Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice

Dasgupta, Romi; Saha, Indraneel; Pal, Suman; Bhattacharyya, Arindam; Sa, Gaurisankar; Nag, Tapas Chandra; Das, Tania; Maiti, B. R.

doi:10.1016/j.tox.2006.07.016

Cited by 76 publications

(57 citation statements)

References 51 publications

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“…It is known that thiol depletion as well as ROS attack should be mainly responsible for arecoline-induced hepatoxicity (Dasgupta et al, 2006;Chang et al, 2001), and CYP enzymes play critical roles in mutagenic activation of the areca-specific N-nitrosamines (Miyazaki et al, 2005). The present work found that AH (4 and 20 mg/kg/d) significantly increased the hepatic CYP2E1 activity.…”

Section: Discussionsupporting

confidence: 52%

“…Arecoline ( Fig. 1), the main Areca alkaloid of the betel nut, is reported to have cytotoxic and genotoxic effects in non-liver cells (Kumpawat et al, 2003;Chou et al, 2009), hepatocytes (Kevekordes et al, 2001;Chou et al, 2008) and mice (Dasgupta et al, 2006), as well as hepatotoxicity and testicular toxicity in mice and rats in vivo (Dasgupta et al, 2006;Zhou et al, 2014). However, Cheng et al reported that arecoline induces the death of HA22T/VGH hepatoma cells, but not normal hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

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Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

et al. 2014

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-Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma. The aim of the present work was to evaluate the impact of arecoline on human hepatic cytochrome P450 (CYP) enzymes in vitro and rat hepatic CYP enzymes, as well as the hepatic oxidative stress and liver injury of rats in vivo. The in vitro results indicated that arecoline hydrobromide (AH) has no significant effect on the activities of CYP2B, 2C9, 3A4, 1A2, 2E1 and 2D6 in human liver microsome (HLM). However, oral administration of AH at 4 and 20 mg/kg/d for seven consecutive days significantly increased the activities of rat hepatic CYP2B, 2E1, 2D, 3A, 2C and 1A2. In addition, AH at 100 mg/kg/d significantly increased the levels of ALT, AST and MDA, decreased the levels of SOD, CAT, GSH-Px and GSH, in rat liver. The in vivo induction of AH on rat hepatic CYP isoforms suggested that the high risk of metabolic interaction should be existed when the substrate drugs of the six kinds of CYP isoforms was administered in betel-quid use human. Furthermore, the in vivo results also suggested that AH-induced hepatoxicity should be associated with the induction of AH on rat hepatic CYP2E1 and 2B.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

et al. 2014

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“…Arecoline, the major alkaloid of BN, has been reported to cause disruptions in hepatocyte ultrastructure in mice, including profuse inflation of the RER cisternae (Dasgupta et al, 2006). Arecoline has also been reported to cause suppression of the activity of the pineal gland in rats by inducing various ultrastructural alterations, such as dilation of the cisternae of the RER (Saha et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…5a-5c) in comparison with the chronically exposed P generation mice. It is, thus, likely that the observed aberration in RER structure induced by AEBN-exposure is mediated by arecoline (Dasgupta et al, 2006;Saha et al, 2007). This disruption of normal RER structure may be one of the factors contributing toward the detrimental effect of AEBN on mice.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural alterations in liver of mice exposed chronically and transgenerationally to aqueous extract of betel nut: Implications in betel nut‐induced carcinogenesis

Choudhury

Sharan

2009

Microscopy Res & Technique

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The aqueous extract of betel nut (AEBN) induces the formation of preneoplastic nodules in the liver of Swiss Albino mice and leads to increased predisposition to cancer when administered transgenerationally. The aim of this investigation was to elucidate the alterations in ultrastructure of subcellular organelles in the liver nodules using transmission electron microscopy and to determine whether these alterations have implications in AEBN-induced carcinogenesis. Male and female Swiss Albino mice were exposed to AEBN chronically and transgenerationally at a dose of 2 mg/mL in drinking water for 24 weeks. Extensive polymorphism was noted in nuclear shape and heterochromatin organization. Heterochromatin aggregation and marginalization were observed in the nuclei of chronically exposed mice, whereas transgenerationally exposed mice exhibited dispersion or loss of heterochromatin. The nuclear envelope was disrupted, and the nucleoli were enlarged in chronically exposed mice, whereas in transgenerationally exposed mice the nucleoli were reduced in size or totally absent. The cisternae of the rough endoplasmic reticulum were dilated and disrupted, and a large number of autophagic vesicles were observed in both chronically and transgenerationally exposed mice. Atypical mitochondria that underwent extensive cristolysis and progressively declined in size and number from the chronically exposed mice to the different generations of transgenerationally exposed mice were also observed. Thus, exposure to AEBN resulted in severe loss of ultrastructural integrity of cells in the liver nodules, and the progressive loss of mitochondrial function appeared to play a significant role in increasing the predisposition to cancer of mice exposed transgenerationally to AEBN.

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“…Jeng et al (2003) demonstrated that arecoline can regulate inflammatory processes by releasing cytokines including prostaglandin E2, interleukin-6 and TNF-a in primary oral gingival keratinocyte and KB carcinoma cells. Moreover, it can also regulate immunological functions and shows immunosuppression via inducing apoptosis of lymphocytes in vivo (Dasgupta et al 2006;Saha et al 2007). Arecoline-treated embryos exhibited general developmental retardation.…”

Section: Toxicologymentioning

confidence: 99%

The pharmacology, toxicology and potential applications of arecoline: a review

Liu

Peng

et al. 2016

Pharmaceutical Biology

114

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Context: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases. Objective: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future. Methods: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc. Results: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What's more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity. Conclusion: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug. ARTICLE HISTORY

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Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice

Cited by 76 publications

References 51 publications

Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

Ultrastructural alterations in liver of mice exposed chronically and transgenerationally to aqueous extract of betel nut: Implications in betel nut‐induced carcinogenesis

The pharmacology, toxicology and potential applications of arecoline: a review

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