Dimethylhydrazine Research Articles

Effects of karanjin on dimethylhydrazine induced colon carcinoma and aberrant crypt foci are facilitated by alteration of the p53/Bcl2/BAX pathway for apoptosis

ABSTRACT 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.

Pilot Study for Azoxymethane-induced Colon Cancer in Male Wistar Rats

<div class="WordSection1"><p><strong>Introduction </strong><strong>:</strong> The use of animal models could significantly further the elucidation of Colorectal Cancer (CRC) molecular pathogenesis and help in the discovery of preventive and therapeutic agents for the disease. Dimethylhydrazine (DMH) is a widely used chemical agent for Carcinogen induced CRC model. As agent, DMH is however becoming less readily available; hence in this Pilot Study we use Azoxymethane (AOM), a DMH metabolite as an alternative agent to induce CRC in male Wistar rats.</p><p> </p><p><strong>Methods:</strong> Forty two male Wistar rats at six weeks of age were randomly assigned into negative control groups and groups receiving two AOM injections subcutaneously (SC) within one week interval at 15 mg/kg body weight (BW) and 20 mg/kg BW respectively. Rats were sacrificed 8, 16 and 24 weeks post- AOM administration. Aberrant crypt foci (ACF) were analyzed. Tumor foci were characterized by gross examination and histopathological characteristics.</p><p> </p><p><strong>Results:</strong> All rats in the AOM groups developed tumors in the colonic mucosa. Formation of ACF was detected starting from 8 weeks post-AOM injection. The highest number of ACF with multiple crypts was observed at 16 weeks post-AOM administration. The total number of ACF did not vary between the two AOM doses. Mild, moderate and severe dysplastic cells were observed in colonic mucosa starting 8 weeks post-AOM injection. There was no statistically significant difference between number of severe dysplastic cells between the two AOM doses.</p><p> </p><p><strong>Conclusion:</strong> Administration of AOM 15 mg/kg BW SC is able to induce CRC in male Wistar rats. Higher dose is not necessary since it does not result in higher tumor incidence. This cancer model may be utilized to study chemopreventive effect of various agents in the future.</p></div>

Ethyl acetate fraction of Muntingia calabura L. exerts anti-colorectal cancer potential via regulating apoptotic and inflammatory pathways

Ethnopharmacological relevanceMuntingia calabura L. is a plant with traditional pharmacological relevance. The various plant parts are used by tribal communities for treating gastric ulcers, prostate gland swellings, headache, cold etc. Hence, an attempt was made to evaluate the anti-colorectal cancer potential of ethyl acetate fraction of M. calabura (EFMC). Materials and methodsHR LC-MS analysis was carried out for the identification of compounds present in EFMC. 1,2 Dimethylhydrazine (DMH) induced animal model was used for the evaluation of anti-CRC potential of EFMC. Antioxidant enzyme status, oxidative stress marker status, hepatic and renal function marker level were determined. Evaluation of mRNA level expression of inflammatory and apoptotic genes, hematological and histopathological examinations were also carried out to figure out the extent of colorectal cancer (CRC) and the beneficial role offered by EFMC. ResultsHR LC-MS analysis of EFMC revealed the presence of ten pharmacologically active compounds. EFMC treatment made the altered levels of antioxidant enzymes, oxidative stress markers, liver and renal function markers to retain near to its normal range. The hematological and histopathological evaluations also confirmed the anti-CRC effects exhibited by EFMC. EFMC offered a regulatory control over the inflammatory and apoptotic genes thereby mitigating the damaging effects of CRC. ConclusionThe present study depicted the presence of therapeutically active compounds exhibiting strong antioxidant, anti-inflammatory and anticancer potential. The beneficial role offered by these compounds could be responsible for the amelioration of DMH induced CRC. Hence, EFMC can be used as an anti-CRC agent in human subjects.

Hepatoprotective effect of Matricaria chamomilla aqueous extract against 1,2-Dimethylhydrazine-induced carcinogenic hepatic damage in mice

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.

