Abstract
Objectives
Khat (Catha edulis) is a stimulant plant, and it is abusive to induce euphoria, alertness and activity. Concomitant use of medications and khat chewing predisposes to the appearance of drug interactions result in treatment failure or toxicity. This study determined the changes in the urinary inorganic profile in adult healthy males who are chewing khat compared with non-khat chewer males.
Methods
A total of 40 adult non-smoker healthy males (20 khat chewer and 20 non-khat chewer) aged 24–30 years were selected. Khat chewer samples were positive for cathinone and cathine and negative for other drug of abuse, while non-khat chewer samples were negative for drug of abuse include cathinone and cathine. Samples were selected according to their results in immunoassay and gas chromatography mass spectrometry (GCMS) analysis. Cathine and cathinone were confirmed using liquid chromatography mass spectrometry (LC-MSMS) analysis. Inorganic profile includes titanium (Ti), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) were determined by using inductively coupled plasma-mass spectrometry (ICP-MS).
Results
The levels of Ti, Co, Zn, Cd, and Pb in urine were significantly higher among the khat chewer group compared with non-khat chewer. Ti, Cd, Co, Pb and Zn urine levels were 0.5-, 1.5-, 1.15-, 5-, and 8.2-fold higher in the khat chewer group compared to non-khat chewer, respectively.
Conclusions
We suggested that continuous khat chewing has a long term effect on metabolic pathway of therapeutic drugs that result in toxicity or failure of therapy.
Acknowledgments
The authors thank Jazan poison control center staff whose support this work.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Ibraheem M. Attafi contributed significantly in designed and conducted the experiments and analysis of data. Ahmed M Hakami and Mohammed A Attafi contributed in sample preparation, analysis and acquisition of data. Ibraheem M. Attafi and Mohammed Y Albeishy contributed in designed the experiments and analysis and interpretation of data. Ibraheem M. Attafi, Mohammed Y Albeishy, and Ibrahim A Khardali discussed the results and wrote the manuscript.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: Not applicable.
References
1. Drug Enforcement Administration. Drugs of abuse: a dea resource guide. Available from: https://www.dea.gov/sites/default/files/2020-04/Drugs%20of%20Abuse%202020-Web%20Version-508%20compliant-4-24-20_0.pdf [Accessed 14 Apr 2020].Search in Google Scholar
2. Al-Habori, M. The potential adverse effects of habitual use of Catha edulis (khat). Expet Opin Drug Saf 2005;4:1145–54.10.1517/14740338.4.6.1145Search in Google Scholar PubMed
3. Cox, G, Rampes, H. Adverse effects of khat: a review. Adv Psychiatr Treat 2003;9:456–63.10.1192/apt.9.6.456Search in Google Scholar
4. Raja’a, YA, Noman, TA, Al-Warafi, AK, Al Mashraki, NA, Al Yosofi, AM. Khat chewing is a risk factor of duodenal ulcer. Saudi Med J 2000;21:887–8.Search in Google Scholar
5. Al-Hadrani, AM. Khat induced hemorrhoidal disease in Yemen. Saudi Med J 2000;21:475–7.Search in Google Scholar
6. Kariri, AM, Darraj, MA, Wassly, A, Arishi, HA, Lughbi, M, Kariri, A, et al.. Prevalence and risk factors of gastroesophageal reflux disease in Southwestern Saudi Arabia. Cureus 2020;12:e6626.10.7759/cureus.6626Search in Google Scholar PubMed PubMed Central
7. Abebe, W. Khat: a substance of growing abuse with adverse drug interaction risks. J Natl Med Assoc 2018;110:624–34.10.1016/j.jnma.2018.04.001Search in Google Scholar PubMed
8. Al-Motarreb, AL, Broadley, KJ. Coronary and aortic vasoconstriction by cathinone, the active constituent of khat. Auton Autacoid Pharmacol 2003;23:319–26.10.1111/j.1474-8673.2004.00303.xSearch in Google Scholar PubMed
