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Investigating the Efficacy of Cannabidiol Against Arsenic-Induced Liver Cell Damage

Year 2025, Volume: 46 Issue: 1, 55 - 61, 25.03.2025

Serkan Şahin , Vugar Ali Türksoy , Serap Yalcin

https://doi.org/10.17776/csj.1616411

Abstract

Arsenic (As) exposure is known to have harmful effects, prompting the search for effective countermeasures. This study investigated the protective effects of cannabidiol (CBD) against arsenic toxicity in liver cell cultures (THLE-2). The IC50 values for As were determined, finding 10 µM in 2D and 15 µM in 3D cell lines. To assess CBD's protective efficacy, 5 µM of CBD was administered alongside arsenic at its IC50 concentration. The levels of oxidative stress markers, including Glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and catalase (CAT), as well as inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were measured using ELISA kits. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was conducted to evaluate As uptake in the cells. The results showed that CBD significantly enhanced cell proliferation and reversed the oxidative stress and inflammatory responses induced by arsenic exposure. Furthermore, CBD effectively reduced arsenic uptake into the cells. These findings provide compelling evidence for CBD's protective role against arsenic-induced toxicity, highlighting its potential as a therapeutic agent in mitigating the harmful effects of arsenic

Keywords

Arsenic Cannabidiol Toxicity THLE-2 ICP-MS

Ethical Statement

Ethical approval is not required as this is a cell culture study.

Supporting Institution

Yozgat Bozok University Scientific Research Projects Unit

Project Number

6608-TF/21-475

Thanks

This study is supported by Yozgat Bozok University Scientific Research Projects Unit (Project number: 6608-TF/21-475).

