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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.

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Resveratrol is a polyphenolic phytoalexin with numerous health benefits including fat reducing ability as well as anti‐proliferative and pro‐apoptotic properties. It is found in fruits such as raspberry, strawberry, and grapes. Considering nutritional importance of Resveratrol, this study was undertaken to investigate its hepatoprotective effect against Nitrosodiethylamine (NDEA)‐induced liver injury in rats. Resveratrol was administered to NDEA‐intoxicated rats for 2 weeks. Hepato‐somatic Index (HSI), Aspartate Transaminase (AST), Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), Lipid peroxides (LPO), Superoxide Dismutase (SOD), glycogen, and Na+/K+, Ca2+, Mg2+ ATPase activities were determined. Alteration in the liver anatomy was monitored by Haematoxylin and Eosin and Masson’s Trichrome stainings. Cycloxygenase‐2 (COX‐2) activity was assessed by Immunohistochemistry and Western blotting. Resveratrol restitutes the NDEA‐induced decline in HSI, glycogen, SOD, ATPases, and coincidental increase in AST, ALT, ALP, and LPO. Resveratrol refurbishes architectural changes, reduces collagen amassing and COX‐2 positive cells in the liver. This study reveals that Resveratrol offers hepatoprotection against NDEA‐induced injury through its anti‐inflammatory action and declining COX‐2 expression. Practical applications Despite various documented roles of Resveratrol, there is still a paucity of literature supporting its hepatoprotective role. The growing prevalence of liver diseases has witnessed a surge of interest in medicinally important botanicals wherein hepatoprotective active ingredients can be identified. Although herbal medication is preferred over synthetic pharmaceuticals because of their inherent efficacy and negligible side‐effects, identification and mode of action of active ingredients requires compatible attention. This study is the first that reveals anti‐inflammatory potential of Resveratrol, exerted via declining COX‐2 that offers hepatoprotection against NDEA‐induced liver fibrosis. These findings suggest Resveratrol as a potential anti‐fibrotic agent and the COX‐2 as a prospective target for drug discovery.

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