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Background: Colon cancer is rising among younger population than elder people. About 50% of colon cancer cases attributed to dietary factors. Monosodium glutamate (MSG) widely used taste enhancer prevalent in fast foods and processed items. Objectives: The study investigated into the potential toxic and carcinogenic role of MSG in male Wistar rats of 1–3 months old and compared the effects with the Dimethyl hydrazine (DMH): by observing survival probability, estimation of serum biochemical parameters, and analysis for colon beta catenin protein expression. Methods: Rats were grouped into control, DMH (s.c), low- and high dose MSG (LDMSG, HDMSG) (p.o). Survival rate statistically calculated using Kaplan-Meier plots and Log-rank tests. Biochemical analyses were done using standard protocols and one-way ANOVA were performed for data analysis. Beta catenin protein expressions were studied using immunohistochemistry and western blotting. Results: Our study emphasizes that high dose MSG consumed male Wistar rats cause high decline in survival rate compared to low dose MSG and DMH. Estimated serum biochemical parameters showed significantly increased oxidative stress, altered liver and kidney function markers, alongside elevated serum sodium, total cholesterol, triglycerides, LDL, and inflammatory markers. Observed, colon polyps formed in DMH and MSG rats. Rat’s colon immunohistochemistry study expressed β- catenin whereas Western blotting results confirmed the altered β- catenin and β-catenin phosphorylation ratios in cytosol and nuclear region were elevated in DMH-induced colon cancer (p value of 0.0002), MSG low dose (p value of 0.003) and high dose (p value of 0.01) statistically significant. These findings highlights declined survival probabilities and pronounced oxidative stress markers, organ function changes, disrupted lipid profiles, and increased nuclear β-catenin expression reveals the potential toxic and carcinogenic role of MSG is influencing colon cancer development in male Wistar rat models. Conclusion: Based on the results, the study underscores the potential toxic and carcinogenic role of MSG, particularly at neoplastic stages of colon cancer in male Wistar rat models.

Colorectal cancer, which is the third leading cause of cancer‐related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel‐forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1−/−) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1−/− female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2‐dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub‐acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH‐induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase‐3) in colonic crypts. Of note, at week 37, Panx1−/− animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a dangerous oncological disease that requires serious complex treatment. This type of oncopathology occurs due to atypical growth of the epithelium of the mucous layer that lines the intestinal walls. Colon cancer is characterized by slow development, so prevention and timely diagnosis are a priority. The main advantage of using oncoprotectors based on natural raw materials in clinical practice is their low toxicity and the possibility of long-term use without significant side effects. That is why the development and study of such drugs are relevant. The aim of the research was to study indicators of oxidative processes and antioxidant systems in rats with chemically induced colon carcinogenesis against the background of maitake mushrooms thick extract use. The study was performed on 120 white male rats weighing 190–210 g. Adenocarcinoma of the colon was modeled by administering 1,2-dimethylhydrazine (DMH) hydrochloride for 30 weeks (1 time per week). A thick extract from maitake mushrooms was administered intragastrically daily at a dose of 150 mg/kg of animal body weight. Blood and liver samples were taken for research monthly. The state of the pro- and antioxidant systems was studied by the content of oxidative modification of proteins products neutral and alkaline character, superoxide dismutase and catalase activity, contents of reduced glutathione and ceruloplasmin. It was found that DMH-induced colon carcinogenesis in rats is accompanied by an increase in the activity of free radical oxidation processes. It is evidenced by a decrease in superoxide dismutase activity, catalase activity, a significant reduction in the content of reduced glutathione, an increase in the content of ceruloplasmin and products of oxidative modification of proteins in the blood serum and liver of animals. The effectiveness of maitake mushrooms thick extract and its positive influence on the activity of the studied enzymes and the content of OMP products in investigated tissues was experimentally proved. The use of maitake mushrooms thick extract under conditions of DMH-induced colon carcinogenesis in rats led to the normalization of antioxidant protection indicators and a significant decrease in the indicators of oxidative modification of proteins, which testifies to the suppression of oxidative stress in animals with an oncological process.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats.

Background. Every year the number of cases of colorectal cancer increases. Chemotherapy is one of the main methods of treating cancer. However, chemotherapeutic treatment of colorectal cancer is inextricably linked to hepatotoxic reactions. Objective. The aim of this study was to investigate the effect of the cytostatic vincristine on the background of previous enterosorption correction with the drug aut-m in adenocarcinoma of the colon. Material and methods. To simulate carcinogenesis, dimethylhydrazine (DMH) was administered subcutaneously to 77 rats for 30 weeks at a dose of 7.2 mg/kg body weight. After simulation of colon cancer, the animals were intragastricly administered entorosorbent at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal, daily for 21 days. After detoxification therapy, rats with simulated carcinogenesis were administered the daily cytostatic vincristine at a dose of 0.23 mg/kg for 14 days. Results. It was found that prolonged administration of dimethylhydrazine is accompanied by destructive changes in plasma membranes, as evidenced by increased activity of enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and serum urea. Conclusions. The used sorbent aut-m showed an effective effect on reducing the manifestations of cytolytic processes in induced carcinogenesis, as indicated by the normalization of the studied parameters. The cytostatic vincristine, which was used in rats with induced colorectal cancer after enterosorption therapy, did not significantly affect the enhancement of cytolytic processes, which confirms the effectiveness of previous sorption measures under these conditions.

Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml. Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer. [Display omitted] • Cancer is a leading cause of death globally; mortality has risen by nearly 40% in 40 years. • Rheum webbianum Royle (RW) shows therapeutic benefits including cancer treatment. • RW extracts impact HCT-116 cell viability dose-dependently, suggesting cytotoxic effects. • RW extracts suppress colorectal cancer progression in DMH-induced rat models. • Effectively restored hematological parameters, reduced hepatic degradation and oxidative stress. [ABSTRACT FROM AUTHOR]

Cancer is emerging as one of the most significant challenges to the human health. Ivermectin (IVM) is one of the most effective drugs in veterinary and human medicine. The purpose of this study was to evaluate the potential preventative effect of IVM against cytotoxicity induced by dimethylhydrazine (DMH) in Male Wistar rats. Three concentrations of IVM (0.25, 0.5 and 1 mg/kg) were utilized in this study. Liver function enzymes, inflammatory markers and histopathological alterations in liver and kidney tissues were investigated. Obtained data showed that the combination of DMH with each concentration of IVM increased the activity of liver enzymes (ALT, ALP, AST, and GGT) compared to control and DMH alone. RT-PCR findings showed upregulation in the level of INF-γ, IL-6, IL-1β, Cox1, and Cox2 genes compared to control. In contrast, IL-6 gene was down-regulated. The levels of genes expression were down-regulated with combined DMH with medium and high concentrations compared to DMH alone. Microscopic analysis demonstrated histological alterations in the liver and kidney of rats treated with DMH. Combinations of DMH either with medium or high concentration resulted in less pathological features in both liver and kidney tissues. In conclusion, this study showed that IVM mitigated the toxic effects of DMH on the liver and kidney of male Wistar rats.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD 50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer is the world's third most prevalent cancer. Herbal drugs are increasingly being used to treat a variety of disorders, including cancer, due to the severe adverse effects. Harmol, natural molecule containing β-carboline alkaloids, has aroused the interest of researchers due to its diverse biological functions, including anticancer properties. Methods: In this study, the chemotherapeutic effects of harmol have been investigated on HT-29 colon cancer cell line and a rat model of colon cancer. In the in vitro study the cytotoxicity assay, DAPI analysis and the flow cytometric analysis was performed to assess the anticancer efficacy of harmol in HT-29 cell. The colorectal cancer was developed in male Wistar rats through the administration of DMH followed by treatment with DSS. The rats were treated with harmol (100, 200 and 400 mg/kg) for 18 weeks. At the end of therapy, the colon tissues were assessed for ACF, in vivo antioxidant activity, histopathology, immunohistochemistry, immunofluorescence analysis and apoptosis assay. Results: The in vitro data suggested that the harmol therapy would significantly increase the percentage of early apoptosis in HT-29 cells through halting of G0/G1 phase. Furthermore, inhibition of ACF development with improved colonic abrasion and morphological features in colonic mucosal region were noted. Harmol treatment also increased the levels of antioxidants and p53 and downregulated Bcl2, IL-6 and TNF-α expression. Conclusion: These outcomes signify that harmol successfully recover colorectal carcinoma by reprogramming the p53, Bcl2, IL-6 and TNF-α pathway in rats. [ABSTRACT FROM AUTHOR]

Colorectal cancer is considered the third most common cancer and the second leading cause of death globally. It has been proven that titanium dioxide nanoparticles produce oxidative stress and can lead to chronic inflammation, which could turn into diseases like cancer, cardiovascular disorders, diabetes, and so on. To evaluate the effect of 5-fluorouracil (5-FU) curcumin (CUR) conjugate coated with pectin on colorectal cancer induced by titanium dioxide nanoparticles (TiO2-NPs) and dimethylhydrazine (DMH), male rats were administered TiO2-NPs (5 mg/kg) orally and DMH (1 mg/kg) peritoneally for 70 days and treated with 5-FU (60 mg/kg) and CUR (240 mg/kg) conjugate (1:4 ratio) coated with pectin. The bodyweight of the animals was evaluated, and the blood sugar level was calculated. Further blood and plasma analyses were conducted. Hematological parameters, antioxidant parameters, and biochemical estimation were taken into consideration. The TiO2-NPs level in the blood and colorectal region was also calculated. With the induction of colon cancer using TiO2-NPs and DMH, a significant increase in the body weight of the animals was seen; eventually, with treatment, it was reduced. The bodyweight increase was due to an increase in the blood sugar level. There were also significant changes in the hematological parameters and biochemical estimation reports when comparing those of the positive control, negative control, and treated groups. No significant effect on biochemical estimation reports was seen. Conclusions: These reports suggest that 5-FU CUR conjugate coated with pectin helps in the management of colorectal cancer induced by TiO2-NPs and DMH. [ABSTRACT FROM AUTHOR]