9. Alkadi, H, Al-Kamarany, M, Al-Kadi, H, Lyoussi, B, Khalil, K. Khat-aspirin interaction. Yemen J Pharm Biol Sci 2008;2:e39.Search in Google Scholar
10. Kalix, P. Khat, an amphetamine-like stimulant. J Psychoact Drugs 1994;26:69–74.10.1080/02791072.1994.10472604Search in Google Scholar PubMed
11. Patel, NB. Mechanism of action of cathinone: the active ingredient of khat (Catha edulis). East Afr Med J 2000;77:329–32.10.4314/eamj.v77i6.46651Search in Google Scholar PubMed
12. Bedada, W, de Andres, F, Engidawork, E, Pohanka, A, Beck, O, Bertilsson, L, et al.. The psychostimulant khat (Catha edulis) inhibits CYP2D6 enzyme activity in humans. J Clin Psychopharmacol 2015;35:694–9.10.1097/JCP.0000000000000413Search in Google Scholar PubMed
13. Bedada, W, de Andres, F, Engidawork, E, Hussein, J, A, LL, Aklillu, E. Effects of khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations. Sci Rep 2018;8:12726.10.1038/s41598-018-31191-1Search in Google Scholar PubMed PubMed Central
14. Hakami, M, Jammaly, A, Attafi, I, Oraiby, M, Jeraiby, M. Acute myocardial infarction associated with ingestion of herbal mixtures containing acetylcholinesterase inhibitors: a case study. Int J Med Health Biomed Bioeng Pharm Eng 2017;11:37–42.Search in Google Scholar
15. Attafi, IM, Albeishy, MY, Oraiby, ME, Khardali, IA, Shaikhain, GA, Fageeh, MM. Postmortem distribution of cathinone and cathine in human biological specimens in a case of death associated with khat chewing. Arab J Forensic Sci Forensic Med 2018;1:922–30.10.26735/16586794.2018.013Search in Google Scholar
16. Albeishy, MY, Oraiby, ME, Khawaji, MM, Arishy, MA, Attafi, IM. Postmortem tissue distribution of citalopram in a case of carbon monoxide poisoning. Arab J Forensic Sci Forensic Med 2020;2:75–9.10.26735/UCDT2862Search in Google Scholar
17. Al Bakheet, SA, Attafi, IM, Maayah, ZH, Abd-Allah, AR, Asiri, YA, Korashy, HM. Effect of long-term human exposure to environmental heavy metals on the expression of detoxification and DNA repair genes. Environ Pollut 2013;181:226–32.10.1016/j.envpol.2013.06.014Search in Google Scholar
18. Menke, A, Muntner, P, Silbergeld, EK, Platz, EA, Guallar, E. Cadmium levels in urine and mortality among US adults. Environ Health Perspect 2009;117:190–6.10.1289/ehp.11236Search in Google Scholar
19. Matloob, MH. Determination of cadmium, lead, copper and zinc in Yemeni khat by anodic stripping voltammetry. East Mediterr Health J 2003;9:28–36.10.26719/2003.9.1-2.28Search in Google Scholar
20. Nakasuji, K, Usuda, K, Kawasaki, T, Dote, E, Hayashi, S, Mitsui, G, et al.. Urinary and serum titanium: assessment as an indicator of exposure to ammonium citratoperoxotitanate (IV) and its influence on renal function. Biol Trace Elem Res 2006;110:119–32.10.1385/BTER:110:2:119Search in Google Scholar
21. Järup, L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167–82.10.1093/bmb/ldg032Search in Google Scholar PubMed
22. Alsalahi, A, Alshawsh, MA, Chik, Z, Mohamed, Z. Effect of Catha edulis (khat) on pancreatic functions in streptozotocin-induced diabetes in male Sprague-Dawley rats. Exp Anim 2018;67:517–26.10.1538/expanim.18-0057Search in Google Scholar PubMed PubMed Central
23. Bahijri, SM, Alissa, EM. Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults. J Clin Biochem Nutr 2011;49:164–8.10.3164/jcbn.10-148Search in Google Scholar PubMed PubMed Central
24. Baselt, RC. Disposition of toxic drugs and chemicals in man. Seal Beach, California: Biomedical Publications; 2002.Search in Google Scholar
25. Leyssens, L, Vinck, B, Van Der Straeten, C, Wuyts, F, Maes, L. Cobalt toxicity in humans-a review of the potential sources and systemic health effects. Toxicology 2017;387:43–56.10.1016/j.tox.2017.05.015Search in Google Scholar PubMed
