Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice.
BACKGROUND
There are about 600 million betel quid chewers in the world. Betal quid chewing is one of the major risk factors of hepatocarcinoma, oropharyngeal and esophagus cancers. Arecoline, the main Areca alkaloid of the betel nut is reported to have cytotoxic, genotoxic and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucosal fibrosis, leukoplakia and oral cancer, and has also been found to impose toxic manifestations in immune, hepatic and other defense systems of the recipient.


OBJECTIVE
The precise molecular mechanisms underlying the toxic effects of arecoline deserve investigation. To clarify the action of arecoline on defense systems, immune, hepatic and detoxification system were studied in mice.


METHODS
Cell count and cell cycle of the splenocytes were studied for evaluating cell immunity. Liver function test (LFT) was followed by assaying different enzyme systems from serum (SGPT, SGOT and ALP) and liver (GST for detoxication enzyme, SOD and catalase for antioxidant enzymes and GSH for non-enzymatic antioxidant) and by ultrastructural studies of hepatocytes.


RESULTS
Here we report that arecoline arrested splenic lymphocyte cell cycle at lower concentration with induced apoptosis at higher concentration thereby causing immunosuppression in arecoline recipients. Besides, it resulted in hepatotoxicity in arecoline recipient mice by disrupting the hepatocyte ultrastructure, as judged by liver ultrastructural studies that showed decreased nuclear size, RER with profusely inflated cysternae and abundance of lipid droplets, and by up regulating hepatotoxic marker enzymes (SGOT and SGPT) in serum. Arecoline also caused depression of antioxidants, i.e., superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione-S-transferase (GST) that are known to neutralize reactive oxygen species.


CONCLUSIONS
All these above-mentioned results led us to conclude that arecoline attacks multiple targets to finally generate systemic toxicity in mice.
Dasgupta
Romi
R
Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Calcutta 700 019, India.
Saha
Indraneel
I
Pal
Suman
S
Bhattacharyya
Arindam
A
Sa
Gaurisankar
G
Nag
Tapas C
TC
Das
Tania
T
Maiti
B R
BR
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001115:Arecoline / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000975:Antioxidants; D001115:Arecoline; D004247:DNA