Quantification of unsymmetrical dimethylhydrazine transformation products in solid samples is an important stage in monitoring of environmental pollution caused by heavy rockets launches. The new method for simultaneous quantification of unsymmetrical dimethylhydrazine transformation products in sand samples using vacuum-assisted headspace solid-phase microextraction without addition of water followed by gas chromatography-mass spectrometry is proposed. Decreasing air evacuation time from 120 to 20 s at 23 °C resulted in increased responses of analytes by 25–46% and allowed obtaining similar responses as after evacuation at −30 °C. The best combination of responses of analytes and their relative standard deviations (RSDs) was achieved after air evacuation of a sample (m = 1.00 g) for 20 s at 23 °C, incubation for 30 min at 40 °C, and 30-min extraction at 40 °C by Carboxen/polydimethylsiloxane (Car/PDMS) fiber. The method was validated in terms of linearity (R2=0.9912–0.9938), limits of detection (0.035 to 3.6 ng g−1), limits of quantification (0.12–12 ng g−1), recovery (84–97% with RSDs 1–11%), repeatability (RSDs 3–9%), and reproducibility (RSDs 7–11%). It has a number of major advantages over existing methods based on headspace solid-phase microextraction—lower detection limits, better accuracy and precision at similar or lower cost of sample preparation. The developed method was successfully applied for studying losses of analytes from open vials with model sand spiked with unsymmetrical dimethylhydrazine transformation products. It can be recommended for analysis of trace concentrations of unsymmetrical dimethylhydrazine transformation products when studying their transformation, migration and distribution in contaminated sand. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer is the world's third most prevalent cancer. Herbal drugs are increasingly being used to treat a variety of disorders, including cancer, due to the severe adverse effects. Harmol, natural molecule containing β-carboline alkaloids, has aroused the interest of researchers due to its diverse biological functions, including anticancer properties. Methods: In this study, the chemotherapeutic effects of harmol have been investigated on HT-29 colon cancer cell line and a rat model of colon cancer. In the in vitro study the cytotoxicity assay, DAPI analysis and the flow cytometric analysis was performed to assess the anticancer efficacy of harmol in HT-29 cell. The colorectal cancer was developed in male Wistar rats through the administration of DMH followed by treatment with DSS. The rats were treated with harmol (100, 200 and 400 mg/kg) for 18 weeks. At the end of therapy, the colon tissues were assessed for ACF, in vivo antioxidant activity, histopathology, immunohistochemistry, immunofluorescence analysis and apoptosis assay. Results: The in vitro data suggested that the harmol therapy would significantly increase the percentage of early apoptosis in HT-29 cells through halting of G0/G1 phase. Furthermore, inhibition of ACF development with improved colonic abrasion and morphological features in colonic mucosal region were noted. Harmol treatment also increased the levels of antioxidants and p53 and downregulated Bcl2, IL-6 and TNF-α expression. Conclusion: These outcomes signify that harmol successfully recover colorectal carcinoma by reprogramming the p53, Bcl2, IL-6 and TNF-α pathway in rats. [ABSTRACT FROM AUTHOR]

White tea (WT) has the highest amount of catechin which previously was found to enhance anti-cancer activity. To enhance the bioavailability of WT, silver nanoparticle (AgNP) was used to synthesize WT nanoparticle (WTNP). This present study aimed to determine the effectiveness of WTNP alone and co-administered with 5FU in the prophylactic study. WTNP was characterized by UV–Vis spectra, X-ray diffraction (XRD) spectra, transmission electron microscope (TEM) and Fourier-transform infrared spectroscopy (FTIR) and tested for their acute toxicity. In animal studies, all groups except the naïve group were given once a week 65 mg/kg of 1,2-dimethylhydrazine (DMH) subcutaneously, intraperitoneal injection of 50 mg/kg 5FU and daily administration of DMH 50 mg/kg WT and 5FU WTNPs. Aberrant crypt foci (ACF) and histology were determined and analysed. WTNP showed circular and pseudospherical shaped and 25–50 nm size range with no acute toxicity observed on rats. The DMH group was the highest in average ACF count (37.3 ± 3.18), which ACF was shown to decrease using the treatment, WT group (16.67 ± 3.28), 5FU monotherapy (5.67 ± 2.19) and WTFU (6.33 ± 1.33). The highest AC frequency was found at the DMH group (24.67 ± 1.20, 12.67 ± 1.45) compared to other groups. The chemo-suppressive effect of WTNP and WTFU combined effects was observed in the present study. WTNP expresses anti-cancer properties; however, it does not produce any synergistic effect. [ABSTRACT FROM AUTHOR]