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUNDEpigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC.AIMTo understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.METHODSDMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG.RESULTSAt week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively.CONCLUSIONEGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

The Effect of Aqueous Extract of Ocimum gratissium (Linn) on 1, 2 - Dimethyl Hydrazine induced Colon Cancer in Male Wistar Rats

Background Colon cancer is one of the leading causes of cancer death world-wide. There is a steady increase in incidence over the past four decades in developing countries. This has been partly attributed to increasingly low intake of vegetables among other causes. Aims Therefore this study aims to evaluate the protective effect of aqueous extract of Ocimumgratissimum (OG) leaves (a staple vegetable) on experimental model of colon carcinogenesis induced with 1, 2 Dimethylhydrazine (DMH). This is compared with celecoxib (a cyclooxygenase-2 inhibitor) which is used in the chemoprevention of colon cancer. Methods Sixty adult male Wistar rats were randomly divided into six groups: A to F, n=10. Group A was the normal control, Group B was given only DMH weekly for 16 weeks,Groups C, D and E were given graded doses of OG for two weeks prior to cancer induction by DMH. After which both OG and DMH were given for 16weeks. Group F received celecoxib daily for two weeks prior to cancer induction. Colonic wall was analysed grossly, histologically and biochemically. The induced lesions were staged investigated and staged using Duke’s Staging method. Results The result showed tumour incidence in groups B and C while no evidence of primary colonic tumour was observed in groups A, D, E and F. There was a dose dependent increase in the goblet cell count in the groups treated with OG with group E being statistically higher than group F. There was a significant reduction in collagen staining intensity (F = 129.74, p < 0.0001) for the colonic wall in group B when compared to other groups. There was a decreased nucleo-cytoplasmic ratio in groups C, D, E and F when compared to group B. There was a significant increase in the concentration of nitric oxide and prostaglandin E2in group B when compared to other groups D, E and F. Conclusion In conclusion, this research showed a protective effect of Ocimumgratissimum leaves on 1, 2-dimethylhydrazine-induced colon cancer which further corroborated its ethno-medicinal use.

Additive-promoted hypergolic ignition of ionic liquid with hydrogen peroxide

The exploration of environmentally friendly hypergolic combinations of ionic liquid fuels and hydrogen peroxide as an oxidizer offers opportunities to replace commonly used conventional toxic, corrosive and carcinogenic hydrazine-based liquid hypergolic combinations. Various research opportunities await regarding the detailed investigations of green hypergolic ionic liquids (HILs) with rocket grade hydrogen peroxide (RGHP, >85% H2O2). In this work, the combustion of HILs 1-ethyl-3-methyl imidazolium cyanoborohydride ([EMIM][BH3CN]) and 1-allyl-3-ethyl imidazolium cyanoborohydride ([AEIM][BH3CN]), and HIL-additive mixtures with 95% H2O2 has been investigated. A new additive, 1,3-dimethyl imidazolium copper iodide ([diMIM]n[Cu2I3]n) was synthesized successfully; a structural investigation was performed through the use of single-crystal x-ray diffraction analysis through which a crystal density of 3.22 g/cm3 was revealed. The physicochemical properties (density, viscosity, and decomposition temperature) as well as performance parameters (ignition delay and specific impulse) of 2 to 15 wt% of [diMIM]n[Cu2I3]n in [EMIM][BH3CN] were determined. A 15 wt% of [diMIM]n[Cu2I3]n exhibited ignition delay time (IDT) values of 13 and 29 ms under fuel-rich and oxidizer-rich conditions, respectively; these IDT values are 100 times lower than those for [EMIM][BH3CN]. Interestingly, [diMIM]n[Cu2I3]n-[EMIM][BH3CN] combinations revealed high density (>0.98 g/cm3), good thermal (>200 °C) and chemical stability, and 5.6–6.0% higher density specific impulse than those found for unsymmetrical dimethyl hydrazine. The additive-promoted hypergolic combustion of HIL with RGHP opens a new avenue to the replacement of conventional toxic hypergolic combinations.

Research Progress on Detection Methods of Trace Dimethyl Hydrazine

UDMH is an important fuel for missiles, satellites and spacecraft launch tests and carrier rockets. It is still very difficult to detect trace UDMH in environmental samples. The research status of gas chromatography (GC), high performance liquid chromatography (HPLC), ion chromatography (IC) and other techniques applied to the analysis of trace UDMH is reviewed. The advantages and disadvantages of these methods are discussed.

