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Cannabidiol hydroxyquinone-induced apoptosis of splenocytes is mediated predominantly by thiol depletion.
Toxicol Lett. 2010 May 19; 195(1):68-74.TL

Abstract

Cannabidiol, the major nonpsychotropic phytocannabinoid, has been recently demonstrated to induce apoptosis in primary lymphocytes via an oxidative stress-dependent mechanism. Cannabidiol can be converted by microsomal enzymes to the hydroxyquinone metabolite HU-331 that forms adducts with glutathione. The present study tested the hypothesis that HU-331 could cause apoptosis via the depletion of thiols in splenocytes. Our results showed that HU-331 treatment significantly enhanced splenocyte apoptosis in a time- and concentration-dependent manner. Concordantly, a gradual diminishment in the cellular thiols and glutathione was detected in HU-331-treated splenocytes. The apoptosis and thiol diminishment induced by HU-331 were abrogated in the presence of thiol antioxidants, including N-acetyl-(L)-cysteine and N-(2-mercaptopropionyl) glycine, whereas the non-thiol antioxidants catalase and pyruvate were ineffective. In comparison, both thiol and non-thiol antioxidants were capable of attenuating H(2)O(2)-induced thiol diminishment and reactive oxygen species generation in splenocytes. Collectively, these results suggest that HU-331 might be an active metabolite of cannabidiol potentially contributing to the induction of apoptosis in splenocytes, and that the apoptosis is primarily mediated by the loss of cellular thiols.

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Authors+Show Affiliations

Wu HY
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1 Sec. 4 Roosevelt Road, Taipei, Taiwan, ROC.
Jan TR
No affiliation info available

MeSH

AnimalsApoptosisCannabidiolCaspase 8LymphocytesMaleMiceMice, Inbred BALB CSpleenSulfhydryl Compounds

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20184945

Citation

Wu, Hsin-Ying, and Tong-Rong Jan. "Cannabidiol Hydroxyquinone-induced Apoptosis of Splenocytes Is Mediated Predominantly By Thiol Depletion." Toxicology Letters, vol. 195, no. 1, 2010, pp. 68-74.
Wu HY, Jan TR. Cannabidiol hydroxyquinone-induced apoptosis of splenocytes is mediated predominantly by thiol depletion. Toxicol Lett. 2010;195(1):68-74.
Wu, H. Y., & Jan, T. R. (2010). Cannabidiol hydroxyquinone-induced apoptosis of splenocytes is mediated predominantly by thiol depletion. Toxicology Letters, 195(1), 68-74. https://doi.org/10.1016/j.toxlet.2010.02.012
Wu HY, Jan TR. Cannabidiol Hydroxyquinone-induced Apoptosis of Splenocytes Is Mediated Predominantly By Thiol Depletion. Toxicol Lett. 2010 May 19;195(1):68-74. PubMed PMID: 20184945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol hydroxyquinone-induced apoptosis of splenocytes is mediated predominantly by thiol depletion. AU - Wu,Hsin-Ying, AU - Jan,Tong-Rong, Y1 - 2010/02/23/ PY - 2009/09/18/received PY - 2010/02/12/revised PY - 2010/02/15/accepted PY - 2010/2/27/entrez PY - 2010/2/27/pubmed PY - 2010/5/5/medline SP - 68 EP - 74 JF - Toxicology letters JO - Toxicol Lett VL - 195 IS - 1 N2 - Cannabidiol, the major nonpsychotropic phytocannabinoid, has been recently demonstrated to induce apoptosis in primary lymphocytes via an oxidative stress-dependent mechanism. Cannabidiol can be converted by microsomal enzymes to the hydroxyquinone metabolite HU-331 that forms adducts with glutathione. The present study tested the hypothesis that HU-331 could cause apoptosis via the depletion of thiols in splenocytes. Our results showed that HU-331 treatment significantly enhanced splenocyte apoptosis in a time- and concentration-dependent manner. Concordantly, a gradual diminishment in the cellular thiols and glutathione was detected in HU-331-treated splenocytes. The apoptosis and thiol diminishment induced by HU-331 were abrogated in the presence of thiol antioxidants, including N-acetyl-(L)-cysteine and N-(2-mercaptopropionyl) glycine, whereas the non-thiol antioxidants catalase and pyruvate were ineffective. In comparison, both thiol and non-thiol antioxidants were capable of attenuating H(2)O(2)-induced thiol diminishment and reactive oxygen species generation in splenocytes. Collectively, these results suggest that HU-331 might be an active metabolite of cannabidiol potentially contributing to the induction of apoptosis in splenocytes, and that the apoptosis is primarily mediated by the loss of cellular thiols. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/20184945/Cannabidiol_hydroxyquinone_induced_apoptosis_of_splenocytes_is_mediated_predominantly_by_thiol_depletion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(10)00089-5 DB - PRIME DP - Unbound Medicine ER -