Aim: Cancer is one of the leading causes of death in the world. The aim of this research was to study the indices of pro- and antioxidant systems in rats with dimethylhydrazine (DMH)-induced colon carcinogenesis on the background of the enterosorbent AUT-M use. Materials and methods: The study was performed on 70 white male rats weighing 200–250 g. Adenocarcinoma of the colon was simulated by subcutaneous injection of the DMH (Sigma-Aldrich Chemie, Japan) at a dose of 7.2 mg/kg once a week during 7 months. Enterosorbent AUT-M was administered intragastrically daily for 21 days after simulation of carcinogenesis at a dose of 1 ml of suspension per 100 g of animal body weight. The state of the pro- and antioxidant systems was studied by the content of oxidative modification of proteins products (OMP), the activity of superoxide dismutase (SOD), catalase (CAT), contents of ceruloplasmin (CP) and reduced glutathione (GSH). Results: It was found that DMH-induced colon carcinogenesis in rats is accompanied by disorders in the antioxidant defense system and activation of free radical oxidation processes. Enterosorbent AUT-M provides a significant reduction in the content of OMP370 and OMP430 in both blood serum and liver homogenate of rats. Moreover, the use of enterosorbent AUT-M demonstrated a significant increase in the activity of SOD, CAT, content of GSH and a decrease in CP content in investigated tissues. Conclusion: The use of enterosorbent AUT-М demonstrated prominent potential suppression for oxidative stress and positive effect on antioxidant defense system in rats with DMH-induced colon carcinogenesis. [ABSTRACT FROM AUTHOR]

We investigated the effects of karanjin on dimethylhydrazine (DMH) induced colon cancer in rats. Male Wistar rats were injected with DMH followed by dextran sodium sulfate in drinking water for 7 days. Karanjin at doses of 50,100 and 200 mg/kg was administered orally for 18 weeks. Colon tissues were investigated using TUNEL analysis of apoptosis; histopathological assessment including number of aberrant crypt foci (ACF); immunohistochemical staining for Bcl-2-associated X protein (BAX), B-cell lymphoma 2 (Bcl2), p53 and proliferating cell nuclear antigen (PCNA); and antioxidant assay in vivo. We found that treatment with karanjin inhibited formation of ACF in the colon mucosa and reduced colon lesions. Karanjin treatment also increased the antioxidants, catalase, glutathione and superoxide dismutase. Immunostaining showed that karanjin treatment reduced BAX, p53 and PCNA levels and increased Bcl2 expression. The TUNEL assay revealed that karanjin induced apoptosis in the colon mucosa. Our findings suggest that karanjin can ameliorate colon carcinogenesis in rats by regulating BAX, Bcl2 and p53 pathways. [ABSTRACT FROM AUTHOR]

Bavachinin is a flavanone obtained from the Chinese herb, Fructus Psoraleae. Flavonoids and flavanones are recognized as cancer preventive agents. We investigated the anticancer properties of bavachinin using a model of dimethylhydrazine (DMH and dextran sodium sulfate (DSS) induced rat colon cancer. We investigated aberrant crypt foci (ACF), hyperplastic lesions, catalase (CAT), superoxide dismutase (SOD) and glutathione (GST) levels in Wistar rats. Expression of cancer biomarkers including IL-6, p53, Bcl2 and BAX was investigated. We found that bavachinin administered to rats re-established the colonic crypts that were damaged by DMH and prevented progression of the cancer. [ABSTRACT FROM AUTHOR]

Objective: This study examined the morphological changes in the colonic mucosa and the presence of inflammation in rats induced with 1,2-dimethylhydrazine (DMH) 30 mg/kg BW over 9, 11, and 13 weeks without a latency period., Methods: Hematoxylin and eosin staining was performed to assess the morphology and characteristic alteration of the epitheliocytes in the colon. Immunohistochemistry was employed to assess the expression of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2). The difference in the severity of inflammation and COX-2 expression was examined using one-way analysis of variance. The correlation of COX-2 expression with the severity of inflammation was analyzed using Spearman's rank correlation test., Result: Until week 13, chronic inflammation and non-hyperplastic and hyperplastic aberrant crypt foci occurred. The severity of inflammation gradually shifted from high moderate to low moderate. TNF-α expression was high in all groups; however, COX-2 expression was gradually lower with longer duration of induction, which corresponded with the severity of inflammation., Conclusion: DMH induction until week 13 without a latency period caused chronic inflammation without the formation of adenoma or adenocarcinoma. A very strong correlation was established between COX-2 expression and inflammation.

This study aimed to investigate the effect of theobromine on dimethylhydrazine (DMH)-induced colon cancer. Male Wistar rats were divided into four groups and injected with saline (negative control) or 30 mg/kg DMH (other three groups) two times a week for 12 weeks. The negative control and DMH-treated control rats were treated with water and the other two groups with theobromine, at the dose of 100 or 200 mg/kg, two weeks before and during the period of injection. Both doses of theobromine reduced the volume and number of tumors, the number of aberrant crypts, and the expression of p-Akt, p-GSk3β, and cyclinD1, and also increased the expression of APC tumor suppressor. A significant reduction in the expression of β-catenin was observed in the rats treated with the high dose of theobromine. The results indicated that theobromine may be an effective chemopreventive agent for colon cancer by inhibition of the Akt/GSk3β/β-catenin pathway.