26. Ismail, AA, Almalki, M, Agag, A, Solan, YM, Bani, IA. Pesticide application and khat chewing as predictors of the neurological health outcomes among pesticide applicators in a vector control unit, Saudi Arabia. Int J Occup Environ Med 2018;9:32–44.10.15171/ijoem.2018.1160Search in Google Scholar PubMed PubMed Central
27. Bora, BK, Ramos-Crawford, AL, Sikorskii, A, Boivin, MJ, Lez, DM, Mumba-Ngoyi, D, et al.. Concurrent exposure to heavy metals and cognition in school-age children in Congo-Kinshasa: a complex overdue research agenda. Brain Res Bull 2019;145:81–6.10.1016/j.brainresbull.2018.06.013Search in Google Scholar PubMed PubMed Central
28. Fraker, PJ, Jardieu, P, Cook, J. Zinc deficiency and immune function. Arch Dermatol 1987;123:1699–701.10.1001/archderm.1987.01660360152028Search in Google Scholar
29. Yimer, A, Khan, M. Determination of iron, cobalt, chromium and copper metals in commercially available khat (Catha Edulis Forsk) in Arba Minch, Ethiopia, Int J Engin Res Appl 2015;5:66–74.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Oxy+ (arthrospira) and its medicinal importance: an appraisal
- Original Articles
- In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6
- Efficacy of Majoon-e-Seer Alvi Khan in dyslipidemia: a single blind randomized standard controlled clinical trial
- Prevalence of alcohol-drug interactions in community-dwelling older patients with polypharmacy
- Evaluation of the need for pharmacogenomics testing among physicians in the West Bank of Palestine
- Habitual khat chewing alters urinary inorganic profile in adult healthy males
- Trichostatin A sensitizes hepatoma cells to Taxol more than 5-Aza-dC and dexamethasone
- Ocimum gratissimum leaf extract ameliorates phenylhydrazine-induced anaemia and toxicity in Wistar rats
- Lactobacillus plantarum mitigates sexual-reproductive deficits by modulating insulin receptor expression in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice
- Consumption of Ashtanga Ghrita (clarified cow butter added with herb extracts) improves cognitive dysfunction induced by scopolamine in rats via regulation of acetylcholinesterase activity and oxidative stress
- Letter to the Editor
- Fatal thiopurine toxicity: pre-emptive testing of NUDT15 415C>T polymorphism may be life saving in South Asian population
Articles in the same Issue
- Frontmatter
- Review
- Oxy+ (arthrospira) and its medicinal importance: an appraisal
- Original Articles
- In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6
- Efficacy of Majoon-e-Seer Alvi Khan in dyslipidemia: a single blind randomized standard controlled clinical trial
- Prevalence of alcohol-drug interactions in community-dwelling older patients with polypharmacy
- Evaluation of the need for pharmacogenomics testing among physicians in the West Bank of Palestine
- Habitual khat chewing alters urinary inorganic profile in adult healthy males
- Trichostatin A sensitizes hepatoma cells to Taxol more than 5-Aza-dC and dexamethasone
- Ocimum gratissimum leaf extract ameliorates phenylhydrazine-induced anaemia and toxicity in Wistar rats
- Lactobacillus plantarum mitigates sexual-reproductive deficits by modulating insulin receptor expression in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice
- Consumption of Ashtanga Ghrita (clarified cow butter added with herb extracts) improves cognitive dysfunction induced by scopolamine in rats via regulation of acetylcholinesterase activity and oxidative stress
- Letter to the Editor
- Fatal thiopurine toxicity: pre-emptive testing of NUDT15 415C>T polymorphism may be life saving in South Asian population