Histopathological Examination Of Liver Research Articles

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Combined exposure of polystyrene microplastics and benzo[a]pyrene in rat: Study of the oxidative stress effects in the liver

Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5μm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.

H Hepatoprotective Activity of Piper crocatum (Ruiz &amp;Pav.) Leaves Against Monosodium Glutamate -Induced Hepatotoxicity in Rats

Monosodium glutamate (MSG) is widely used as additive in food. Excess consumption of MSG was reported to cause oxidative stress on liver resulted increased production of reactive oxygen species (ROS). Without proper treatment, it can induce liver injury and fatal hepatic diseases, including cirrhosis. Red betel (Piper crocatum Ruis and Pav.) is one of Indonesia’s medicinal plants that has been known to exhibit antioxidant activity. The current study evaluated hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury.  Animals (n=5 per group) were randomly divided into five groups as follows: Group 1, control (distilled water); group 2, negative control, receive 7 mg/kg bw of MSG; group 3, receive oral 7g/kg b.w of MSG plus 200 mg/kg bw RBLE; group 4, receive oral 7g/kg b.w of MSG plus 400 mg/kg b.w RBLE and group 5, receive oral 7g/kg b.w of MSG plus 600 mg/kg b.w RBLE. The rats were sacrificed on twenty-ninth day of the experiment. Measuring serum levels of aspartate aminotransferase (AST) and alanin aminotransferase (ALT) was done. Histopathological examination of liver was performed by calculated necrosis cell percentage.  RBLE treatment (200 mg/kg b.w) decrease alanin aminotransferase and aspartate aminotransferase demonstrated increased compare to negative control. The histological findings revealed RBLE treatment were also able to decrease necrosis cells percentage. The study was able to demonstrate that RBLE treatment could decrease necrotic cell percentage. Low concentration of RBLE (200 mg/kg b.w) exhibit best anti-inflammatory properties and had the lowest ALT enzyme and increased live cell percentage by shifting cell death pathway from necrosis to apoptosis, and these indicating its antioxidant properties.  These results could be used as a baseline in the purification of red betel bioactive components to be used for liver injury medication.&#x0D; Key words: Antioxidant, hepatoprotective, histopathology, liver enzymes, MSG, red betel.

Mulberry and Hippophae‐based solid beverage attenuate hyperlipidemia and hepatic steatosis via adipose tissue–liver axis

AbstractDyslipidemia and hepatic steatosis are the characteristics of the initial stage of nonalcohol fatty liver disease (NAFLD), which can be reversed by lifestyle intervention, including dietary supplementation. However, such commercial dietary supplements with solid scientific evidence and in particular clear mechanistic elucidation are scarce. Here, the health benefits of MHP, a commercial mulberry and Hippophae‐based solid beverage, were evaluated in NAFLD rat model and the underlying molecular mechanisms were investigated. Histopathologic examination of liver and white adipose tissue found that MHP supplementation reduced hepatic lipid accumulation and adipocyte hypertrophy. Serum biochemical results confirmed that MHP effectively ameliorated dyslipidemia and decreased circulation‐free fatty acid level. RNA‐Seq‐based transcriptomic analysis showed that MHP‐regulated genes are involved in the inhibition of lipolysis of adipose tissue and thus may contribute to the reduction of hepatic ectopic lipid deposition. Furthermore, MHP upregulated ACSL1–CPT1a–CPT2 pathway, a canonical pathway that regulated mitochondrial fatty acid metabolism, and promoted liver and adipose tissue fatty acid β‐oxidation. These results suggest that adipose tissue–liver crosstalk may play a key role in maintaining glucose and lipid metabolic hemostasis. In addition, MHP can also ameliorate chronic inflammation through regulating the secretion of adipokines. Our study demonstrates that MHP is able to improve dyslipidemia and hepatic steatosis through crosstalk between adipose tissue and liver and also presents transcriptomic evidence to support the underlying mechanisms of action, providing solid evidence for its health claims.