Dimethylhydrazine (DMH) is a potent colonic and hepatic carcinogen that is metabolized into oxyradicals causing liver injury and DNA mutations. Matricaria chamomilla is a well-documented medicinal herb that possesses anti-inflammatory, antioxidant and antitumor activities and is commonly used to treat diverse ailments. The present study aimed to reveal the hepatoprotective effects of Matricaria chamomilla aqueous extract during an intermediate stage of colorectal cancer (CRC) in mice. Male Balb/c mice were divided into six groups: group A served as control, group B received chamomile extract (150 mg/Kg b.w.) orally for 12 weeks, and groups C-F received weekly intraperitoneal injections of DMH (20 mg/Kg b.w.) once a week for 12 weeks. In addition to DMH, groups D and F received chamomile during the initiation and post-initiation stages, respectively. Blood and liver samples were collected for biochemical and molecular analyses. The results showed that DMH induced hepatic injury in mice as shown by significant increase in serum aspartate aminotransferase and alanine aminotransferase. The changes in biochemical parameters were accompanied by activation of the Wnt signaling pathway leading to increased hepatocytes proliferation as well as inflammation evidenced by high levels of pro-inflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). The results also showed potential hepatoprotective effects of chamomile extract against DMH-induced liver injury, proliferation and inflammation. Chamomile restored the biochemical and molecular parameters and this improvement was more pronounced in mice pretreated with the extract. In conclusion, chamomile extract may exert its hepatoprotective activities against DMH probably due to the antioxidant, antiproliferative and anti-inflammatory properties of its flavonoids.

Encapsulation techniques and materials, explored for addressing compromised probiotic gut survival, report significant production losses resulting in <10% entrapment. Presently, we report three-time enhanced entrapment (30 ± 1.2%) of Lactobacillus acidophilus (LAB) in calcium-alginate beads, by modifying process parameters and employing polyethylene glycol (PEG). Water-loving, viscolysing and osmotic-building effects of PEG create numerous, fine voids in the alginate gel allowing efficient diffusion of crosslinking calcium ions, resulting in less leaky beads. Eudragit S100 overcoat improved LAB survival by 690 times in simulated GIT stresses. In DMH-DSS induced colitis and precancerous lesions in rats, while free LAB failed to show any protection, pharmabiotic beads significantly (p <.05) reduced lipid peroxidation, increased antioxidant levels; decreased serum inflammatory burden; downregulated COX-2, iNOS, and c-Myc expression; elevated levels of the selected gut bacteria and SCFAs especially butyrate, all of which add up to antioxidant, anti-inflammatory, balanced gut biota, and ultimately anticancer effects. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer is a disease that occurs from three major pathways: sporadic, hereditary, and inflammatory. Carica pubescens (CP) have potential chemopreventive effects. This study wants to determine the effect of CP leaf extract on the neutrophil-lymphocyte ratio (NLR), erythrocyte count, and colon histopathological appearance of rats induced by dimethylhydrazine (DMH). Methods: The samples were Sprague Dawley rats (n=35, male, 5-7 weeks aged, 150-200 grams). NC was the normal control group. The DMH group was induced by 20 mg/kg BW of DMH (subcutaneously) once a week for 15 weeks. CP75, CP150, and CP300 were induced by DMH and given CP leaf extract orally at doses of 75, 150, and 300 mg/kg BW, once daily for 15 weeks. The neutrophil, lymphocyte, and erythrocyte count were measured using hematology analyzer. The histopathological appearance shows the percentage of total aberrant crypt foci, and the degrees of inflammation cells. Results: The NLR of CP75 (0,23±0,042), CP150 (0,26±0,018), and CP300 (0,21 ±0,039) was significantly lower than DMH (0,64±0,239), p<0,001. The erythrocyte count of CP150 (8,89±1,082 x106 cell/µL; p=0,034) and CP300 (9,24±0,396 x106 cell/µL; p=0,006) was significantly higher than DMH (7,87±0,641 x106 cell/µL). The percentage of total aberrant crypt foci of CP75 (15,71 ±5,345%,p=0,006), CP150 (18,57±6,901%,p=0,014), and CP300 (5,71 ±5,345%,p=0,001 ) was significantly lower than DMH (59,29±32,714%). Conclusion: Carica pubescens leaf extract may reduce the neutrophil-lymphocyte ratio, percentage of total aberrant crypt foci and inflammation degree in colon histopathological appearance, otherwise increase the number of erythrocyte in DMH-induced colon cancer rats. [ABSTRACT FROM AUTHOR]

