In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA

<h3>Background</h3><p dir="ltr">The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the path...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Ayman Alzu’bi (13162392) (author)
مؤلفون آخرون: Ejlal Abu-El-Rub (5168183) (author), Bahaa Al-Trad (3574976) (author), Hiba Alzoubi (18001609) (author), Hadeel Abu-El-Rub (22052093) (author), Dima Albals (22052096) (author), Gamal T. Abdelhady (13162395) (author), Noor S. Bader (22052099) (author), Rawan Almazari (21842705) (author), Raed M. Al-Zoubi (2037490) (author)
منشور في: 2024
الموضوعات:
الوسوم: إضافة وسم
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author Ayman Alzu’bi (13162392)
author2 Ejlal Abu-El-Rub (5168183)
Bahaa Al-Trad (3574976)
Hiba Alzoubi (18001609)
Hadeel Abu-El-Rub (22052093)
Dima Albals (22052096)
Gamal T. Abdelhady (13162395)
Noor S. Bader (22052099)
Rawan Almazari (21842705)
Raed M. Al-Zoubi (2037490)
author2_role author
author
author
author
author
author
author
author
author
author_facet Ayman Alzu’bi (13162392)
Ejlal Abu-El-Rub (5168183)
Bahaa Al-Trad (3574976)
Hiba Alzoubi (18001609)
Hadeel Abu-El-Rub (22052093)
Dima Albals (22052096)
Gamal T. Abdelhady (13162395)
Noor S. Bader (22052099)
Rawan Almazari (21842705)
Raed M. Al-Zoubi (2037490)
author_role author
dc.creator.none.fl_str_mv Ayman Alzu’bi (13162392)
Ejlal Abu-El-Rub (5168183)
Bahaa Al-Trad (3574976)
Hiba Alzoubi (18001609)
Hadeel Abu-El-Rub (22052093)
Dima Albals (22052096)
Gamal T. Abdelhady (13162395)
Noor S. Bader (22052099)
Rawan Almazari (21842705)
Raed M. Al-Zoubi (2037490)
dc.date.none.fl_str_mv 2024-08-09T03:00:00Z
dc.identifier.none.fl_str_mv 10.1007/s11419-024-00699-9
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/In_vivo_assessment_of_the_nephrotoxic_effects_of_the_synthetic_cannabinoid_AB-FUBINACA/29907278
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Acute kidney injury
KIM-1
NGAL
dc.title.none.fl_str_mv In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood.</p><h3>Methods</h3><p dir="ltr">We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I–V) in renal tissues were also assessed.</p><h3>Results</h3><p dir="ltr">Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV.</p><h3>Conclusion</h3><p dir="ltr">These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.</p><h2>Other Information</h2><p dir="ltr">Published in: Forensic Toxicology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11419-024-00699-9" target="_blank">https://dx.doi.org/10.1007/s11419-024-00699-9</a></p>
eu_rights_str_mv openAccess
id Manara2_4febea1894cb872f44b5255f1082b794
identifier_str_mv 10.1007/s11419-024-00699-9
network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/29907278
publishDate 2024
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spelling In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACAAyman Alzu’bi (13162392)Ejlal Abu-El-Rub (5168183)Bahaa Al-Trad (3574976)Hiba Alzoubi (18001609)Hadeel Abu-El-Rub (22052093)Dima Albals (22052096)Gamal T. Abdelhady (13162395)Noor S. Bader (22052099)Rawan Almazari (21842705)Raed M. Al-Zoubi (2037490)Biomedical and clinical sciencesClinical sciencesPharmacology and pharmaceutical sciencesSynthetic cannabinoidsAB-FUBINACAAcute kidney injuryKIM-1NGAL<h3>Background</h3><p dir="ltr">The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood.</p><h3>Methods</h3><p dir="ltr">We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I–V) in renal tissues were also assessed.</p><h3>Results</h3><p dir="ltr">Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV.</p><h3>Conclusion</h3><p dir="ltr">These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.</p><h2>Other Information</h2><p dir="ltr">Published in: Forensic Toxicology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11419-024-00699-9" target="_blank">https://dx.doi.org/10.1007/s11419-024-00699-9</a></p>2024-08-09T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11419-024-00699-9https://figshare.com/articles/journal_contribution/In_vivo_assessment_of_the_nephrotoxic_effects_of_the_synthetic_cannabinoid_AB-FUBINACA/29907278CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/299072782024-08-09T03:00:00Z
spellingShingle In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
Ayman Alzu’bi (13162392)
Biomedical and clinical sciences
Clinical sciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Acute kidney injury
KIM-1
NGAL
status_str publishedVersion
title In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
title_full In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
title_fullStr In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
title_full_unstemmed In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
title_short In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
title_sort In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA
topic Biomedical and clinical sciences
Clinical sciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Acute kidney injury
KIM-1
NGAL