References

  • [1] Ishiguro S., Industries Using Arsenic and Arsenic Compounds, Appl. Organomet. Chem., 6 (4) (1992) 323–331.
  • [2] Zhao D., Yi H., Sang N., Arsenic Intake-Induced Gastric Toxicity Is Blocked by Grape Skin Extract by Modulating Inflammation and Oxidative Stress in a Mouse Model, Ecotoxicol. Environ. Saf., 233 (2022) 113305.
  • [3] Liu P., Xue Y., Zheng B., Liang Y., Zhang J., Shi J., Chu X., Han X., Chu L. Crocetin Attenuates the Oxidative Stress, Inflammation and Apoptosisin Arsenic Trioxide-Induced Nephrotoxic Rats: Implication of PI3K/AKT Pathway, Int. Immunopharmacol., 88 (2020) 06959.
  • [4] Mazumder D.N.G., Haque R., Ghosh N., De B.K., Santra A., Chakraborty D., Smith A.H. Arsenic Levels in Drinking Water and the Prevalence of Skin Lesions in West Bengal, India, Int. J. Epidemiol., 27 (5) (1998) 871–877.
  • [5] Abernathy C.O., Liu Y.P., Longfellow D., Aposhian H.V., Beck B., Fowler B., Goyer R., Menzer R., Rossman T., Thompson C., Arsenic: Health Effects, Mechanisms of Actions, and Research Issues, Environ. Health Perspect., 107 (7) (1999) 593–597.
  • [6] Santra A., Gupta J., Das De B.K., Roy B., Mazumder D.N.G. Hepatic Manifestations in Chronic Arsenic Toxicity, Indian J. Gastroenterol., 18 (1999) 152–155.
  • [7] Nevens F., Staessen D., Sciot R., Van Damme B., Desmet V., Fevery J., De Groote J., Van Steenbergen W. Clinical Aspects of Incomplete Septal Cirrhosis in Comparison with Macronodular Cirrhosis, Gastroenterology, 106 (2) (1994) 459–463.
  • [8] Rahman M., Tondel M., Ahmad S.A., Chowdhury I.A., Faruquee M.H., Axelson O. Hypertension and Arsenic Exposure in Bangladesh, Hypertension, 33 (1) (1999) 74–78.
  • [9] Benowitz N.L. Cardiotoxicity in the Workplace, Occup. Med., 7 (3) (1992) 465–478.
  • [10] Goldsmith S., Arthur H.L., Arsenic-Induced Atypical Ventricular Tachycardia, N. Engl. J. Med., 303 (19) (1980) 1096–1098.
  • [11] Schenk V.W., Stolk P.J., Psychosis Following Arsenic (Possibly Thallium) Poisoning, Psychiatr. Neurol. Nurochirurgia, 70 (1) (1967) 31–37.
  • [12] Guo H.R., Chiang H.S., Hu H., Lipsitz S.R., Monson R.R., Arsenic in Drinking Water and Incidence of Urinary Cancers, Epidemiology, 8 (5) (1997) 545–550.
  • [13] Rahman M., Tondel M., Ahmad S.A., Axelson O., Diabetes Mellitus Associated with Arsenic Exposure in Bangladesh, Am. J. Epidemiol., 148 (2) (1998) 198–203.
  • [14] Zhai Q., Narbad A., Chen W., Dietary Strategies for the Treatment of Cadmium and Lead Toxicity, Nutrients, 7 (1) (2015) 552–571.
  • [15] Gupta R., Flora S.J.S., Therapeutic Value of Hippophae Rhamnoides L. against Subchronic Arsenic Toxicity in Mice, J. Med. Food, 8 (3) (2005) 353–361.
  • [16] Nurchi V.M., Djordjevic A.B., Crisponi G., Alexander J., Bjørklund G., Aaseth J., Arsenic Toxicity: Molecular Targets and Therapeutic Agents, Biomolecules, 10 (2) (2020) 235.
  • [17] Jarjou’i A., Izbicki G., Medical Cannabis in Asthmatic Patients, Isr. Med. Assoc. J., 22 (4) (2020) 232–235.
  • [18] Booz G.W., Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress, Free Radic. Biol. Med., 51 (5) (2011) 1054–1061.
  • [19] Şahin S., Azarkan S.Y., Türksoy V.A., Evaluation of the Effect of Cannabidiol on the THLE-2 Liver Cell Line Exposed to Lead, Sci. Total Environ., 923 (2024) 170901.
  • [20] Styblo M., Razo L.M. Del Vega L., Germolec D.R., Lecluyse E.L., Hamilton G.A., Reed W., Wang C., Cullen W.R., Thomas D.J., Comparative Toxicity of Trivalent and Pentavalent Inorganic and Methylated Arsenicals in Rat and Human Cells, Arch Toxicol., 74 (2000) 289–299.
  • [21] Gęgotek A., Atalay S., Domingues P., Skrzydlewska E., The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts Following UVA or UVB Irradiation in 2D and 3D Cell Cultures, Cells, 8 (9) (2019) 995.
  • [22] Etienne de M., Fibre Hemp Cultivars: A Survey of Origin, Ancestry, Availabilityand Brief Agronomic Characteristics, J. Int. Hemp Assoc., 2 (1995) 67–73.
  • [23] Fitzcharles M., Clauw D.J., Hauser W.A., Cautious Hope for Cannabidiol (CBD) in Rheumatology Care, Arthritis Care Res. (Hoboken), 75 (6) (2023) 1371–1375.
  • [24] Niesink R.J.M., van Laar M.W., Does Cannabidiol Protect Against Adverse Psychological Effects of THC?, Front. psychiatry, 4 (2013) 130.
  • [25] Patel P.N., Pathak R., Rimonabant: A Novel Selective Cannabinoid-1 Receptor Antagonist for of Treatment Obesity, Am. J. Heal. Pharm., 64 (5) (2007) 481–489.
  • [26] Gelfand E.V., Cannon C.P., Rimonabant: A Selective Blocker of the Cannabinoid CB1 Receptors for the Management of Obesity, Smoking Cessation and Cardiometabolic Risk Factors, Expert Opin. Investig. Drugs, 15 (3) (2006) 307–315.
  • [27] Penner E.A., Buettner H., Mittleman M.A., The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults, Am. J. Med., 126 (7) (2013) 583–589.
  • [28] Weiss L., Zeira M., Reich S., Har-Noy M., Mechoulam R., Slavin S., Gallily R., Cannabidiol Lowers Incidence of Diabetes in Non-Obese Diabetic Mice, Autoimmunity, 39 (2) (2006) 143–151.
  • [29] Chen J., Hou C., Chen X., Wang D., Yang P., He X., Zhou J., Li H., Protective Effect of Cannabidiol on Hydrogen Peroxide‑induced Apoptosis, Inflammation and Oxidative Stress in Nucleus Pulposus Cells, Mol. Med. Rep., 14 (3) (2016) 2321–2327.
  • [30] Rajesh M., Mukhopadhyay P., Btkai S., Patel V., Saito K., Matsumoto S., Kashiwaya Y., Horvth B., Mukhopadhyay B.,

Arsenik neden olduğu karaciğer hücre hasarında karşı kannabidiolün etkinliğinin değerlendirlmesi

