Effect of N'-nitrosodimethylamine on red blood cell rheology and proteomic profiles of brain in male albino rats (original) (raw)
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Interdisciplinary Toxicology, 2015
N'-Nitrosodiethylamine (NDEA) is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is an extensively used experimental model. In the present study, we analysed the dose-and timedependent effect of NDEA on hepatic damage, RBC rheology and proteomic profile in male Wistar rats. The rats, 5-6 weeks old, were divided into four groups: Group-1 served as control and received normal saline, Group-2 received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p.) and the animals were sacrificed after one week; the rats of Group-3 received a single dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4 received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed. Various biochemical parameters such as ALT, AST, ALP and bilirubin were determined. Further, RBC rheology, histopathology (H&E staining) of liver biopsies and polypeptide profiling (SDS-PAGE) in sera and liver sections were also carried out both in control and NDEA treated groups. Our results showed a significant increase in all the biochemical parameters of the liver function test (p<0.05). In NDEA treated categories dacryocytes (tear drop cells), schistocytes (fragmented cells), codocytes (target cells), acanthocytes (spur cells) and ovalocytes (oval cells) were observed. H & E stained liver biopsies treated with NDEA showed abnormal liver architecture with severe haemorrhage, neutrophilic infiltration and dysplastic hepatocytes manifested in a dose-dependent manner. Software analysis of SDS-PAGE of control and NDEA treated rat sera and liver revealed qualitative and quantitative differences in polypeptide composition. Based on the presence/absence, polypeptides were classified in three different categories: (1) housekeeping , present in all the groups investigated; (2) novel, present in either control or NDEA treated group at any given time; (3) differential expression, showing quantitative differences. Our study indicates a dose and time-dependent hepatocellular damage and proteome profile which is likely due to NDEA-mediated oxidative stress in rats.
Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats
Indian journal of experimental biology, 2000
Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The result...
The Effect Of N-Nitrosodimethylamine On Enzyme Activities And Histology In The Mouse
1999
who graced the weekly tea meetings with their, amongst other qualities, wit and humour. So much has been gained fr om listening to, and even more so participating in, their intellectual discussions. I am much indebted to Dr. Fauziah Othman fo r the use of histology fa cilities and also her help, advice and guidance in histology analysis, and also to Pn Safiah lalal for her kindness and help in handling histokinette machine. I owe a special debt of thanks to Mr. leeven all Karuppan, En. Ibrahim Yunus and all the other staff members of this Department, who have showed great patience and selflessness in helping me to settle in during the initial stage. I am very grateful to all my family fo r their continued moral support in pursuing my dreams. This work may not have materialised without the understanding and love, fr om my wife Dr. Norashikin Shamsudin. Last but not least, to my boy, Alif Farhan fo r the incredible joy, gift and privilege, he gives to me while I'm writing my thesis. I would like to dedicate this master's thesis to them ... .
The aim of this study is to review a procarcinogen, the N-Nitrosodimethylamine (NDMA), liver and kidney functional enzymes (in assessing action of toxicants such as NDMA) as well as oxidative stress parameters (in assessing the extent of free radical damage and scavenging). Catalase and hydro peroxidase enzymes convert hydrogen peroxide and hydro peroxides to non-radical forms and functions as natural antioxidant in human body. Enzymes like Superoxide Dismutase (SOD) and Catalase (CAT) and compounds such as tocopherol and ascorbic acid can protect organisms against free radical damage. Lipid peroxidation is a mechanism generally recognized as being the most important in the pathogenesis of liver injury by a number of toxic compounds including NDMA.
Assessment of biomarkers in acrylamide-induced neurotoxicity and brain histopathology in rat
Journal of Applied Biology & Biotechnology, 2018
The effects of acrylamide (ACR), a synthetic neurotoxic chemical compound on non-enzymatic and enzymatic stress markers and brain histopathology, were studied in Wistar rats. ACR (50 mg/300 ml) was ingested through drinking water on alternative days, and brain tissues were collected on the 13 th and 27 th days post-ingestion for analysis. Results revealed that ACR causes significant increase in non-enzymatic stress markers such as lipid peroxidation (P < 0.05) and nitric oxide (P < 0.05), but depletion of glutathione (P < 0.05). Enzymatic stress markers, glutathione peroxidase, and glutathione s-transferase activities significantly increased (P < 0.05) at the 13 th day post-ingestion, but decreased at the 27 th day. However, acetylcholine esterase activity dropped significantly (P < 0.05) at the 13 th and 27 th days post-ingestion. In addition, ACR induced histological changes in brain such as degeneration of pyramidal and glial cells, mild vacuolation of pyramidal cells, and spongiosis in glia cells on 13 th day post-ingestion. On the 27 th day, brain tissue necrosis and pyknosis, necrosis of neurons and neurophagia, focal gliosis, and demyelination of nerve fibers were observed. In conclusion, ACR influences non-enzymatic and enzymatic stress markers in brain tissue and induces neurodegeneration in Wistar rats.
