Carcinoma In Male Wistar Rats Research Articles

Effect of Rosemary Leaf Ethanol Extract (Rosmarinus officinalis L.) on Arginase-1 and Tumor Suppressor P53 Expression of Hepatocellular Carcinoma in Male Wistar Strain Rats (Rattus norvegicus L.) Induced By p-Dimethylamino benzaldehyde (DMBA)

Aims: Tumor Suppressor p53 is a frequent research target to further understand the mechanisms of cancer development and the pathogenesis of cancer. Arginase-1 may also be a potential prognosis predictor for HCC patients, and also be a new target for HCC treatment. This research aims to scientifically test whether the administration of ethanol extract from Rosemary leaves (Rosmarinus officinalis L.) inhibits the increase in Arginase-1 and inhibits the increase in Tumor Suppressor p53 from Hepatocellular Carcinoma in Rats (Rattus norvegicus L) Male Wistar induced by p -Dimethylamino Benzaldehyde (DMBA). Study Design: This study used an in vivo laboratory test method. This study employed true experimental laboratories to evaluate the effects of rosemary leaf extract. Place and Duration of Study: Department of Pharmacology and Therapy and Department of Histology, Faculty of Medicine, Udayana University, between December 2023 to July 2024. Methodology: Wistar rats were induced with p-Dimethylamino Benzaldehyde (DMBA) and treated with varying doses of ethanol extract from rosemary leaves (200 mg/kg BW, 400 mg/kg BW, and 800 mg/kg BW). A control group was included, and the experiment was replicated five times. Hepatocellular carcinoma in liver tissue samples was evaluated through immunohistochemistry for Arginase-1 and Tumor Suppressor p53 expression. Interpretation of immunoreactivity was based on Histochemical scoring (H-score) assessment. Results: The results showed that the ethanol extract of rosemary leaves inhibited the decrease in Tumor Suppressor p53 expression in the DMBA-treated group. Significant increases in p53 expression were observed at doses of 400 mg/kg and 800 mg/kg BW. One-way ANOVA of the immunohistochemical tests for Arginase-1 and p53 revealed a significant difference between groups (p < 0.05). The ethanol extract of rosemary leaves demonstrated a potential to inhibit the decrease in Tumor Suppressor p53 expression but did not significantly affect the expression of Arginase-1 in hepatocellular carcinoma in male Wistar rats induced by p-Dimethylamino Benzaldehyde (DMBA). Conclusion: Ethanol extract of rosemary leaves could not inhibit the increase in arginase-1 expression and inhibit the decrease in tumor suppressor p53 of hepatocellular carcinoma in male Wistar rats induced by p-Dimethylamino benzaldehyde (DMBA).

A Saffron based Polyherbal Formulation DuK Prevents Hepatocellular Carcinoma in Male Wistar Rats.

Duk is a well-established traditional drug which has been used since time immemorial by Indian practitioners to cure various human ailments. The purpose of this study was to explore the anti-cancer activity and the possible mechanism of Duk against diethylnitrosamine (DEN)-initiated hepatocarcinogenesis. We administered Duk at 3 doses, viz., 75, 150, and 300 mg/kg/day, 2 weeks before the DEN and continued it for 16 weeks. After 1 week of DEN recovery, 2-aminoacetylflourine (2-AAF) was administered to promote hepatocarcinogenesis. We found that Duk significantly reduced the DEN and 2-AAF induced phenotypical changes in rats and restored the activities of serum markers. Furthermore, Duk counteracted the oxidative stress induced by carcinogens as observed by restoration in the levels of superoxide dismutase (SOD) and catalase (CAT). Duk significantly diminished the levels of malondialdehyde (MDA) in a dose dependent manner and restored the liver microarchitecture as assessed by histopathological studies. The results of immunohistochemical staining showed that Duk inhibited the DEN-induced decrease in the number of cells positive for Bid and Caspase-9. It also reduces the number of cells positive for Cyclin D. Duk significantly protects rat liver from hepatocarcinogenesis by regulating oxidative damage and restoring serum markers. The chemopreventive effect of Duk might be through induction of apoptosis.

Protective effects of Althaea officinalis L. extract against N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats through antioxidative, anti-inflammatory, mitochondrial apoptosis and PI3K/Akt/mTOR signaling pathways.