Profiling of two Lampranthus species using LC-ESI/MS with evidence of their hepatoprotective activity

Lampranthus glaucus and Lampranthus glaucoides are only reported to have significant cytotoxic activity against certain cancer cell lines with phytochemical investigation of their petroleum ether and the ethyl acetate extracts. Further investigation was suggested concerning their hepatoprotective activity and relating it to the metabolic profile of their defatted methanol extracts using LC–ESI/MS analysis. Hepatoprotective activity was evaluated through assessment of three liver parameters as well as liver histopathological examination in thioacetamide-induced hepatotoxicity model. Sixty-eight and 26 phytochemicals were tentatively identified in L. glaucoides and L. glaucus, respectively, with phenolic compounds as the major class. Both plants showed significant inhibition of serum GPT and GOT levels, inhibition of tissue IL-1β and TNF-α levels and inhibition of tissue NF-κβ and caspase-3 gene expression proving hepatoprotective action. Liver treated with L. glaucoides showed lesion scoring range between negative to mild, whereas L. glaucus showed a range between mild to moderate.

Combined metabolomic and proteomic analysis of sepsis related acute liver injury and its pathogenesis research

BackgroundSepsis-induced acute liver injury is common in patients in intensive care units. However, the exact mechanism of this condition remains unclear. The purpose of this study was to investigate the roles and mechanisms of proteins and metabolites in the liver tissue of mice after sepsis and elucidate the molecular biological mechanisms of sepsis-related liver injury. MethodsFirst, a lipopolysaccharide (LPS)-induced sepsis mouse model was established. Then, according to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection in mouse serum and liver histopathological examination (HE) staining, the septic mice were divided into two groups: acute liver injury after sepsis and nonacute liver injury after sepsis. Metabolomics and proteomic analyses were performed on the liver tissues of the two groups of mice to identify significantly different metabolites and proteins. The metabolomics and proteomics results were further analysed to identify the biological indicators and pathogenesis related to the occurrence and development of sepsis-related acute liver injury at the protein and metabolite levels. ResultsA total of 14 differentially expressed proteins and 46 differentially expressed metabolites were identified. Recombinant Erythrocyte Membrane Protein Band 4.2 (Epb42) and adenosine diphosphate (ADP) may be the key proteins and metabolites responsible for sepsis-related acute liver injury, according to the correlation analysis of proteomics and metabolomics. The expression of the differential protein Epb42 was further verified by western blot (WB) detection. ConclusionsOur study suggests that the differential protein Epb42 may be key proteins causing sepsis-associated acute liver injury, providing new and valuable information on the possible mechanism of sepsis-associated acute liver injury.

Effect of Guduchi Triphala Kwatha with Lohabhasma as Prakshepa Churna in the Management of Obesity

Obesity a complex metabolic disorder, involves the excessive accumulation of adipose tissue and it is recognised as a major global health challenge. Preclinical study conducted on obesity provides valuable insights into the revalidation of the treatment approach of Sthoulya. Methods: In this study the efficacy of Guduchi Triphala Kwatha added with Lohabhasma, as Prakshepa Churna evaluated in High fat diet (HFD) fed, obese Wistar albino rats. A Control group containing 6 rats were administered with distilled water (9.86ml/kg), another group received standard drug Orlistat (30mg/kg) and the trial group was given Kwatha (9.86ml/kg) added with Lohabhasma (25.65mg/kg). High fat diet was continued throughout the study period. All the drugs were administered orally once a day for 30 days. At the end of the experimental period various physical, biochemical and histopathological observations were made. Results: Data of in-vivo studies revealed that significant reduction in body weight, body mass index (BMI), waist circumference (WC), upon trial drug treatment. Elevated levels of, insulin, leptin, lipid profile, liver function, kidney function and antioxidant status were also showed significant results. Milder changes were observed in histopathological examination of Liver, Kidney and Adipose tissue even though HFD was continuing throughout the study period. Conclusion: The trial drug showed significant result in the assessment parameters after treatment.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination

BackgroundMultiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin.MethodsMale Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out.ResultsThe results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys.ConclusionIn summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.

Exploring Acute and Sub-Acute Toxicity of Gramine Bioactive Molecule in Wistar Rats.

ABSTRACT: The study evaluated the toxicity of Gramine in Wistar rats using a specified dose for acute and subacute toxicity evaluation. Female rats were given the Single dose as specified in OECD Guideline 425. Subacute toxicity was assessed using doses of 13, 27.5, and 55 mg/kg p.o. compared to a control group. After treatment, the satellite group continued operating for 14 days to assess the recovery effects. No mortality was observed at doses of 175mg/kg, but mortality was observed at doses of 550 mg/kg. In a subacute toxicity investigation, rats given Gramine orally for 28 days showed significant weight loss, reduced food intake, and normal water consumption. No harmful effects were observed for haematological or biochemical parameters, and no evidence of deterioration was found in brain, kidney, or liver histopathological examinations. The results indicate that 13, 27.5, and 55 mg/kg were considered safe doses for both short- and long-term oral therapy.