Aseries of cyclobutane-1,1,2,2-tetracarbonitriles contained a compound with significant activity against various cancer cell lines. The compound featured a thiosemicarbazide and the α,β-unsaturated aldehyde myrtenal in its structure and showed the highest activity against leukemia cells, the average growth inhibition against which was 88%. The proposed mechanism of action was associated with alkylation of the nucleophilic regions of tumor-cell DNA. The results showed that compounds with an ethyl-1,1,2,2-tetracarbonitrile fragment inhibited proliferation of malignant cells. [ABSTRACT FROM AUTHOR]

Anti‐inflammatory drugs are well known to reduce the risk of colon cancer and prophylactic use of such agents is gaining acceptance as a cancer prevention therapy. As artesunate, an antimalarial drug, has been shown to exhibit chemopreventive properties, the present study was carried out to evaluate its inhibitory effect on oxidative stress and inflammation in a rat model of colon carcinogenesis. A chemical carcinogen, 1,2‐dimethylhydrazine was injected twice at an interval of 1 week to induce preneoplastic lesions in the colon and the parameters indicating oxidative stress and inflammation were evaluated after 8 weeks. Artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) were administered orally throughout the study. Analysis of colon tissue revealed that both the drugs preserved histoarchitecture, inhibited cellular influx, decreased the levels of oxidative stress and inflammatory markers, downregulated cyclooxygenase‐2, inducible nitric oxide synthase, nuclear factor κB, and interleukin 1β in comparison to the experimental control. Suppression of oxidative stress and pro‐inflammatory signaling by both the drugs were found to contribute to inhibition of colon carcinogenesis. The protection afforded by these drugs was found to be comparable. Our study shows that like aspirin, use of artesunate could also reduce the risk of colon cancer and it has a potential for further evaluation for the treatment purpose. [ABSTRACT FROM AUTHOR]

A new, sensitive and simple method based on vacuum-assisted headspace solid-phase microextraction (Vac-HSSPME) followed by gas chromatography-mass-spectrometry (GC–MS), is proposed for the quantification of rocket fuel unsymmetrical dimethylhydrazine (UDMH) transformation products in water samples. The target transformation products were: pyrazine, 1-methyl- 1H -pyrazole, N -nitrosodimethylamine, N , N -dimethylformamide, 1-methyl- 1Н -1,2,4-triazole, 1-methyl-imidazole and 1H -pyrazole. For these analytes and within shorter sampling times, Vac-HSSPME yielded detection limits (0.5–100 ng L −1 ) 3–10 times lower than those reported for regular HSSPME. Vac-HSSPME sampling for 30 min at 50 °C yielded the best combination of analyte responses and their standard deviations (<15%). 1-Formyl-2,2-dimethylhydrazine and formamide were discarded because of the poor precision and accuracy when using Vac-HSSPME. The recoveries for the rest of the analytes ranged between 80 and 119%. The modified Mininert valve and Thermogreen septum could be used for automated extraction as it ensured stable analyte signals even after long waiting times (>24 h). Finally, multiple Vac-HSSME proved to be an efficient tool for controlling the matrix effect and quantifying UDMH transformation products. [ABSTRACT FROM AUTHOR]

Zinc is a trace element widely known for its marked antioxidant properties. To gain more insight into the site- and time- specific mechanisms by which it induces chemoprevention, this study was elaborated over a pre-cancerous model of colon carcinogenesis. Colon cancer was induced by 1,2-dimethylhydrazine (DMH) in mice (20 mg/kg for 2 weeks) and groups of animals were supplemented with or without zinc sulfate (ZnSO 4 , 200 mg/L) in drinking water for 4, 10 or 14 weeks. Colon tissues were collected for pathological observation, analyzing aberrant crypt (AC) and aberrant crypt foci (ACF) formations, multiplicity and distribution. Similarly, histological assessment and mucin production, as well as oxidative stress markers estimation was performed for the different groups. Results showed a significant increase in ACF and AC numbers, ACF multiplicity and demonstrated stronger distal occurrence than in the proximal after DHM administration. Histopathological analysis presented marked structural alterations and mucin loss in the distal than the proximal colons. A significant increase in myeloperoxidase (MPO), nitric oxide (NO), L-ornithine and malondialdehyde (MDA) levels was observed followed by a significant decrease in antioxidant markers (superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)). Oral ZnSO 4 supplementation (continuous or partial) induced significant decrease in ACF, AC numbers and multiplicity, restored histological architecture and mucin production, and a significant decrease in proinflammatory markers while it reduced antioxidants to normal levels. From this study, insight was obtained on the use of ZnSO 4 as a chemopreventive agent and shed light on its potential, as a supplement in nutraceutical approaches. [ABSTRACT FROM AUTHOR]

