) acetamide (1), respectively. Several biological variables, such as alanine transaminase (ALT), aspartate transaminase (AST), serum urea, creatinine, and total protein, have been assessed and evaluated as biological response indicators. Analysis revealed a highly significant increase in both AST, ALT, urea, and creatinine levels, while the total protein level showed a considerable reduction in treated rats exposed to 2-cyano-N-(1H-1,2,4-triazol-3-yl) acetamide (1) and ethyl 2-amino-5-cyano-1,6-dihydro-6-oxo-1-(1H-1,2,4-triazol-3-yl) pyridine-3-carboxylate (3) when compared to the control treatment. Liver histological examination showed structural changes in the form of congestion in the central vein, necrosis in some hepatic regions, and pyknotic nuclei, while kidney histological examination showed vacuolar degeneration of the epithelial cells of some convoluted tubules and the disappearance of some glomeruli and other marked atrophies. Necrosis in some areas was noticed. Field application through bait consumption took place with a satisfactory reduction of 68.4% for ethyl 2-amino-5-cyano-1,6-dihydro-6-oxo-1-(1H-1,2,4-triazol-3-yl) pyridine-3-carboxylate (3), while it was 61.9% for 2-cyano-N-(1H-1,2,4-triazol-3-yl) acetamide (1) when compared to the recommended Zinc phosphide commercial rodenticide that poses an 81% reduction.Graphic abstract

Kaempferitrin, a major compound from ethanol extract of Chenopodium ambrosioides, exerts antitumour and hepatoprotective effects in the mice model of human liver cancer xenografts.

This study aimed to investigate antitumour effect and possible toxicity of kaempferitrin, the major compound from ethanol extract of Chenopodium ambrosioides, in the mice model of human liver cancer xenografts. Forty mice bearing SMMC-7721 cells xenografts were divided into control group (not treated) and three groups orally administered with ethanol extract of C. ambrosioides, kaempferol (positive control) and kaempferitrin for 30 days. Antitumour effect was evaluated by measurement of tumour growth, histological examinations of tumours, flow cytometry detection of splenic CD19+ B lymphocytes and CD161+ Natural Killer cells, biochemical measurements of serum levels of tumour necrosis factor-α, interleukin-6, interferon-γ, malonaldehyde, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenz thiazoline-6-sulphonate) radicals. Toxicity was evaluated by histological examinations of livers and measurements of serum levels of aspartate transaminase, alanine transaminase, total bilirubin, direct bilirubin, malonaldehyde and hepatic malonaldehyde level. Kaempferitrin significantly (P < 0.05) decreased tumour volume, mass and cell number. Antitumour effect was due to induction of tumour cells necrosis and apoptosis, stimulation of splenic B lymphocytes, decreases of radicals and malonaldehyde. Kaempferitrin did not change liver structure, and decreased serum levels of transaminases, bilirubin, malonaldehyde and hepatic malonaldehyde level. Kaempferitrin exerts antitumour and hepatoprotective effects.

Antidiabetic Effect of Noni Fruit and Moringa Leaves Extract on Blood Glucose Level, Hepatic and Pancreatic Histological Features of Diabetic Mice

One of the chronic diseases with high blood glucose levels is a characteristic of Diabetes Mellitus. Utilization of herbal ingredients needs to be developed to reduce blood sugar levels in diabetes, and one of them is by using moringa leaf extract and noni fruit. This study aimed to analyze the effect of a combination of moringa leaf extract and noni fruit on blood glucose levels and tissue cytology in diabetic mice. The study was a randomized pretest-posttest control group design using 28 male mice divided into seven groups. The data analysis showed the lowest decrease in blood glucose levels in the group of diabetic mice given noni fruit and moringa leaf extract at a dose of 150mg/20g BW/oral/day for two weeks. The results of histological examination of liver and pancreas tissue showed no tissue is damaged.

Significance of histological assessment in drug-induced liver injury

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.

