<abstract xmlns="http://www.w3.org/1999/xhtml"><p><italic>N′</italic>-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 time-dependent 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&amp;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 (<italic>p</italic>&lt;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 &amp; 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) house-keeping, 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.</p></abstract>

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 time-dependent 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) house-keeping, 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.

Dose-dependent effect of <italic>N′</italic>-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

Biochemical and Clinical Genetics Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh-202002 (U.P), India

Interdisciplinary Toxicology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Dose-dependent effect of -Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

N′-Nitrosodiethylamine (NDEA) is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is...

Dose-dependent effect of N′-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

Published Online: Dec 10, 2015

Page range: 1 - 7

Received: Jul 03, 2014

Accepted: Oct 24, 2014

DOI: https://doi.org/10.1515/intox-2015-0001

Keywords
hepatotoxicity, -Nitrosodiethylamine, oxidative stress, polypeptide repertoire, RBC, SDS-PAGE

© 2015 Interdisciplinary Toxicology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Dose-dependent effect of N′-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

Published Online: Dec 10, 2015

Page range: 1 - 7

Received: Jul 03, 2014

Accepted: Oct 24, 2014

DOI: https://doi.org/10.1515/intox-2015-0001

Keywordshepatotoxicity, -Nitrosodiethylamine, oxidative stress, polypeptide repertoire, RBC, SDS-PAGE

© 2015 Interdisciplinary Toxicology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
hepatotoxicity, -Nitrosodiethylamine, oxidative stress, polypeptide repertoire, RBC, SDS-PAGE