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This research was supported by MCIN/AEI/10.13039/501100011033 (PID2019-111510RB-I00), Asociacion Espanola de Gastroenterologia-Asociacion Espanola de Neurogastroenterologia y Motilidad (Beca AEG-ASENEM, 2021), and the Irish Research Council (IRCL/2017/78). MAH was supported by a grant to ALB from Enterprise Ireland (Programme H2020 Proposal Preparation Support, CS20192034).

Analysis of institutional authors

Llorente-Berzal, AlvaroCorresponding Author
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Article

The Endocannabinoid System of the Nervous and Gastrointestinal Systems Changes after a Subnoxious Cisplatin Dose in Male Rats

Publicated to:Pharmaceuticals. 17 (10): 1256- - 2024-10-01 17(10), DOI: 10.3390/ph17101256

Authors: Lopez-Tofino, Yolanda; Hopkins, Mary A; Bagues, Ana; Boullon, Laura; Abalo, Raquel; Llorente-Berzal, Alvaro

Affiliations

Autonomous Univ Madrid UAM, Sch Med, Dept Physiol, Madrid 28049, Spain - Author
CSIC, Inst Med Chem IQM, Associated RDi Unit, Madrid 28006, Spain - Author
Spanish Pain Soc, Working Grp Basic Sci Cannabinoids, Madrid 28046, Spain - Author
Spanish Pain Soc, Working Grp Basic Sci Pain & Analgesia, Madrid 28046, Spain - Author
Univ Galway, Ctr Pain Res, Galway H91 W5P7, Ireland - Author
Univ Galway, Galway Neurosci Ctr, Galway H91 W5P7, Ireland - Author
Univ Galway, Sch Med, Dept Pharmacol & Therapeut, Galway H91 W5P7, Ireland - Author
Univ Rey Juan Carlos URJC, Dept Basic Hlth Sci, Alcorcon 28922, Spain - Author
Univ Rey Juan Carlos URJC, High Performance Res Grp Expt Pharmacol PHARMAKOM, Alcorcon 28922, Spain - Author
Univ Rey Juan Carlos URJC, High Performance Res Grp Physiopathol & Pharmacol, Alcorcon 28922, Spain - Author
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Abstract

Background/Objectives: Cisplatin, a common chemotherapy agent, is well known to cause severe side effects in the gastrointestinal and nervous systems due to its toxic and pro-inflammatory effects. Although pharmacological manipulation of the endocannabinoid system (ECS) can alleviate these side effects, how chemotherapy affects the ECS components in these systems remains poorly understood. Our aim was to evaluate these changes. Methods: Male Wistar rats received cisplatin (5 mg/kg, i.p.) or saline on day 0 (D0). Immediately after, serial X-rays were taken for 24 h (D0). Body weight was recorded (D0, D1, D2 and D7) and behavioural tests were performed on D4. On D7, animals were euthanized, and gastrointestinal tissue, dorsal root ganglia (DRGs) and brain areas were collected. Expression of genes related to the ECS was assessed via Rt-PCR, while LC-MS/MS was used to analyse endocannabinoid and related N-acylethanolamine levels in tissue and plasma. Results: Animals treated with cisplatin showed a reduction in body weight. Cisplatin reduced gastric emptying during D0 and decreased MAGL gene expression in the antrum at D7. Despite cisplatin not causing mechanical or heat sensitivity, we observed ECS alterations in the prefrontal cortex (PFC) and DRGs similar to those seen in other chronic pain conditions, including an increased CB1 gene expression in L4/L5 DRGs and a decreased MAGL expression in PFC. Conclusions: A single dose of cisplatin (5 mg/kg, i.p.), subnoxious, but capable of inducing acute gastrointestinal effects, caused ECS changes in both gastrointestinal and nervous systems. Modulating the ECS could alleviate or potentially prevent chemotherapy-induced toxicity.

Keywords
2-arachidonoylglycerolAcid amide hydrolaseAnandamideBrainCentral nervous systemChemotherapyCisplatiCisplatinDorsal root gangliaEndocannabinoid systemGastrointestinalModelMolecular-mechanismsMotilitPainPeripheral neuropathyReceptor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Pharmaceuticals due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 20/72, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Medicinal.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-09:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 5 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.

    There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (LLORENTE BERZAL, ALVARO).

    the author responsible for correspondence tasks has been LLORENTE BERZAL, ALVARO.