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991.
Mridula Sharma Hor Kuan Chan Charlie A. Lavilla Jr Mylene M. Uy Gabriele Ruth Anisah Froemming Patrick Nwabueze Okechukwu 《Fundamental & clinical pharmacology》2023,37(4):769-778
Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague–Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway. 相似文献
992.
Lydie Boussicault Anne-Sophie Hérard Noel Calingasan Fanny Petit Carole Malgorn Nicolas Merienne Caroline Jan Marie-Claude Gaillard Rodrigo Lerchundi Luis F Barros Carole Escartin Thierry Delzescaux Jean Mariani Philippe Hantraye M Flint Beal Emmanuel Brouillet Céline Véga Gilles Bonvento 《Journal of cerebral blood flow and metabolism》2014,34(9):1500-1510
Huntington''s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD. 相似文献
993.
Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1–7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4–7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R. 相似文献
994.
目的观察新生大鼠缺氧缺血性脑损伤(HIBD)后冷诱导RNA结合蛋白(CIRP)表达的变化情况。方法将40只7日龄新生SD大鼠随机分为假手术组和HIBD组,分别采用real-time PCR及免疫组织化学方法检测假手术组和HIBD后不同时间点(6、12、24和48h)CIRP在大鼠脑皮质与海马表达的变化。结果利用免疫组化和real-time PCR检测发现,大鼠脑皮质的CIRP蛋白和CIRP mRNA表达呈持续降低趋势,HIBD后6、12 h开始减少;24~48h下降更为明显。海马CIRP蛋白和CIRP mRNA表达则表现为6 h先升48h后降。结论CIRP参与了新生大鼠脑缺氧缺血的应激过程,可能与缺氧缺血性脑损伤后的脑水肿及神经元凋亡相关。 相似文献
995.
Asma Mahfoudh-Boussaid Kaouther Hadj Ayed Tka Mohamed Amine Zaouali Joan Roselló-Catafau 《Renal failure》2014,36(9):1436-1442
Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1α (HIF-1α) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60?min of warm renal ischemia followed by 120?min of reperfusion, or to intraperitoneal injection of TMZ (3?mg/kg) 30?min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845?±?13 vs. 1028?±?30?U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105?±?12 versus 31?±?11?μL/min/g kidney weight and 95?±?1 versus 68?±?5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33?±?0.01 vs. 0.59?±?0.03?nmol/mg of protein) and an increase in glutathione concentration (2.6?±?0.2 vs. 0.93?±?0.16?µg GSH/mg of protein), glutathione peroxidase (95?±?4 vs. 61?±?3?µg GSH/min/mg of protein), and superoxide dismutase (25?±?3 vs. 11?±?2?U/mg of protein) and catalase (91?±?12 vs. 38?±?9?μmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18?±?2 vs. 8?±?0.1?pomL/mg of protein), HIF-1α (333?±?48 vs. 177?±?14?µg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1α stabilization and HO-1 activation. 相似文献
996.
Eun Ho KIM Mi-Sook Kim Chul-Koo Cho Won-Gyun Jung Youn Kyoung Jeong Jae-Hoon Jeong 《Journal of radiation research》2014,55(3):432-442
The purpose of this study was to investigate the efficacy of metformin as a radiosensitizer for use in combination therapy for human hepatocellular carcinoma (HCC). Three human HCC cell lines (Huh7, HepG2, Hep3B) and a normal human hepatocyte cell line were treated with metformin alone or with radiation followed by metformin. In vitro tests were evaluated by clonogenic survival assay, FACS analysis, western blotting, immunofluorescence and comet assay. Metformin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, metformin abrogated G2/M arrest and increased the cell population in the sub-G1 phase and the ROS level, ultimately increasing HCC cellular apoptosis. Metformin inhibits the repair of DNA damage caused by radiation. The radiosensitizing effects of metformin are much higher in neutron (high LET)-irradiated cell lines than in γ (low LET)-irradiated cell lines. Metformin only had a moderate effect in normal hepatocytes. Metformin enhances the radiosensitivity of HCC, suggesting it may have clinical utility in combination cancer treatment with high-LET radiation. 相似文献
997.
Anju Rani Anuj Kumar Ankita Lal Manu Pant 《International journal of environmental health research》2014,24(4):378-399
Cadmium is a widespread toxic pollutant of occupational and environmental concern because of its diverse toxic effects: extremely protracted biological half-life (approximately 20–30 years in humans), low rate of excretion from the body and storage predominantly in soft tissues (primarily, liver and kidneys). It is an extremely toxic element of continuing concern because environmental levels have risen steadily due to continued worldwide anthropogenic mobilization. Cadmium is absorbed in significant quantities from cigarette smoke, food, water and air contamination and is known to have numerous undesirable effects in both humans and animals. Cadmium has a diversity of toxic effects including nephrotoxicity, carcinogenicity, teratogenicity and endocrine and reproductive toxicities. At the cellular level, cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Most important seems to be cadmium interaction with DNA repair mechanism, generation of reactive oxygen species and induction of apoptosis. In this article, we have reviewed recent developments and findings on cadmium toxicology. 相似文献
998.
Zuzana Magdolenova Andrew Collins Ashutosh Kumar Alok Dhawan Vicki Stone 《Nanotoxicology》2014,8(3):233-278
Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo. 相似文献
999.
Hsiao-Chi Chuang Hung-Tzu Juan Chun-Nung Chang Yuan-Horng Yan Tzu-Hsuen Yuan Jyh-Seng Wang 《Nanotoxicology》2014,8(6):593-604
Exposure to zinc oxide (ZnO) metal fumes is linked to adverse human health effects; however, the hazards of ZnO nanoparticles (ZnONPs) remain unclear. To determine pulmonary exposure to occupationally relevant ZnONPs cause cardiopulmonary injury, Sprague-Dawley rats were exposed to ZnONPs via intratracheal (IT) instillation and inhalation. The relationship between intrapulmonary zinc levels and pulmonary oxidative-inflammatory responses 72 h after ZnONP instillation was determined in bronchoalveolar lavage fluid (BALF). Instilled ZnONPs altered zinc balance and increased the levels of total cells, neutrophils, lactate dehydrogenase (LDH) and total protein in BALF and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in blood after 72 h. The ZnONPs accumulated predominantly in the lungs over 24 h, and trivial amounts of zinc were determined in the heart, liver, kidneys and blood. Furthermore, the inflammatory-oxidative responses induced by occupationally relevant levels of 1.1 and 4.9 mg/m3 of ZnONP inhalation for 2 weeks were determined in BALF and blood at 1, 7 and 30 days post-exposure. Histopathological examinations of the rat lungs and hearts were performed. Inhalation of ZnONP caused an inflammatory cytological profile. The total cell, neutrophil, LDH and total protein levels were acutely increased in the BALF, and there was an inflammatory pathology in the lungs. There were subchronic levels of white blood cells, granulocytes and 8-OHdG in the blood. Cardiac inflammation and the development of fibrosis were detected 7 days after exposure. Degeneration and necrosis of the myocardium were detected 30 days after exposure. The results demonstrate that ZnONPs cause cardiopulmonary impairments. These findings highlight the occupational health effects for ZnONP-exposed workers. 相似文献