Year 2025, Volume: 46 Issue: 1, 55 - 61, 25.03.2025

Serkan Şahin , Vugar Ali Türksoy , Serap Yalcin

https://doi.org/10.17776/csj.1616411

Abstract

Arsenik (As) maruziyeti, zararlı etkileri bilinen bir durumdur ve etkili karşı önlemler arayışını teşvik etmektedir. Bu çalışmada, kannabidiolün (CBD) arsenik toksisitesine karşı karaciğer hücre kültürlerinde (THLE-2) koruyucu etkileri araştırılmıştır. As için IC50 değerleri belirlenmiş ve 2D hücre hatlarında 10 µM, 3D hücre hatlarında ise 15 µM bulunmuştur. CBD'nin koruyucu etkinliğini değerlendirmek amacıyla, IC50 konsantrasyonunda arsenik ile birlikte 5 µM CBD uygulanmıştır. Oksidatif stres belirteçleri olan GSH, MDA, MPO ve CAT seviyelerinin yanı sıra, inflamatuar sitokinler TNF-α, IL-1β ve IL-6, ELISA kitleri kullanılarak ölçülmüştür. As alımını değerlendirmek için ICP-MS analizi yapılmıştır. Sonuçlar, CBD'nin hücre proliferasyonunu önemli ölçüde artırdığını ve arsenik maruziyetiyle indüklenen oksidatif stres ve inflamatuar yanıtları tersine çevirdiğini göstermiştir. Ayrıca, CBD'nin arsenik alımını hücrelere etkili bir şekilde azalttığı tespit edilmiştir. Bu bulgular, CBD'nin arsenik kaynaklı toksisiteye karşı koruyucu rolünü güçlü bir şekilde desteklemekte ve arsenikin zararlı etkilerini hafifletmede terapötik ajan olarak potansiyelini vurgulamaktadır.