Hepatocellular carcinoma is the fourth cause of death due to cancer and includes 90% of liver tumors. Therefore, in this study, it was tried to show that Althaea officinalis L. flower extract (ALOF) can protect hepatocytes against N-diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Totally, 70 Wistar rats were divided into seven groups (n = 10/group) of sham, DEN, treatment with silymarin (SIL; DEN + SIL), treatment with ALOF (DEN + 250 and 500 ALOF), and cotreatment with SIL and ALOF (DEN + SIL + 250 and 500 ALOF). At the end of the study, the serum levels of liver indices (albumin, total protein, bilirubin, C-reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL-6, IL-1β, IL-10, and TNF-α), and oxidants parameters (glutathione peroxidase [GPx], superoxide dismutase [SOD], catalase [CAT] activity along with nitric oxide [NO] levels) were evaluated. The level of Bax, Bcl-2, Caspase-3, p53, PI3K, mTOR, and AKT genes were measured. ALOF in cotreatment with SIL was able to regulate liver biochemical parameters, improve serum antioxidant indices, and decrease the level of proinflammatory cytokines significantly (p < .05). ALOF extract in both doses of 250 and 500 mg/kg in cotreatment with SIL caused a significant (p < .05) decrease in the p53-positive cells and a significant (p < .05) increase in Bcl-2-positive cells. Therefore, ALOF was able to modulate the proliferation of cancer cells and protect normal cells through the regulation of Bax/Bcl-2/p53 and PI3K/Akt/mTOR signaling pathways. It seems that ALOF can be used as a prodrug or complementary treatment in the protection of hepatocytes in induced damages caused by carcinogens.

Camel (Camelus Dromedarius) Milk Antibodies Ameliorated Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats

Hepatocellular carcinoma (HCC) is an extremely aggressive solid tumor and relates to numerous cases of cancer-associated deaths globally. Current studies reveal that natural compounds retain various therapeutic effects. This study was aimed to investigate the beneficial antitumor effects of camel (Camelus dromedarius) milk antibodies (CM-IgG) on diethylnitrosamine (DENA)-induced hepatocellular carcinoma in male Wistar rats. Hepatocarcinoma was induced in rats using DENA (50 mg/kg, twice/week) for 2 weeks followed by CCl4 (1 ml/kg, trice/week) for 6 weeks. At week 17th, HCC-bearing rats were orally administrated CM-IgG (100 mg/kg, orally) daily for 4 weeks. Liver enzyme activities and levels of alpha-fetoprotein (AFP) were measured in serum. Lipid peroxidation, nitric oxide, reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity were determined in liver homogenate. Histological analysis using hematoxylin and eosin stain was examined in liver tissues. Hepatic mRNA gene expression of placental glutathione-s-transferase (GST-P) was determined by qRT-PCR. Treatment HCC-bearing rats with CM-IgG significantly reduced liver injury biomarkers and attenuated oxidative stress as well as enhanced antioxidant status. Moreover, CM-IgG significantly alleviated hepatocellular morphology alterations and down-regulated GST-P gene expression levels in liver. Our results revealed the potential role of total immunoglobulin IgG purified from camel milk in amelioration of DENA-induced hepatocellular dysfunction and oxidative stress in hepatocarcinoma-bearing rats.

Terpenoids from Azadirachta indica are potent inhibitors of Akt: Validation of the anticancer potentials in hepatocellular carcinoma in male Wistar rats.

Hepatocellular carcinoma (HCC) is the commonest primary malignancy with poor patient prognosis and a high mortality rate. In this study, phytochemicals characterized from Azadirachta indica were screened against the catalytic site of Akt, and the anticancer potentials of the extracted leads (terpenoids) were determined in hepatocellular carcinoma in male Wistar rats. The lead compounds are terpenoids; hence, the extraction of terpenoids from A. indica. Gas chromatography-mass spectrometry (GCMS) was employed for the characterization of the extract. Diethylnitrosamine (DEN)-induced hepatocellular carcinoma in male Wistar rats were treated with the terpenoids extract. The hit, lupeol demonstrates inhibition of Akt and is a potential drug candidate. The terpenoids extract downregulate Akt mRNA and demonstrated anti-Akt downstream signaling effects; anti-inflammatory, anti-angiogenesis, pro-apoptotic, and cell cycle arrest, it also demonstrated cellular regeneration, hepatoprotection, antioxidant potentials, and cellular repairs in hepatocellular carcinoma in male Wistar rats. PRACTICAL APPLICATIONS: Hepatocellular Carcinoma (HCC) is the most common primary malignancy with poor patient prognosis and a high mortality rate. Akt, a serine/threonine kinase is at the crossroad of cell survival, the progression of the cell cycle, cell signaling, cell growth, cell division, and inactivation of pro-apoptotic factors. The inhibition of Akt is an effective therapeutic strategy against HCC. In this study, terpenoids from Azadirachta indica are potent inhibitors of Akt and hitherto demonstrate anticancer potentials. A. indica leaves are readily available globally and more also it is readily cultivated in African and Asia, continents with the highest prevalence of HCC. A. indica terpenoids extract demonstrate anti-HCC potentials and hence should be exploited in this regard.