Major products and their formation and transformation mechanism through degrading UDMH wastewater via DBD low temperature plasma

ABSTRACT Unsymmetrical dimethylhydrazine (UDMH) is a liquid propellant widely used in aviation and aerospace. It produces a large amount of dimethyl hydrazine wastewater during long-term storage, testing, and reinjection. Traditional treatments produce numerous secondary contaminants such as residual high carcinogens, including N-nitrosodimethylamine (NDMA) and formaldehyde dimethylhydrazone (FDMH). In this paper, the dielectric barrier discharge (DBD) low temperature plasma technology is used to degrade the dimethyl hydrazine wastewater. Aiming at the problem of secondary pollutants in the degradation process, we used qualitative and quantitative methods to study the changes of NDMA and FDMH during the degradation of dimethyl hydrazine wastewater by DBD low temperature plasma. The kinetics of these two products showed that the degradation process of NDMA was consistent with the first-order reaction kinetics. Using density functional theory, we established molecular models of UDMH, NDMA and FDMH. According to the molecular orbital theory, the formation mechanism of NDMA and FDMH was calculated from three aspects: reaction structure, reaction path and energy change. We found that during the degradation of dimethyl hydrazine, the dimethyl hydrazine oxidation product was initiated by hydrogen abstraction on methyl (-CH3) and amine (-NH2). NDMA is produced by the oxidation of -NH2, whereas FDMH is mainly produced from dimethyl hydrazine and formaldehyde.

High Fat High Calories Diet (HFD) Increase Gut Susceptibility to Carcinogens by Altering the Gut Microbial Community.

Objective: To investigate the risk of colorectal cancer and its relationship with colonic flora and microenvironment under high-fat and high-calorie diet. Methods: Wistar rats were used to study, and they were given normal diet, high-fat diet, and dimethyl hydrazine (DMH) to induce the occurrence of colorectal cancer. Then observe the difference in tumor formation and the relationship among microbial community, inflammatory factors and metabolism. Results: No tumors were found in the normal diet group (G1) and the high-fat diet group (G3). Four nodules were found in the four rats in the normal diet + DMH group (G2) and 8 cancerous nodules were formed in 7 rats (70%) from high-fat diet + DMH group (G4). Cholesterol and TNF-α increased, IL-1, IL-6 and LEP decreased in the high-fat diet group. The difference was statistically significant. In the cancer-inducing group, only the difference in cholesterol was statistically significant. Compared with the normal diet group (G1) and the high-fat diet group (G3), the rat's gut bacterial abundance was not significantly different, but the gut flora structure was significantly changed. The content of Candida in the intestinal tract of rats in the high-fat diet group was reduced (P = 0.015), while the content of Verrucomicrobia increased (P = 0.035); In the comparison of genus content, Ruminococcus, Candida, Saccharibacteria genera incertae sedis, Enterobacter, Clostridium IV, Enterococcus, Enterorhabdus, Acetivibrio, Adlercreutzia, Lactococcus, etc., decreased significantly, while Akkermansia, Warthococcus, Staphylococcus, Butyricimonas, Clostridium XVIII, etc. increased significantly.Conclusion: This study found that high-fat, high-calorie diet can increase the susceptibility of the intestine to carcinogenic factors. The reason may be that the high-fat diet causes the body to appear inflammatory states and microbial community imbalance, especially rumenococcus, candida, Saccharomyces, Enterobacter, Clostridium IV, Enterococcus, Enterobacter, Vibrioaceticus and other genus reduction are important links. Exploring ways to improve these floras is an important factor to improve the resistance of the intestinal tract to cancer-inducing agents.