Transplantation of placenta-derived multipotent cells (PDMCs) is a promising treatment method for many diseases. However, the impact of PDMCs on colon cancer has not yet been studied. PDMCs were obtained from rat placentas by culturing tissue explants. Colon cancer was experimentally induced in male albino Wistar rats by administering 20 mg/kg dimethylhydrazine (DMH) once a week for 20 consecutive weeks. The administration of the PDMCs was performed at the 20th week after the first DMH injection. The number and size of each tumour lesion were calculated in the 5th week after transplantation. The tumour type was determined by standard histological methods. To study the engraftment of PDMCs in the body of rats, the cells were transduced with enhanced green fluorescent protein. Cell engraftment was determined by assessing the presence of EGFP by PCR and immunohistochemistry. Survival of all rats was monitored daily. Allogeneic transplantation of PDMCs to rats at middle phase of DMH-induced colon carcinogenesis did not significantly influence the number of neoplasms and the parameters of mean and total tumour area, but led to an increase in size of the most invasiveness tumours. Intravenous allogeneic transplantation of PDMCs reduced the survival rate of rats with colon cancer by 17 days. PDMCs from rats engrafted into tissues of the normal intestine, tumours, lungs, liver, and spleen of rats for five weeks after intravenous transplantation. These results suggest that intravenous allogeneic transplantation of PDMCs promotes colon cancer progression and has a negative impact on survival of rats. [ABSTRACT FROM AUTHOR]

Colon cancer is thought to develop in a stepwise fashion. In this study, the relationship between aberrant crypt foci (ACF) regional distribution and oxidative stress evolution was studied in a murine model of initial colon carcinogenesis induced by dimethylhydrazine (DMH). Mice were given 2 weekly subcutaneous injections of DMH (20 mg/kg) and killed at the 10th, 12th or 14th week. ACF was scored for number, distribution and crypt multiplicity after methylene-blue coloration and histologically analyzed afterwards. Oxidative stress evaluation was assessed through myeloperoxidase activity (MPO), nitric oxide (NO), l-ornithine and malondialdehyde (MDA) levels as well as antioxidant CAT, SOD and GSH. DMH treatment showed a shift from small to large ACF but also from distal to proximal colon between week 10 and 14 (p < 0.05). This was further illustrated histologically with crypt disruption and mucin depletion. Oxidative stress imbalance was observed in all DMH-treated groups. All markers (MPO, MDA and NO) peaked at week 12 (p < 0.01) and decreased at week 14 (p < 0.05) while l-ornithine decreased through all protocol (p < 0.01). Antioxidants decreased in all points (p < 0.05) but only GSH increased at week 14 (p < 0.05). This work provided insight to response-patterns of oxidative stress between distal and proximal colon, showing for the first time a decreasing implication during the development process and suggesting other inflammatory, immunologic or microbiota implication as factors to be considered during chemotherapy approaches. [ABSTRACT FROM AUTHOR]

Maslinic acid triggers compelling antiproliferative and pro-apoptotic effects in different human cancer cell lines. Hence, the chemopreventive activity was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH) which is a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either maslinic acid at 5, 10 or 25 mg/kg dissolved in (2-hydroxypropyl)-β-cyclodextrin 20% (w/v) or the solvent for 49 days. After one week of treatment, animals received three weekly intraperitoneal injections of DMH at the dose of 20 mg/kg. Maslinic acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg in a 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of maslinic acid found in the colon and the reduction of ACF (r = 0.999, p = 0.019) and MDF (r = 0.997, p = 0.049). The present findings demonstrate that maslinic acid induced an inhibition of the initiation stages of carcinogenesis. The assessment of this pentacyclic triterpene at the colon sheds light for designing diets with foods rich in maslinic acid to exert a chemopreventive activity in colorectal cancer.

Use of anti-inflammatory drugs is well known to decrease the risk of colorectal cancer, one of the most common causes of cancer related mortality. In view of anti-inflammatory property of artesunate reported in various experimental models, the present study was carried out to evaluate its efficacy in rat model where colon carcinogenesis was induced by 1, 2 dimethylhydrazine (DMH). A time course study revealed that two injections of DMH given at an interval of one week resulted in appearance of multiple plaque lesions and aberrant crypt foci in the colon with a peak effect occurring at the end of 8 weeks. An efficacy study carried out with daily oral administration of artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) showed a marked reduction in pre-neoplastic changes with a significant decrease in the number of aberrant crypt foci, crypt multiplicity and restoration of histoarchitecture. Both the drugs down regulated β-catenin signaling, reduced the levels of angiogenic markers like VEGF, MMP-9 and inhibited cellular proliferation. The anti-cancer effect of these drugs was concomitant with the pro-apoptotic effect as revealed by increased DNA fragmentation, TUNEL positivity and Bax/Bcl 2 immunoreactivity. This is the first study to evaluate the inhibitory effect of artesunate on pre-neoplastic changes in colon where its chemopreventive effect was found to be comparable to that of aspirin. Our study strengthens the previous findings and shows that it has a preventive and therapeutic potential in the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Presently, we explore a cobiotic-ginger extract (GE; antioxidant-antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally administered LAB looses viability while GE is a gastric irritant with poor ADME, we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and osmotic-building effects of polyethylene glycol were used to address poor probiotic encapsulation (≤10%) by effective sealing of numerous fine voids formed in the alginate gel. Beads were systematically optimized for maximum entrapment (92 ± 2.3% for GE, and 30 ± 1.2% for LAB) and sustained release, and were coated with eudragit-S100 for colonic-targetability, as established by in-vitro release. In-vivo evaluation in DMH-DSS induced colitis and precancerous lesions, in rats, indicated attenuation of oxidative stress (catalase, SOD, LPO) and inflammatory burden (IL-6 and TNF-α), and downregulation of COX-2 , iNOS , and c-Myc by both GE and LAB; restoration of colonic permeability by GE; and modulation of gut bacteria and SCFAs by LAB as the mechanisms of action. Complementing activities of GE and LAB in cobiotic beads lead to better reversals. Histology (H&E and toluidine blue) confirmed healing of precancerous lesions. [ABSTRACT FROM AUTHOR]