Identification and characterisation of emerging fish pathogens Aeromonas veronii and Aeromonas hydrophila isolated from naturally infected Channa punctata.

Naturally infected Channa punctata exhibiting bacterial septicemic syndrome including ulcerations along with mortality records were collected from a fish farm in Assam during winter season (early November 2020 to early January 2021). The moribund fishes were subjected for bacterial isolation followed by identification of the bacteria. Two dominant emerging bacterial pathogens were identified as Aeromonas veronii (isolate ZooGURD-01) and Aeromonas hydrophila (isolate ZooGURD-05) by standard biochemical characterization and 16S rRNA and rpo B gene amplification. Re-infection experiments of both the bacterial isolates in healthy disease-free C. punctata showed similar symptoms to that of natural infection thus confirming their virulence. The LD50 calculated during challenge test for both the isolates ZooGURD-01 and ZooGURD-05 found to be pathogenic at 2.6 × 104 and 1.6 × 104CFU/fish respectively. Further PCR amplification of specific virulent genes (aerolysin, hemolysin and enterotoxin) confirmed pathogenicity for both isolates. Histopathological examinations of liver and kidney in re-infection experiments showed prominent changes supporting bacterial septicaemia. Antibiotic sensitivity pattern showed that the isolates ZooGURD-01 and ZooGURD-05 were sensitive to 22 and 19 out of 25 antimicrobials respectively. The present study was the first report on the mortality of farmed C. punctata associated with natural infection caused by A. veronii and A. hydrophila with no record of pathogenicity of A. veronii in C. punctata.

Evaluation of the Acute Toxicity of Acetaminophen in Mice

Acetaminophen (N-acetyl-para-aminophenol, APAP), widely used for pain relief across specie, poses significant toxicity risks. This study ‎aimed to assess the acute toxicity profile of APAP by determining the median toxic dose ‎‎(TD50) in a ‎‎murine model. Sixty male Balb/c mice, aged 8 weeks and weighing 20-30 ‎g, were randomized into six equal groups. Five groups received single oral doses of APAP (150, 200, 300, 500, and 700 mg/kg BW), while the control group received distilled water. The TD50 was ‎computed utilizing the probit method. Animals were ‎‎monitored for 24 h for ‎any sign indicative of clinical toxicity. Post-exposure, liver and kidney necropsies were conducted for histopathological analysis. Predominant symptoms of toxicity included prostration, hematuria, heightened agitation, lacrimation, cyanosis, and recumbency across doses from 150 to 700 mg/kg BW. The TD50 for APAP was estimated to be 732 ‎mg/kg BW. The liver histopathological examination of mice treated ‎‎with 700 mg/kg BW APAP ‎revealed severe multifocal hyper eosinophilic hepatocytes, indicating areas of centrilobular ‎necrosis, disorganized ‎‎hepatic cords, and multiple hemorrhage regions. The kidney ‎examination exhibited no pathological changes in treated mice with 700 mg/kg BW ‎‎APAP. In ‎conclusion this investigation provides critical insights into the acute toxicity profile of APAP. The findings not only highlight the ‎‎potential risk associated with APAP usage but also the ‎necessity of strict monitoring for stringent dosage control. Further research is also ‎‎needed to ‎understand the underlying mechanism of APAP-induced toxicity and pave the way for the ‎development of efficacious therapeutic ‎strategies to counter APAP overdose‎‎‎‎.

Hematopoietic effect of echinochrome on phenylhydrazine-induced hemolytic anemia in rats

Background Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes’ average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate &amp; alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde &amp; nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.

Hepatoprotective potential of Phyllanthus niruri and Andrographis paniculata in isoniazid-rifampicin induced hepatotoxicity in rats