In vitro and In vivo Evaluation of Anticancer Properties of Clerodendrum indicum (L.) Kuntze in Colon Cancer

Cancer has become a global burden currently. Although various treatment options exist today, there is still an urgent need for screening newer drugs owing to the fact that the chemotherapeutic agents have a huge and debilitating side effect profile and a risk of resistance to the existing drugs. The present study was aimed at evaluating the anticancer properties of Clerodendrum indicum both in vitro and in vivo. Root extract of the plant was prepared by soxhlet extraction method using ethanol after overnight maceration and then partitioned with petroleum ether (PEF) and ethyl acetate (EAF). Total flavonoid content was estimated in the fractions using quercetin as standard followed by HPLC characterization. PEF contained 300.37μg and EAF contained 235.14μg flavonoid equivalent to quercetin per mg of fraction. MTT assay was performed to evaluate the in vitro antiproliferative activity and the IC50 values of EAF and PEF were found to be 72.83μg/ml and 31.33μg/ml respectively on HCT116 cell line. Apoptotic index was calculated to check the mode of cell death in the treated groups and the PEF fraction showed significant apoptotic index. Cell cycle analysis was carried out using flow cytometer to check the cell cycle specificity and the inhibition was specific to G2/M phase. Dimethyl hydrazine induced in vivo model of colon cancer was used to investigate the activity of the fractions in vivo on male Wistar rats. The fractions showed no significant change in the hematological parameters. The study showed that the fractions exhibited cytotoxic properties both in vitro and in vivo

Хемилюминесцентный метод определения несимметричного диметилгидразина в водных объектах

Для оперативного контроля качества водных сред предложен хемилюминесцентный метод количественного определения несимметричного диметилгидразина (НДМГ) в водных объектах. В основе метода анализа НДМГ лежит определение расхода окислителя на нейтрализацию исследуемого вещества. В качестве окислителя использован перманганат калия, подкисленный концентрированной серной кислотой до рН = 1-2. На первом этапе перманганат калия реагирует с НДМГ, далее количество непрореагировавшего окислителя измеряется в ходе его реакции с люминолом методом хемилюминесценции. По результатам изменения интенсивности излучения света в реакции хемилюминесценции определяется концентрация окислителя в реакционной смеси, что позволяет количественно определить содержание НДМГ в пробе. Концентрацию НДМГ определяют по максимальной интенсивности свечения в системе люминол - подкисленный перманганат калия. Показано, что предлагаемый метод превосходит по точности измерений традиционный фотоколориметрический метод определения НДМГ. При этом хемилюминесцентная реакция позволяет значительно сократить продолжительность снятия показаний и ускорить обработку данных (продолжительность измерений не превышает 2,5 мин), т.е. обеспечить экспресс-анализ НДМГ в растворах в полевых условиях и в мобильных лабораториях. A chemiluminescence mediated procedure for quantitative determination of unsymmetrical dimethyl hydrazine (UDMH) in water bodies is proposed which can be applied for prompt quality control of aqueous media. The UDMH analysis is based on determining an oxidizing agent uptake required for neutralization of the analyzed compound. Potassium permanganate acidified with concentrated sulfuric acid for pH value adjustment up to 1-2 is used as the oxidizing agent. The first step of the procedure involves interaction of potassium permanganate with UDMH followed by chemiluminescence reaction of unreacted oxidant residues with luminol. Measurements of changes in the intensity of light emission in the chemiluminescence reaction are performed for determination of concentration of the oxidizing agent in the reaction mixture, which provides quantitative determination of UDMH content in the sample. The concentration of UDMH is calculated from maximum luminous intensity in the luminol - acidified potassium permanganate system. The proposed method has demonstrated a superior accuracy as compared to the traditional photocolorimetric method for determining UDMH. Moreover, the chemiluminescent reaction allows to reduce significantly the duration of the analytical procedure and accelerates the data processing (the average time of measurement does not exceed 2.5 minutes), i.e. provides express-analysis of UDMH in aqueous solutions, in particular, in the field conditions and mobile laboratories.

WATER MEDIATED ONE-POT, FOUR COMPONENT SYNTHESIS OF 3,3-DIMETHYL-13-ARYL-3,4-DIHYDRO-1H-INDAZOLO[1,2-b]PHTHALAZINE-1,6,11(2H,13H)-TRIONES

Water mediated one-pot, four-component synthesis of substituted 2H-indazolo[2,1-b]phthalazine-triones from dimethyl phthalate, hydrazine, dimedone and aromatic aldehydes have been reported in the presence of p-toluenesulfonic acid (PTSA) as catalyst at 100 °C for 1.5-2.0 h. This methodology offers several advantages such as good yields, short reaction time, simple procedure, mild condition and environmentally begins.