The effect of a drug Cisplatin and Thymoquinone material in the liver of rats after the induced of cancer in laboratary

Cisplatin drug is one of platinum compounds and it is in common use world wide for the treatment of a variety of human neoplasms. However in high doses it can produceundesirable toxic side effects on liver, so in this study we investigated whether Thymoqunion has protective effect on hepatotoxicity induced by cisplatin or not. Four equal-sized groups(four rats each) of adult female rats with colon cancer induced in two group unless control group by used azoxymethane carcinogen were used as (control group, AOM group cisplatin group, Thymoqunion group (TQ)). It was detected for tumor by measuring the concentration CEA in serum, it was observed significant increase (P&lt;0.05) when injected article carcinogen totals compared with the control group. when the transaction ad these two articles focusing decreased response to treatment user. Histological examination of livers were carried out using light microscopy. Results showed that cisplatin produced histopathological changes in liver tissue, congestion and expansion of central veins, dilatation and congestion of sinusoids, with necrosis of liver cells and endothelial cells, severe fatty infiltration and necrotic foci in large areas from liver cells, congestion of sinusoids, while Thymoqunion not appear any side effect on liver tissue

Hepatoprotective potential of Tamarindus indica following prenatal aluminum exposure in Wistar rat pups.

Over time, the use of plant-derived agents in the management of various human health conditions has gained a lot of attention. The study assessed the hepatoprotective potential of ethyl acetate fraction Tamarindus indica leaves (EFTI) during prenatal aluminum chloride exposure. Pregnant rats were divided into 5 groups (n=4); Group I rats were administered 2mlkg-1 of distilled water (negative control), Group II rats received only 200mgkg-1 aluminum chloride (positive control), Group III rats were administered 200mgkg-1 aluminum chloride and 400mgkg-1 EFTI, Group IV rats were administered 200mgkg-1 aluminum chloride and 800mgkg-1 EFTI, Group V rats were administered 200mgkg-1 aluminum chloride and 300mgkg-1 Vit E (comparative control). On postnatal day 1, the pups were euthanized, and liver tissues were harvested for the biochemical study (tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases) and the liver histological examination. The administration of EFTI was marked with significant improvement in the tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases. There was a marked improvement in histopathological changes associated with prenatal aluminum chloride exposure. In conclusion, the administration of EFTI was protective during prenatal aluminum chloride exposure of the liver in Wistar rats, and is mediated by the anti-lipid peroxidative, antiapoptotic, and anti-inflammatory activity of EFTI.

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 &amp; 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.

Therapeutic Effects of Pomegranate (Punica granatum L.) Juice on Liver of Diabetic Mice

Diabetes Mellitus (DM) is a serious metabolic disorder. Pomegranate has various biological effects. The present study evaluated pomegranate juice (PJ) therapeutic effects on the liver of Streptozotocin (STZ) induced DM mice model. Fifty male mice were distributed into 5 equal groups (10 each). Groups were negative control, PJ group received orally PJ (180 mg/kg), diabetic group received STZ (60 mg/kg), the diabetic received pomegranate juice (STZ+PJ) group, the diabetic received metformin (250 mg/kg) (STZ+MET) group. The experiment duration was 6 weeks. Initial and final body weights and liver weights were measured. At the experimental end, blood glucose levels and liver enzymes serum levels as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. A liver histological examination was made under a light microscope. STZ led to a significant decreased in final body weight, and an increase in blood glucose and serum levels of AST, ALT, and ALP versus control. PJ administration to diabetic mice significantly decreased blood glucose and serum levels of liver enzymes versus the STZ group but AST and ALP levels were still elevated versus control. Histopathological liver examination of PJ-and MET-treated groups showed amelioration of histological changes of DM. Metformin repairs damaged hepatic cells but was not as effective as PJ. In conclusion, pomegranate juice improves liver health in diabetic mice.

