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...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513541065670656 |
|---|---|
| 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 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29907278 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| 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 |