Keywords

Arsenik Kannabidiol Toksisite THLE-2 ICP-MS

Project Number

6608-TF/21-475

References

  • [1] Ishiguro S., Industries Using Arsenic and Arsenic Compounds, Appl. Organomet. Chem., 6 (4) (1992) 323–331.
  • [2] Zhao D., Yi H., Sang N., Arsenic Intake-Induced Gastric Toxicity Is Blocked by Grape Skin Extract by Modulating Inflammation and Oxidative Stress in a Mouse Model, Ecotoxicol. Environ. Saf., 233 (2022) 113305.
  • [3] Liu P., Xue Y., Zheng B., Liang Y., Zhang J., Shi J., Chu X., Han X., Chu L. Crocetin Attenuates the Oxidative Stress, Inflammation and Apoptosisin Arsenic Trioxide-Induced Nephrotoxic Rats: Implication of PI3K/AKT Pathway, Int. Immunopharmacol., 88 (2020) 06959.
  • [4] Mazumder D.N.G., Haque R., Ghosh N., De B.K., Santra A., Chakraborty D., Smith A.H. Arsenic Levels in Drinking Water and the Prevalence of Skin Lesions in West Bengal, India, Int. J. Epidemiol., 27 (5) (1998) 871–877.
  • [5] Abernathy C.O., Liu Y.P., Longfellow D., Aposhian H.V., Beck B., Fowler B., Goyer R., Menzer R., Rossman T., Thompson C., Arsenic: Health Effects, Mechanisms of Actions, and Research Issues, Environ. Health Perspect., 107 (7) (1999) 593–597.
  • [6] Santra A., Gupta J., Das De B.K., Roy B., Mazumder D.N.G. Hepatic Manifestations in Chronic Arsenic Toxicity, Indian J. Gastroenterol., 18 (1999) 152–155.
  • [7] Nevens F., Staessen D., Sciot R., Van Damme B., Desmet V., Fevery J., De Groote J., Van Steenbergen W. Clinical Aspects of Incomplete Septal Cirrhosis in Comparison with Macronodular Cirrhosis, Gastroenterology, 106 (2) (1994) 459–463.
  • [8] Rahman M., Tondel M., Ahmad S.A., Chowdhury I.A., Faruquee M.H., Axelson O. Hypertension and Arsenic Exposure in Bangladesh, Hypertension, 33 (1) (1999) 74–78.
  • [9] Benowitz N.L. Cardiotoxicity in the Workplace, Occup. Med., 7 (3) (1992) 465–478.
  • [10] Goldsmith S., Arthur H.L., Arsenic-Induced Atypical Ventricular Tachycardia, N. Engl. J. Med., 303 (19) (1980) 1096–1098.
  • [11] Schenk V.W., Stolk P.J., Psychosis Following Arsenic (Possibly Thallium) Poisoning, Psychiatr. Neurol. Nurochirurgia, 70 (1) (1967) 31–37.
  • [12] Guo H.R., Chiang H.S., Hu H., Lipsitz S.R., Monson R.R., Arsenic in Drinking Water and Incidence of Urinary Cancers, Epidemiology, 8 (5) (1997) 545–550.
  • [13] Rahman M., Tondel M., Ahmad S.A., Axelson O., Diabetes Mellitus Associated with Arsenic Exposure in Bangladesh, Am. J. Epidemiol., 148 (2) (1998) 198–203.
  • [14] Zhai Q., Narbad A., Chen W., Dietary Strategies for the Treatment of Cadmium and Lead Toxicity, Nutrients, 7 (1) (2015) 552–571.
  • [15] Gupta R., Flora S.J.S., Therapeutic Value of Hippophae Rhamnoides L. against Subchronic Arsenic Toxicity in Mice, J. Med. Food, 8 (3) (2005) 353–361.
  • [16] Nurchi V.M., Djordjevic A.B., Crisponi G., Alexander J., Bjørklund G., Aaseth J., Arsenic Toxicity: Molecular Targets and Therapeutic Agents, Biomolecules, 10 (2) (2020) 235.
  • [17] Jarjou’i A., Izbicki G., Medical Cannabis in Asthmatic Patients, Isr. Med. Assoc. J., 22 (4) (2020) 232–235.
  • [18] Booz G.W., Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress, Free Radic. Biol. Med., 51 (5) (2011) 1054–1061.
  • [19] Şahin S., Azarkan S.Y., Türksoy V.A., Evaluation of the Effect of Cannabidiol on the THLE-2 Liver Cell Line Exposed to Lead, Sci. Total Environ., 923 (2024) 170901.
  • [20] Styblo M., Razo L.M. Del Vega L., Germolec D.R., Lecluyse E.L., Hamilton G.A., Reed W., Wang C., Cullen W.R., Thomas D.J., Comparative Toxicity of Trivalent and Pentavalent Inorganic and Methylated Arsenicals in Rat and Human Cells, Arch Toxicol., 74 (2000) 289–299.
  • [21] Gęgotek A., Atalay S., Domingues P., Skrzydlewska E., The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts Following UVA or UVB Irradiation in 2D and 3D Cell Cultures, Cells, 8 (9) (2019) 995.
  • [22] Etienne de M., Fibre Hemp Cultivars: A Survey of Origin, Ancestry, Availabilityand Brief Agronomic Characteristics, J. Int. Hemp Assoc., 2 (1995) 67–73.
  • [23] Fitzcharles M., Clauw D.J., Hauser W.A., Cautious Hope for Cannabidiol (CBD) in Rheumatology Care, Arthritis Care Res. (Hoboken), 75 (6) (2023) 1371–1375.
  • [24] Niesink R.J.M., van Laar M.W., Does Cannabidiol Protect Against Adverse Psychological Effects of THC?, Front. psychiatry, 4 (2013) 130.
  • [25] Patel P.N., Pathak R., Rimonabant: A Novel Selective Cannabinoid-1 Receptor Antagonist for of Treatment Obesity, Am. J. Heal. Pharm., 64 (5) (2007) 481–489.
  • [26] Gelfand E.V., Cannon C.P., Rimonabant: A Selective Blocker of the Cannabinoid CB1 Receptors for the Management of Obesity, Smoking Cessation and Cardiometabolic Risk Factors, Expert Opin. Investig. Drugs, 15 (3) (2006) 307–315.
  • [27] Penner E.A., Buettner H., Mittleman M.A., The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults, Am. J. Med., 126 (7) (2013) 583–589.
  • [28] Weiss L., Zeira M., Reich S., Har-Noy M., Mechoulam R., Slavin S., Gallily R., Cannabidiol Lowers Incidence of Diabetes in Non-Obese Diabetic Mice, Autoimmunity, 39 (2) (2006) 143–151.
  • [29] Chen J., Hou C., Chen X., Wang D., Yang P., He X., Zhou J., Li H., Protective Effect of Cannabidiol on Hydrogen Peroxide‑induced Apoptosis, Inflammation and Oxidative Stress in Nucleus Pulposus Cells, Mol. Med. Rep., 14 (3) (2016) 2321–2327.
  • [30] Rajesh M., Mukhopadhyay P., Btkai S., Patel V., Saito K., Matsumoto S., Kashiwaya Y., Horvth B., Mukhopadhyay B.,
There are 30 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Toxicology, Basic Pharmacology
Journal Section Natural Sciences
Authors

Serkan Şahin 0000-0001-7000-6342

Vugar Ali Türksoy 0000-0002-3545-3945

Serap Yalcin 0000-0002-9584-266X

Project Number 6608-TF/21-475
Publication Date March 25, 2025
Submission Date January 9, 2025
Acceptance Date March 17, 2025
Published in Issue Year 2025Volume: 46 Issue: 1

Cite

APA Şahin, S., Türksoy, V. A., & Yalcin, S. (2025). Investigating the Efficacy of Cannabidiol Against Arsenic-Induced Liver Cell Damage. Cumhuriyet Science Journal, 46(1), 55-61. https://doi.org/10.17776/csj.1616411
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