Effect of Ranolazine on 1, 2 - Dimethyl hydrazine induced colon cancer in mice

Effect of Ranolazine on 1, 2 - Dimethyl hydrazine induced colon cancer in mice

Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO2)

The toxicity of dietary E 171, a food grade titanium dioxide was evaluated. A recent study reported rats receiving E 171 in water developed inflammation and aberrant crypt foci (ACF) in the gastrointestinal tract. Here, rats received food containing E 171 (7 or 100 days). The 100-day study included feeding E 171 after dimethylhydrazine (DMH) or vehicle only pretreatment. Food consumption was similar between treatment groups with maximum total cumulative E 171 exposure being 2617 mg/kg in 7 days and 29,400 mg/kg in 100 days. No differences were observed due to E 171 in the percentage of dendritic, CD4+ T or Treg cells within Peyer's patches or the periphery, or in cytokine production in plasma, sections of jejunum, and colon in 7- or 100-day E 171 alone fed rats. Differences were observed for IL-17A in colon (400 ppm E 171 + DMH) and IL-12p70 in plasma (40 ppm E 171 + DMH). E 171 had no effect on histopathologic evaluations of small and large intestines, liver, spleen, lungs, or testes, and no effects on ACF, goblet cell numbers, or colonic gland length. Dietary E 171 administration (7- or 100-day), even at high doses, produced no effect on the immune parameters or tissue morphology.

Ignition study of amine borane/cyanoborane based green hypergolic fuels

Boron based compounds have been looked upon as possible replacements to conventional toxic hypergolic fuels in propellant system. In an attempt to add to the pool of boron based hypergols, a series of new amine borane/ cyanoborane zwitterionic compounds were developed. Their hypergolic reactivity, performance parameters and physico-chemical properties were examined, in detail. The unsymmetrical dimethyl hydrazine (UDMH) based zwitterions, UDMH-borane and UDMH-bisborane displayed strikingly lower ignition delay times of 2.2 and 2 ms, respectively and high specific impulse 241 and 245 s, respectively. The pyridinium-cyanoborohydride exhibited high heat of formation (146 kJ/mol) than UDMH. While all the developed compounds exhibited higher density than the UDMH. Chemical stability of UDMH-borane was investigated at different environmental conditions; it was found to be stable for longer duration. Low ignition delay, good thermal and chemical stability, positive heat of formation, high specific impulse, ease of synthesis, and commercially available starting materials are the promising features of these compounds which make them attractive prospects in revolutionizing the area of green hypergolic fuel in liquid as well as hybrid rocket propulsion.

68Ga-Glutathione radio-complex as a new diagnostic probe for targeting colon cancer in rats.

Glutathione (GSH) plays an important role in a horde of cellular events that include cell proliferation and apoptosis.The present study describes the radio-synthesis and characterization of gallium-68 (68Ga)-labelled glutathione for its application in radionuclide imaging of cancer. The radio-synthesis of radio-complex 68Ga-GSH was performed by the direct labeling method. The developed radio-complex was subjected to quality control tests. Colon tumors were developed in healthy male Sprague Dawley (S.D) rats by giving subcutaneous injections of dimethylhydrazine (DMH) in order to monitor the uptake of 68Ga-GSH radio-complex. Gallium-68-labelled glutathione was synthesized with a labeling efficiency of 73.5%±1%. Percentage plasma protein binding and log Po/w values for the radio-complex were found to be 20%-30% and -0.223±0.12, respectively. A significantly higher percentage specific uptake value of newly developed 68Ga-GSH complex was observed in colon tumor in comparison to soft tissue at 90 minutes post administration thereby exhibiting specificity for cancerous cells, which was also witnessed significantly increased overtime from the ratio of colon tumor uptake to normal colon uptake (P≤0.05). Therefore, 68Ga-labelled glutathione can further be exploited for radionuclide imaging and assessment of tumor drug resistance in patients.