BackgroundIsoniazid (INH) and Rifampicin (RIF) are the common drugs causing hepatitis in patients undergoing Antitubercular therapy (ATT). This often results in discontinuation of the therapy or change in the treatment regimen. Free radical injury by drug metabolites has been postulated as cause of liver damage. The herbal extracts of Phyllanthus niruri and Andrographis paniculata possess antioxidant activity. MethodsHepatotoxicity was induced in Sprague Dawley rats by administering Isoniazid (100 mg/kg, po) and Rifampicin (100 mg/kg, po) combination for 14 days. Each group of rats were simultaneously treated with P. niruri (125 mg/kg, po), A. paniculata (125 mg/kg, po) and in combination of both for 14 days. Assessment of hepatotoxicity was done by evaluating serum total bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), liver superoxide dismutase (SOD), liver catalase levels, and histopathological examination of liver. ResultsThere was a significant reduction in the total bilirubin and SGOT levels in the groups treated with P.niruri, A.paniculata and combination of P.niruri and A.paniculata when compared with the INH and RMP treated groups (P<; 0.0001, P = 0.03, P < 0.0001) respectively. The liver SOD and Catalase enzymes were significantly deranged in the group treated with INH and RMP compared to the control animals (P < 0.0001). However, the SOD and Catalase levels were significantly elevated in the groups treated with these protective agents (P < 0.0001) when compared with INH and RMP group. Histopathological examination revealed that in the groups treated with INH and RMP, grades 1 & 2 necrosis was observed than those animals of the normal control group (p = 0.002). However, treatment with P.niruri and A.paniculata extracts showed no signs of necrosis on comparing with the INH and RMP group (p = 0.002). ConclusionExtracts of P. niruri and A. paniculata both in monotherapy and combination has hepatoprotective action against the hepatotoxicity induced by Isoniazid and Rifampicin.

[Acute toxicity test of the Li-Dan-He-Ji granules].

To observe the acute toxic reaction of the Li-Dan-He-Ji granules, and to evaluate its safety. Sixty C57BL6/J mice were randomly divided into normal control group, vehicle group and drug treatment group, with 10 females and 10 males in each group. According to the Technical guidelines for the study of toxicity of single drug administration, the maximum administration dosage (MAD) was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g (42.8 g/kg), three times within 24 hours, with an interval of 6 hours. The vehicle group was fed with the same pure water. The normal control group received no treatment. The mice were observed continuously for 14 days, and the appearance characteristics, behavioral activities, body weight changes and the number of deaths in each group were recorded. At the 14 days, blood samples were collected from the eyeballs, and routine blood tests such as white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), lymphocyte percentage (LYM%), neutrophil percentage (NEU%), red blood cell count (RBC), hemoglobin (Hb), and platelet count (PLT) were performed. And alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and other biochemical indicators. The mice were then sacrificed, and the histopathological changes of liver and kidney were observed by hematoxylin-eosin (HE) staining. The organ indexes of heart, liver, spleen, lung, kidney and thymus were calculated. The median lethal dose (LD50) of Li-Dan-He-Ji granules were not obtained. During the MAD experiment, the animals in each group did not die, their behavioral activities were normal, and there was no significant change in liver and kidney histopathological examination. There were no significant differences in body weight, blood routine, biochemical indexes and organ index among all groups (all P > 0.05). The body weight (g) of normal control female and male group, vehicle female and male group and drug female and male group before administration were 18.96±1.14, 19.65±1.45, 19.33±1.30, 19.53±1.22, 19.28±1.69 and 19.48±1.28; 14 days after administration were 27.69±0.81, 28.19±2.22, 27.77±1.00, 27.88±1.85, 27.92±1.33 and 28.07±1.93, respectively. The Li-Dan-He-Ji granules have low oral toxicity, combined with clinical observation, can be safely used in infants.

A UPLC-QTOF/MS-based hepatic tissue metabolomics approach deciphers the mechanism of Huachansu tablets-based intervention against hepatocellular carcinoma

Huachansu (HCS) tablets, classified as well-known traditional Chinese medicine (TCM) preparation, have been proved to be effective in the treatment of hepatocellular carcinoma (HCC) in clinical studies. However, the underlying mechanism of HCS tablets against HCC has not been comprehensively elucidated. In this study, a rat model of HCC was established with diethylnitrosamine (DEN) inducer. The efficacy of HCS tablets against HCC was assessed through liver histopathological examination and evaluation of biochemical indicators. A metabolomics method based on UPLC-Q-TOF/MS combined with multivariate data analysis was established to identify differential metabolites related to the inhibition effect of HCS tablets on HCC, and then the relevant metabolic pathway analysis was performed to investigate the anti-HCC mechanisms of HCS tablets. The results showed that compared to the control group, the HCC model group showed a significant increase in the values of HCC-related biochemical indicators and the number of tumor nodules, indicating the successful establishment of the HCC rat model. Upon treatment with HCS tablets, the values of HCC-related biochemical indicators decreased, liver fibrosis and nuclear deformation were also significantly alleviated. A total of 15 differential metabolites associated with the anti-tumor effect of HCS tablets on HCC were screened and annotated through hepatic tissue metabolomics studies. Analysis of metabolic pathways revealed that the therapeutic effects of HCS tablets on HCC mainly involved the pentose and glucuronate interconversions and arachidonic acid metabolism. Further western blotting corroborated that the alteration in arachidonic acid (AA) level after the intervention of HCS tablets was related to the inhibition of cPLA2α expression in rat liver tissues. In conclusion, HCS tablets exhibit a certain anti-tumor effect on HCC, and the metabolomics method based on UPLC-Q-TOF/MS combined with further verification at the biochemical level is a promising way to reveal its underlying mechanism.

