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Experimental Colon Carcinogens and Their Mode of Action
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
John H. Weisburger, Emerich S. Fiala
Methylazoxymethanol induces primary colon cancer in most species in which it has been tested, although oral administration of MAM acetate to old-world monkeys caused hepatocellular carcinoma and intrahepatic bile carcinoma with some colon polyps.112 In guinea pigs, likewise, hepatocarcinomas and bile duct carcinomas were observed but no colon tumors were seen.8 MAM is the last step in the metabolic sequence of carcinogens based on 1,2-dimethylhydrazine, under which title this sequence, as well as the terminal activation step, was discussed (Figure 1). In essence, current views hold that the liver performs the early steps, and MAM is carried to the target organs via the blood. MAM is also excreted in the urine,12 but not in the feces (absence of compound and of mutagenicity). MAM is mutagenic and alkylates DNA, specifically guanylic acid at O6 and at N7.
Laterality in functional and metabolic state of the bulbectomised rat brain detected by ASL and 1H MRS: A pilot study
Published in The World Journal of Biological Psychiatry, 2023
Iveta Pavlova, Eva Drazanova, Lucie Kratka, Petra Amchova, Ondrej Macicek, Jana Starcukova, Zenon Starcuk, Jana Ruda-Kucerova
Regarding the lack of CBF differences between the OBX model and the control animals, our findings are supported by an earlier OBX model study (Gigliucci et al. 2014). However, this result contradicts the clinical data (Wang et al. 2014; Vasic et al. 2015; Li et al. 2018; Sheng et al. 2018; Cooper et al. 2020) as well as the results from the Wistar Kyoto rat model of depression (Gormley et al. 2016), reporting regional differences of the CBF between depression and control group. The clinical results are ambiguous, assessing various ununified brain regions. Lower CBF in the cortical regions was shown in MDD (Sheng et al. 2018) and the Wistar Kyoto depression model (Gormley et al. 2016) compared to the controls, which was not confirmed by our data. Hence, the OBX model may not be adequate to mimic clinically proven CBF alterations. The negative result seems convincing, given that we previously observed significant differences in regional CBF in a neurodevelopmental model of schizophrenia induced by prenatal exposure to methylazoxymethanol acetate with n = 6–8 rats per group (Drazanova et al. 2019). Furthermore, we reported both acute and chronic effects of olanzapine on regional CBF with n = 7 rats per group (Drazanova et al. 2019).
Glucocorticoid receptors participate in epilepsy in FCDII patients and MP model rats: A potential therapeutic target for epilepsy in patients with focal cortical dysplasia II (FCDII)
Published in Expert Opinion on Therapeutic Targets, 2022
Xiaoqing Zhang, Xiaolin Yang, Bing Chen, Kaifeng Shen, Guolong Liu, Zhongke Wang, Kaixuan Huang, Gang Zhu, Tingting Wang, Shengqing Lv, Chunqing Zhang, Hui Yang, Zhi Hou, Shiyong Liu
Pregnant rats were randomly divided into the control and methylazoxymethanol (MAM) groups. Neurons were isolated from postnatal day 0 (P0) offspring rats of control and MAM group (MAM group = 9 rats, control group = 9 rats) for primary neuronal culture. The remaining offspring were used for subsequent experiments. The offspring of control group were divided into the control and epilepsy groups. The offspring of MAM group were divided into the MAM and MAM)/pilocarpine (MP) groups. Rats in the epilepsy group and MP group were injected with pilocarpine 2 months after birth. After spontaneous recurrent seizure, rats were subjected to PCR, Western blotting, Nissl staining, immunohistochemistry, patch-clamp recording and EEG. The detail protocol is shown in Figure 1.
Methanolic Extract of Muntingia Calabura L. Mitigates 1,2-Dimethyl Hydrazine Induced Colon Carcinogenesis in Wistar Rats
Published in Nutrition and Cancer, 2021
Ninan Jisha, A. Vysakh, V. Vijeesh, P. S. Anand, M. S. Latha
1,2-Dimethyl hydrazine (DMH) is a colon specific carcinogen widely used in experimental animals to induce colorectal tumors (5). DMH induced CRC emanates from various molecular and histopathological alterations in the colonic epithelium like the development of aberrant crypt foci (ACF) and mucin depleted foci (MDF) (6). ACF and MDF are the preneoplastic leisions that may contribute to the progression of colonic epithelial transformation into colorectal carcinoma which are considered as the early biomarkers of CRC (7, 8). The DMH is metabolized initially in the liver and transported to colon as glucoronide conjugates via bile or blood (9, 10) and further degraded into azomethane. The azoxymethane generated from azomethane by the process of oxidation (N-oxidation) undergoes hydroxylation to form methylazoxymethanol (an unstable compound) which readily generates a highly reactive electrophilic methyl diazonium ion. This process causes the release of methyl free radicals meanwhile in the presence of metal ions, DMH causes the generation of hydroxyl radical or hydrogen peroxide which evokes oxidative stress as a result of the imbalance between the ROS and endogenous antioxidants (11, 12). Oxidative stress further progresses to inflammation which finally promotes CRC.