TOXICO-PATHOLOGICAL ASSESSEMENT OF Nerium oleander ROOTS AND LEAVES ON WISTAR RAT

The aim of the study was to evaluate the toxic effects of Nerium oleander roots (R) and leaves (L) aqueous extract on Wistar rat. Serum chemistry, epididymal sperm parameters and histological examination of liver, kidney and brain were assessed after twelve consecutive day’s oral administration of N. oleander. The extracts of R1, R2, L1 and L2 induced no treatment-related adverse effects with regard to general behaviors, hematological, serum chemistry, epididymal sperm parameters and histological profiles of liver, kidney and brain. However, the higher doses (R3, L3) led to, diarrhea, weakness, anorexia, frequent urination, and nasal hemorrhage, with no mortality. The hematological data revealed a significant increase in the levels of hematocrit and platelets in both L3 and R3 compared to the control. However, these two extracts have not affected the level of RBC, hemoglobin, WBC, and lymphocytes, while the L3 has reduced the concentration of glucose and increased that of urea. However, triglycerides, total cholesterol, alanine aminotransferease, albumin, conjugated bilirubin, potassium and calcium levels of L3 and R3 were not statistically significant compared to the control. Simultaneously bilirubin concentration was increased significantly in L3 and R3. There were no significant differences in epididymal sperm analysis when compared to the control. Adverse histological changes were observed in both liver and kidney as well as in the brain. To conclude, N. oleander extracts have disturbed the levels of certain vital variables in rats at higher dose, in which caution should be taken during the use of this plant.

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent.

The present study is based on screening new and potent synthetic heterocyclic compounds as anti-diabetic drugs using various computational tools, lab experiments, and animal models. A potent synthetic compound 2-(3-benzoyl-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-1-(2-bromophenyl) acetamide (FA2) was checked against diabetes and screened via enzyme inhibition assays, enzyme kinetics against alpha-glucosidase and alpha-amylase. Protein-ligand interaction was analyzed via molecular docking and toxicological analysis via ADMET. Experimental animals were used to examine the compound FA2 safety, delivery, and check various biochemical tests related to diabetes like fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin level. Histography of liver, kidney, and pancreas was also performed. Results showed that FA2 had binding energy of -7.02 Kcal/mol and -6.6 kcal/mol against α-glucosidase (PDB ID: 2ZE0) and α-amylase (PDB ID: 1B2Y), respectively. Moreover, in vitro enzyme inhibition assays and enzyme kinetics against α-glucosidase and α-amylase were performed, and FA2 showed IC50 at 5.17 ± 0.28 µM and 18.82 ± 0.89 µM concentrations against α-glucosidase and α-amylase, respectively. Kinetics studies showed that the FA2 compound impeded α-glucosidase and α-amylase as a non-competitive mode of inhibition with Ki' values -0.320 ± 0.001 and 0.141 ± 0.01, respectively. FA2 was further analyzed on alloxan-induced mice for 21 days. Biochemical tests (fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin levels) and histological examination of liver and kidney showed that the FA2 compound showed better results than acarbose. Histology of pancreas found to show the maintenance of normal pancreatic acini and Langerhans islets in FA2 treated mice compared to acarbose and nontreated diabetic controls. Investigating anti-diabetic potential of FA2 compound showed that the selected benzothiazine derivative has tremendous importance in reducing dose concentration and side effects.

A Meta-Analysis of How Nonalcoholic Fatty Liver Disease Affect Antiviral Treatment of Patients with e Antigen-Positive Chronic Hepatitis B.

Background Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are both the most common underlying diseases leading to cirrhosis and hepatocellular carcinoma, and NAFLD and HBV infection are the first and second leading causes of chronic liver disease in China. However, there are still a lot of controversies about whether the combined presence of CHB and NAFLD will affect the course or outcome of liver disease together with HBV, and how the two affect each other. Objective To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on antiviral therapy in patients with chronic hepatitis B (CHB). Methods Computer searches of databases such as PubMed, CNKI, VIP.com, and Wanfang Data Knowledge Service Platform were used. The time frame was from the creation of the database to June 2022. The search subject terms were hepatitis B, CHB, or NAFLD. The observation group consisted of patients with e antigen-positive CHB with NAFLD, and the control group consisted of patients with e-antigen + CHB. Extracts including title, name, date of publication, number of samples, antiviral drugs, and outcome indicators were used for Meta-analysis. Funnel plots were drawn to analyze literature bias. Results Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results. Meta-analysis showed that CHB patients with NAFLD had lower efficacy than CHB patients after 48 weeks of antiviral treatment with nucleotide analogs, as measured by three outcome indicators HBV DNA conversion rate, ALT-normalization, and HBeAg conversion rate. Conclusion NAFLD reduces the effect of antiviral therapy in CHB patients, and the clinicopathological features of patients with NAFLD combined with chronic hepatitis B are different from those of patients with chronic hepatitis B alone, so early diagnosis by liver histological examination should be actively performed and reasonable antiviral therapy should be administered.