103 Poster - Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine induced hepatocellular carcinoma in male wistar rats

103 Poster - Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine induced hepatocellular carcinoma in male wistar rats

Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats

BackgroundHepatocellular carcinoma (HCC) is a common and leading cancer around the globe. This study investigated the anticancer properties of extract of Annona senegalensis in N-diethylnitrosamine (DEN) - induced hepatocellular carcinoma in male Wistar rats. MethodsRats were simultaneously induced with a combination of 100 mg/kg b.wt of DEN and 0.5 mL/kg of carbon tetrachloride (CCl4) intraperitoneally once a week for three weeks in a row. Thereafter, animals were treated with 100 mg/kg and 200 mg/kg b.wt of A. senegalensis extract daily for 21days. Analysis using gas chromatography-mass spectrometry (GC–MS) was carried out to discover the phytoconstituents contained in the n-hexane extract of A. senegelensis. The levels of liver function parameters and antioxidant enzyme activities were determined via spectrophotometric analysis. Reverse transcriptase-polymerase chain reaction technique was used to assess the gene expression patterns of BCL-2, P53, P21, IL-6, FNTA, VEGF, HIF, AFP, XIAP, and EGFR mRNAs. ResultsTreatment of DEN-induced hepatocellular carcinoma Wistar rats with the extract caused significant (p < 0.05) decrease in the activities of ALT and AST. It also resulted in a reduction of the concentration of MDA and a significant increase (p < 0.05) in SOD and GSH activities. IL-6, BCL-2, VEGF, EGFR, XIAP, FNTA, and P21 mRNAs expressions were significantly (p < 0.05) downregulated after treatment. Histopathological analysis revealed that the extract improved the liver architecture. ConclusionA. senegelensis n-hexane extract demonstrates its anticancer properties by improving the liver architecture, increasing the antioxidant defense systems, downregulating the pro-inflammatory, anti-apoptotic, angiogenic, alpha-fetoprotein and farnesyl transferase mRNAs expression and hitherto up-regulate the expression of tumor suppressor (P21 and P53) mRNAs.

Anticarcinogenic potential of ethanol extract of Indigofera cordifolia Roth. (Fabales: Fabaceae) on diethylnitrosamine induced hepatocarcinogenesis in rats

Indigofera cordifolia Roth. (Fabales: Fabaceae) has been widely used in Indian system of medicine to treat various disorders. Earlier studies showed that I. cordifolia (EIC) possess antioxidant, free radical scavenging and antitumour activities. The present investigation was designed to evaluate the anticarcinogenic potential of EIC against diethylnitrosamine (DEN) induced hepatocellular carcinoma in male Wistar rats. Hepatocarcinogenesis was induced by a single intraperitoneal administration of DEN (200 mg/kg) and the carcinogenic effect was promoted by phenobarbital given through drinking water for 16 successive weeks. EIC at the dose of 200 and 400 mg/kg/day were administered orally for the entire study period. After the end of experimental period, changes in body weight, the weight of liver, relative liver weight, lipid peroxidation, antioxidant, serum hepatic parameters, tumour markers, DNA, RNA and protein content were analysed. Treatment with EIC significantly increased the body weight (P &lt; 0.01-0.001), reduced the liver weight and relative liver weight (P &lt; 0.01-0.001), restored the altered serum hepatic parameters (P &lt; 0.001), down-regulated the serum tumour markers such as alpha-fetoprotein and carcinoembryonic antigen (P &lt; 0.001) when compared to DEN group. EIC treatment restored the antioxidant enzymes and significantly reduced the lipid peroxidation in DEN-treated animals (P &lt; 0.001). EIC treatment also significantly reduced the elevated levels of nucleic acid levels and restored the protein content in liver tissues (P &lt; 0.001). We investigated the anticarcinogenic potential of EIC against DEN-induced HCC in rats. Chemoprotective effect of the extract might be related with antioxidant, free radical scavenging and reduction of lipid peroxidation. The results suggested that EIC would be a potent anticarcinogenic agent inhibiting DEN-induced hepatic carcinoma.

Decreased Hepatic 5-HT1A Receptors During Liver Regeneration and Neoplasia in Rats

In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A receptor during liver regeneration after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.

Oesophageal neoplasia in male Wistar rats due to parenteral di(2-hydroxypropyl)-Nitrosamine (DHPN): a combined histopathological, histochemical and electron microscopic study.

Intraperitoneal di(2-hydroxypropyl)-Nitrosamine (DHPN) caused a high incidence of oesophageal squamous carcinoma in male Wistar rats, particularly in rats killed 11 or more months after the start of injections. No control rats (injected intraperitoneally with saline) developed an oesophageal neoplasms. Histopathologically, the tumours were moderately well differentiated. Histochemical studies showed minor increases in mucin staining and mast cell population and a marked increase in bacteria in tumour-bearing oesophaguses. Electron microscopy showed the tumours to be similar to, but to differ in some respects from squamous carcinomas at other sites in humans. The possible implications of this work for human disease are twofold. It could provide a model for further study of aspects of oesophageal carcinoma and it serves to remind us that all potential oesophageal carcinogens need not act during swallowing.