2008
Succinic semialdehyde dehydrogenase (SSADH) deficiency and tyrosinemia type II are characterized by predominant tissue and blood accumulation of γhydroxybutyric acid (GHB) and tyrosine, respectively. Patients with SSADH deficiency and tyrosinemia type II present neurological signs and symptoms. Although mechanisms of brain damage remain unclear, they are probably related to the accumulation of GHB or tyrosine leading to possible noxious effects on central nervous system (CNS) development in those patients. Considering that the damaging consequences of oxidative stress have been implicated in a variety of disorders of CNS, the effect of GHB and L-tyrosine were investigated on some oxidative stress parameters in cerebral cortex homogenates of young rats. The in vitro and in vivo effects of GHB, or its precursor 1,4-butanediol (1,4-BD), were similar. It was observed that GHB or 1,4-BD impairs non-enzymatic antioxidant defenses and induces lipid peroxidation. On the other hand, the in vitro and in vivo effects of Ltyrosine were different. Oxidative damage to DNA was promoted while nonenzymatic and enzymatic antioxidant defenses, and thiol-disulfide redox state (SH/SS ratio) were markedly diminished by L-tyrosine in vitro. In contrast, the acute administration of L-tyrosine causes lipid peroxidation and protein oxidation, decreases non-enzymatic antioxidant defenses, alters SH/SS ratio and stimulates glucose-6-phosphate dehydrogenase activity. Taken together, it may be presumed that GHB and L-tyrosine elicit oxidative stress in cerebral cortex of young rats. If these effects also occur in the brain of patients affected by SSADH deficiency or tyrosinemia type II, it is possible that oxidative stress may contribute, at least in part, to the neurological dysfunction characteristic of these diseases.
Biochemical and histological alterations induced by fluid percussion brain injury in the rat
Brain Research, 1993
Background: Mosquito coil (MC) emits insecticide upon burning which provides limited protection against lethal mosquito borne diseases. However, apart from killing the insect, toxicities associated with the inhalation of these insecticides poses severe health hazards. However, the use of MC is increasing day by day in third world countries in particular but, yet to receive enough attention of both policy maker and general public. The current study was aimed to assess the MC smoke induced damage of pulmonary and hepatic tissues along with observing the alterations of several blood biochemical parameters in mice model. Methods: A total of twenty four Swiss albino mice were allowed to inhale the smoke of allethrin based MC at different duration per day for 120 days. By the end of treatment period, blood sample was drawn from each mouse and blood biochemical parameters including alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen(BUN), serum total protein, cholesterol, low density lipoprotein (LDL) and triglyceride (TG) were analyzed. Intact lung and liver were collected for histological analysis using standard protocol. Results: Biochemical study indicates elevated activity of two hepatic enzymes: ALT (89%), AST (85%), in comparison with the respective control. Increased level of some parameters of lipid profile including cholesterol (36%), LDL (48%) and triglyceride (30%) in smoke inhaled mice is the new finding of this study. On the contrary, the activity of serum total protein and BUN was decreased by 20% and 24%, respectively in inhaled mice. Pulmonary tissue of treated mice shows severe forms of emphysema and hyperplasia, especially in the peripheral region of lung, which is the hallmark of chronic obstructive pulmonary disease (COPD). Histological study of hepatic tissue shows apoptosis mediated damage of hepatocytes along with severe form of necrosis. Infiltration of Inflammatory cells was also observed in both of the organs. Conclusion: Results from the present studies suggest that chronic exposure of allethrin based MC is responsible factor for severe health complications such as COPD due to the alterations of the key biochemical parameters of blood and histo-organization of lung and liver.
Effects of N Ethyl N′ nitrosourea in mice brain in time fashion
INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES
Antioxidant enzyme plays a pivotal role in preventing oxidative stress. Chemical toxicants often exert adverse effects in the biological system by breaking the antioxidant response system leading to severe oxidative stress. N-Ethyl-N-Nitrosourea (ENU) is a DNA alkylating agent and is carcinogenic and neurotoxic in animals. ENU in the nervous system cause persistent alkylation of DNA within the neurons altering the normal functional activities of the brain. Prenatal exposure to ENU in rodents that generate malignant gliomas in the brain induces functional changes and apoptotic death in neuronal progenitors in the brain's subventricular zone (SVZ). However, as chemical toxicants, their role in the induction of oxidative stress in brain tissue and subsequent change in the brain were less studied. In this study, we have investigated the response antioxidant system and induction of oxidative stress in the Balb/c mice brain at various time points after ENU exposure. Exposures to ENU w...
European Journal of Pharmacology, 2000
Ž . CHP212 neuroblastoma cells were exposed to two different nitric oxide NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside. Apoptosis and necrosis were determined with flow cytometric analysis of annexin V binding and propodium iodide uptake. Both S-nitroso-N-acetylpenicillamine and sodium nitroprusside induced apoptosis, but with a different time dependency. Oxyhemoglobin Ž . NO scavenger attenuated the toxicity of S-nitroso-N-acetylpenicillamine, but had no effect on the toxicity of sodium nitroprusside. By Ž . contrast, deferoxamine iron chelator attenuated the toxicity of sodium nitroprusside, but had no effect on the toxicity of S-nitroso-N-Ž y . acetylpenicillamine. Urate ONOO scavenger did not influence the toxicity of either S-nitroso-N-acetylpenicillamine or sodium Ž y . nitroprusside, but protected from SIN-1 3-morpholinosydnonimine, ONOO donor . It was shown that both dithiothreitol and ascorbic acid affected the toxicity of S-nitroso-N-acetylpenicillamine and sodium nitroprusside in opposite ways. In the presence of dithiothreitol, superoxide dismutase and catalase decreased the toxicity of sodium nitroprusside. In the presence of cells, but not in their absence, S-nitroso-N-acetylpenicillamine decomposed with a half-life of about 4 h as assessed by the production of nitrite and absorbance reduction at 335 nm. Sodium nitroprusside decomposed very slowly in the presence of cells as assessed by the production of ferrocyanide.