EFFECTS OF VIRGIN COCONUT OIL AND LAURIC ACID “WITH OR WITHOUT 5-FLUOROURACIL” ON DIMETHYLHYDRAZINE-INDUCED HEPATOTOXICITY IN MALE RATS

Dimethylhydrazine (DMH) is highly toxic for the different body organs, including the liver. The current study aimed to investigate the potential protective role of virgin coconut oil (VCO) and lauric acid (LA) in presence/absence of a chemotherapy drug “5-fluorouracil (5-FU)” against the hepatoxicity induced by DMH in male rats (Rattus norvegicus). Ninety rats were randomly divided into nine groups (n = 10). (G1) control group; (G2) rats received 4 mL VCO/kg body weight (b.wt) , orally/day after day for six weeks starting from week 13; (G3) rats received LA (200 mg/kg b.wt), orally/day after day for six weeks as in G2; (G4) rats were injected subcutaneously (s.c.) with DMH (20 mg/kg b.wt), once/week for the first six weeks; (G5) rats received DMH as in G4 and intraperitoneally (i.p.) injected with 5-FU (75 mg/kg b.wt), once/week starting from week 13 for three successive weeks; (G6) rats received DMH and VCO as in G4 and G2, respectively; (G7) rats received DMH and LA as in G4 and G3, respectively; (G8) rats received DMH, 5-FU, and VCO as in G4, G5, and G2, respectively; (G9) rats received DMH, 5-FU, and LA as in G4, G5, and G3, respectively. The results showed that DMH injection caused oxidative stress and histopathological alterations in the liver tissue, as well as dyslipidaemia. However, treatment of male rats with VCO or LA in presence/absence of 5-FU reduced significantly the DMH-induced hepatotoxicity.

Gradual Histopathologic Changes During Development of Colorectal Cancer

Background: Colorectal cancer is one of the most common causes of mortality in the world.Objectives: The aim of this study was to investigate the histopathologic changes including hyperchromatism, tissue lymphocyteinfiltrations (TILs), aberrant crypt foci (ACF), microvessel density (MVD), p53, Bcl-2 and CD31 changes during colorectal cancer development.Methods: Subcutaneous injections of dimethyl hydrazine DMH were administered to rats (40 mg/kg body weight) for 10 weeks.Rats were fed by food and water until 40th week and sacrificed two by two within 10, 15, 20, 25, 30 and 40 weeks after the start oftreatment. Thin paraffinized sections were applied to anti-CD31, anti-Bcl-2 and anti-p53 staining procedures. MVD and ACF werereported as mean value of three HPFs.Results: Hyperchromatism, TILs and angiogenesis were the most common initial histologic changes which started at 10th week ofDMH treatment. Hyperchromatism’s severity increased earlier than other changes and reached the highest value at the 25th week.The highest value of all variants occurred in the 40th week except the TILs which started to achieve the highest value in week 30 andincreased until 40th week. A diminished amount of p53 was observed at week 40, however, increased intensity of CD31 and Bcl-2were seen between 30th and 40th week.Conclusions: In conclusion, TILs and angiogenesis might be the important earliest factors contributing to colorectal cancer progression.

A CHEMICAL COMPOSITION OF SNOW ON AREAS EXPOSED TO SPACE-ROCKET ACTIVITIES POLLUTION (ALTAI REPUBLIC)

There are two areas in the Altai Republic where second rocket stages of launch vehicles fall down. They use unsymmetrical dimethyl hydrazine (UDMH) and nitrogen tetraoxide (N2O4) as a part of fuel. The snow possesses of the high sorbtion capability, low chemical and biological activity, and is the most informative object for the investigation of chemical effects on the environment by vehicle launchings. The article represents results of the investigation of the snow pollution carried out over the period of from 2011 to 2015. The chemical analysis of snow from the areas where second rocket stages of launch vehicles fell back to the Earth testify samples fail to contain UDMH and its most dangerous transformation product - NDMA. Published data of the atmospheric pollution modeling at launching space vehicles also admit the low probability of the surface contamination by falling second rocket stages of launching vehicles. The average concentration of nitrate ion, ammonium ion, pH level meets Environmental standards. The chemical composition of atmospheric fallout in the neighboring territory is mostly determined by operational features and proximity of anthropogenic objects. The amount of contaminants in atmospheric fallout declines with the distance from emission sources. Dust load to exploration territory does not exceed a background value for Siberian region being hundred times lower then such values for industrial and residential areas. Analysis of atmospheric flow movements and the wind rose in the winter in the Altai Mountains shows on the likely entry into the territory precipitation contaminated by acid-forming emissions of metallurgical enterprises of East Kazakhstan.