The potential protective and therapeutic effects of cannabidiol oil on experimental Leukemia induced by DMBA in male rats.

7,12-Dimethylbenzanthracene (DMBA) is a member of the polycyclic aromatic hydrocarbon family. Itis a member of the polycyclic aromatic hydrocarbon family. It is a mutagenic, carcinogenic, and immunosuppressor agent. Cannabidiol (CBD) is a phytocannabinoid. It has anticonvulsant, anti-inflammatory, anti-anxiety, antioxidant, and anti-cancer properties.The purpose of this study was to investigate the possible protective and therapeutic benefits of CBD oil in DMBA-induced leukemia in rats. Experimental animals were divided into six groups of five rats each. Group 1 (normal control) included healthy rats. Group 2 included normal rats thatreceived olive oil. Group 3 included normal rats that received CBD. Group 4 included theDMBA-induced leukemic group. Group 5 (prophylactic group) included rats thatreceived CBD as a prophylaxis before IV injection with DMBA. Group 6 (treated group) included DMBA-induced leukemic rats that received CBD as treatment. Liver functions (total, direct and indirect bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), albumin, globulin, and albumin globulin ratio) were measured. Superoxide dismutase (SOD) and catalase (CAT) were also measured. Total RNA extraction followed by-real time qRT-PCR gene expression of LC3-II, Beclin, mTOR, and P62 was performed. Histopathological examination of liver and spleentissues was performed. Administration of CBD in groups 5 and 6 resulted in a significant improvement ofthe levels of liver functions compared to theleukemic untreated rats. Also, the levels of catalase and SOD significantly increased after treatment with CBD compared to the leukemic group. After treatment with CBDin groups 5 and 6, there were downregulations in the expression of all studied genescompared to leukemic untreated rats. Treatment with CBD was more statistically effective than prophylactic use. Administration of CBD resulted in a significant improvement in the biochemical, antioxidant status, morphological, and molecular measures in DMBA-induced leukemia in adult male rats. The therapeutic use was more effective than the prophylactic one.

In vitro and in vivo studies of a newly synthesized copper-cetyl tri-methyl ammonium bromide combined with gallium oxide nanoparticles complex as an antitumor agent against hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) is one of the most leading causes of death worldwide. Previous studies reported that gallium alone and cetyltrimethylammonium bromide (CTAB) have antineoplastic activities; therefore, this study aimed to evaluate the activity of copper-cetyl tri-methyl ammonium bromide with gallium oxide nanoparticles (Cu-CTAB+GaO-NPs) against HCC by using in vitro and in vivo studies. Methods: In vitro study was performed to evaluate the cytotoxic effects of Cu-CTAB+GaO-NPs and GaO-NPs on HepG-2 cell line using crystal violet dye assay. In vivo study was done on diethyl nitrosamine (DEN) induced HCC Wister rats. Rats were randomly divided into eight groups; control, Cu-CTAB, GaO-NPs, Cu-CTAB+GaONPs, DEN, DEN+Cu-CTAB, DEN+GaO-NPs and DEN+Cu-CTAB+GaO-NPs. Histopathological examination of liver and biochemical parameters such as liver function markers, oxidative stress-antioxidants markers, tumor makers, apoptosis makers were studied. Results: Results obtained from in vitro study revealed that Cu-CTAB+GaO-NPs and GaO-NPs affect the cell viability of HepG-2 cancer cell with IC50 0.2μg/ml and 360μg/ml, respectively. Cu-CTAB+GaO-NPs exerted an antiproliferative effect in experimental rat models of HCC, as demonstrated both histologically, since it facilitated the tissue recovery of the damaged liver, and biochemically as showed by the reduction of liver function markers (ALT & AST), oxidative stress markers (MDA) and tumor makers (AFP,TGF-β1,α-L-Fucosidase); while antioxidants markers (SOD), apoptosis markers (caspase-3 mRNA) and araginase activity were elevated in DEN+Cu-CTAB, DEN+GaO-NPs and DEN+Cu-CTAB+GaO-NPs groups when compared to DEN group. Conclusion: The present study demonstrated that both Cu-CTAB alone and/or combined with GaO-NPs exerted cytotoxic effects against DEN-induced HCC, which would in turn, speculate a possible therapeutic role of the novel Cu-CTAB+GaO-NPs compound.