Quantification of trace concentrations of transformation products of rocket fuel unsymmetrical dimethylhydrazine (UDMH) in water requires complex analytical instrumentation and tedious sample preparation. The goal of this research was to develop a simple and automated method for sensitive quantification of UDMH transformation products in water using headspace (HS) solid-phase microextraction (SPME) in combination with GC-MS and GC-MS/MS. HS SPME is based on extraction of analytes from a gas phase above samples by a micro polymer coating followed by a thermal desorption of analytes in a GC inlet. Extraction by 85 µm Carboxen/polydimethylsiloxane fiber at 50 °C during 60 min provides the best combination of sensitivity and precision. Tandem mass spectrometric detection with positive chemical ionization improves method accuracy and selectivity. Detection limits of twelve analytes by GC-MS/MS with chemical ionization are about 10 ng L. GC-MS provides similar detection limits for five studied analytes; however, the list of analytes detected by this method can be further expanded. Accuracies determined by GC-MS were in the range of 75-125% for six analytes. Compared to other available methods based on non-SPME sample preparation approaches (e.g., liquid-liquid and solid-phase extraction), the developed method is simpler, automated and provides lower detection limits. It covers more UDMH transformation products than available SPME-based methods. The list of analytes could be further expanded if new standards become available. The developed method is recommended for assessing water quality in the territories affected by space activities and other related studies. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the key biochemical indexes associated with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy of a dietary polyphenol, ellagic acid (EA).Materials and Methods: Wistar rats were chosen to study objective, and were divided into 4 groups; Group 1-control rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group 3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH-induced Group 4 rats were initiated with EA treatment. We examined key citric acid cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and the activities of respiratory chain enzymes NADH dehydrogenase and Cytochrome-C-oxidase and membrane-bound enzyme profiles (Na +/K + ATPase, Ca 2+ ATPase and Mg 2+ ATPase), activities of lysosomal proteases such as β-D-glucuronidase, β-galactosidase and N-acety-β-D-glucosaminidase and cellular thiols (oxidized glutathione, protein thiols, and total thiols).Results: It was found that administration of DMH to rats decreased both mitochondrial and membrane-bound enzymes activities, increased activities of lysosomal enzymes and further modulates cellular thiols levels. Treatment with EA significantly restored the mitochondrial and ATPases levels and further reduced lysosomal enzymes to near normalcy thereby restoring harmful effects induced by DMH.Conclusion: EA treatment was able to effectively restore the detrimental effects induced by DMH, which proves the chemoprotective function of EA against DMH-induced experimental colon carcinogenesis. [ABSTRACT FROM AUTHOR]

. Colon cancer is one of the leading causes of cancer mortality, worldwide. Cancer stem cells are attractive targets for therapeutic interventions since their abnormal growth may trigger tumor initiation, progression, and recurrence. Colon cancer in rats were induced with 1, 2-dimethyl hydrazine (DMH) and treated with genistein, an isoflavone rich in the soy food products, which also possesses various biological activities. Genistein treatment regulates enzymatic and non-enzymatic anti-oxidants in the DMH-induced colonic tissue microenvironment. Alcian blue staining in colonic tissue reveals that mucin secretion was found to be depleted in DMH-induced group of animals. The alterations were normalized in the genistein-treated groups. Also, the mast cell population and collagen deposition were reduced as compared to induced group. Genistein treatment reduces the prognostic marker Argyrophilic nuclear organizer region (AgNOR) and proliferating cell nucleolar antigen (PCNA) in DMH-induced group of rats. DMH administration induces oxidative stress, whereas genistein activates nuclear factor-erythroid 2 related factor 2 (Nrf-2) and its downstream target hemoxygenase-1 (HO-1). Colonic stem cell marker protein CD133, CD44, and β-catenin expressions were found to be increased in DMH-induced group of animals as compared to control group of rats. Genistein treatment suppressed the expression of these stem cell markers suggesting rapid dysfunctional activation and proliferation of colonic stem cell-induced by DMH. The results of this study indicate that genistein administration in rats restored the colonic niche that was damaged by DMH and inhibits colon cancer progression. © 2016 BioFactors, 42(6):623-637, 2016 [ABSTRACT FROM AUTHOR]