Modeling and in-vivo evaluation of fibrinolytic enzyme produced by Bacillus subtilis Egy under solid state fermentation

Blood clot formation increases cases of myocardial infarction (AMI) and stroke, thus urges directing much research works for treatment and prevention of the causes. One of these directions is the microbial production of fibrinolytic enzymes as thrombolytic agents. In the current work, Bacillus subtilis Egy has been used for enzyme production under solid state fermentation. Among twelve nutrient meals in addition to wheat bran as a control fodder yeast yielded the highest enzyme activity reaching 114U/g. Applying statistical model for optimization of enzyme production revealed that 3.6%, fodder yeast; 40%, moisture content; 6 days, incubation period and 2%, inoculum size were the optimum conditions for maximum fibrinolytic enzyme production (141.02 U/g) by Bacillus subtilis Egy under solid-state fermentation The model was significant and data were experimentally validated. The produced fibrinolytic enzyme was evaluated for in vitro and in vivo cytotoxicity. In-vivo examination of the enzyme resulted in no mortality during the first 24 h after treatment. After 14 days, the results revealed no significant changes detected in hematological parameters (RBCs, MCV, hemoglobin except WBCs which showed an increase for both sexes. Histopathological examination of liver and kidney of rats received oral and subcutaneous treatments showed normal architecture. The data showed the applicability of the produced enzyme for the treatment of blood clot with no significant effect on living cells or on physiological functions.

Ameliorative effect of resveratrol against cymoxanil-mancozeb induced toxicity in rats.

This study was conducted to evaluate the cymoxanil-mancozeb (CM) toxicity and investigate the ameliorative effect of resveratrol (Res) against cymoxanil-mancozeb toxicity. Forty rats were divided into four groups; the first group was used as a control group, the second group was exposed to Res only at a dose of 20 mg/kg body weight for 4 weeks, and the third group was administered CM only at a dose of 799 mg/kg body weight for 4 weeks, The fourth group was co-treated with Res+CM for 4 weeks. Blood samples were analyzed for hematological and biochemical parameters. The comet assay was done on liver and blood specimens and histopathological examinations of the liver and intestine. The results demonstrated that CM exposure caused a significant increase in WBCs, lymphocytes, granulocytes, monocytes ALT, AST, ALP, and GGT, and total cholesterol and triglycerides levels accompanied by a decrease in HGB, HCT, RBCs and MCV, MCH, MCHC, HDL and glucose levels with no significant DNA damage in liver and blood. CM mixture induced severe pathological changes in small intestine and liver. Co-treatment of Res with CM improved hematological picture, lipid and glucose profiles also liver enzymes and decreased changes in the architecture of the liver and intestine.

Exposure to dithiocarbamate fungicide Ziram results in hepatic and renal toxicity in Long Evan rats

Ziram is a dimethyldithiocarbamate fungicide that is complexed to the metal zinc. The focus of this study is to examine the effects of dimethyldithiocarbamate exposure on metal homeostasis, glutathione levels, and the physiological parameters of the kidney and liver in Long-Evan rats. Our results indicate significant accumulation of copper or zinc, and changes in total GSH or GSH/GSSG ratio in the liver and kidneys of animals treated with Ziram only. Histopathological examination of liver and kidney sections indicate the presence of infiltrates in the liver of animals treated with Ziram only, whereas protein aggregates, sloughing of cells and increased KIM-1 positive cells, an indicator of tubule deterioration, are seen in the kidneys of animals treated with Ziram and sodium-dimethyldithiocarbamate, the salt form of the dimethyldithiocarbmate backbone. These findings suggest that the overall toxicological effect of Ziram is mediated by an intrinsic property rather than to dimethyldithiocarbamate backbone or metal moiety.