Solomon Owumi , Joseph Chimezie , Idris O. Bello , Moses T. Otunla , Uche Arunsi , Ayomide P. Akomolafe , Jesutosin O. Babalola , Chioma E. Irozuru , Olatunde O. Owoeye
{"title":"Azithromycin and Gallic acid alleviate neurobehavioral deficits in rats resulting from chronic Aflatoxin B1 exposure","authors":"Solomon Owumi , Joseph Chimezie , Idris O. Bello , Moses T. Otunla , Uche Arunsi , Ayomide P. Akomolafe , Jesutosin O. Babalola , Chioma E. Irozuru , Olatunde O. Owoeye","doi":"10.1016/j.toxicon.2025.108552","DOIUrl":null,"url":null,"abstract":"<div><div>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) is a mycotoxin known for its liver toxicity and cancer risk, as well as neurotoxic effects causing motor and cognitive issues in humans and animals. Ongoing research into protecting against AFB<sub>1</sub> damage has recently focused on antioxidant and anti-inflammatory agents. Gallic acid (GA), a low molecular weight triphenolic acid, demonstrates notable anti-oxidative and anti-inflammatory activities. Furthermore, Azithromycin (AZT), an antibiotic, has shown promise in mitigating inflammatory stress in experimental models. GA and AZT may help protect against AFB<sub>1</sub>-induced neurobehavioral deficits in rats. This experiment involved thirty-five rats randomly assigned to seven cohorts (n = 5), over a 28-day treatment period. The study consisted of a control group given corn oil, a group exposed only to AFB<sub>1</sub>, and groups that received GA, AZT, or combinations of these substances with AFB<sub>1</sub>. The neurobehavioral status of the experimental rats was assessed using the Open Field Test (OFT) and Novel Object Recognition Test (NORT) on days 26 and 27, respectively. On day 28 following treatment, the Elevated Plus Maze (EPM), Y-maze, and Forced Swim Test (FST) were conducted. After behavioural evaluation, the rats were euthanised. The hippocampus and prefrontal cortex were dissected for biochemical analysis. Antioxidant enzyme activities (SOD, CAT, GPx, GST), GSH and TSH levels, acetylcholinesterase, and markers of oxidative stress (RONS, LPO) and inflammation (NO, MPO) were measured. AFB<sub>1</sub> exposure raised oxidative stress markers, MPO, and AChE activity, while lowering antioxidant enzymes in the hippocampus and prefrontal cortex, indicating notable neurotoxicity and signalling disruptions. Combined GA and AZT treatment improved antioxidant defence, reduced inflammation, and restored AChE activity. Neurobehavioral tests indicated better motor and cognitive function after AFB<sub>1</sub> exposure. These results suggest that GA and AZT together offer strong protection against AFB1-induced neurotoxicity via their antioxidant and anti-inflammatory effects.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108552"},"PeriodicalIF":2.4000,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041010125003277","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Aflatoxin B1 (AFB1) is a mycotoxin known for its liver toxicity and cancer risk, as well as neurotoxic effects causing motor and cognitive issues in humans and animals. Ongoing research into protecting against AFB1 damage has recently focused on antioxidant and anti-inflammatory agents. Gallic acid (GA), a low molecular weight triphenolic acid, demonstrates notable anti-oxidative and anti-inflammatory activities. Furthermore, Azithromycin (AZT), an antibiotic, has shown promise in mitigating inflammatory stress in experimental models. GA and AZT may help protect against AFB1-induced neurobehavioral deficits in rats. This experiment involved thirty-five rats randomly assigned to seven cohorts (n = 5), over a 28-day treatment period. The study consisted of a control group given corn oil, a group exposed only to AFB1, and groups that received GA, AZT, or combinations of these substances with AFB1. The neurobehavioral status of the experimental rats was assessed using the Open Field Test (OFT) and Novel Object Recognition Test (NORT) on days 26 and 27, respectively. On day 28 following treatment, the Elevated Plus Maze (EPM), Y-maze, and Forced Swim Test (FST) were conducted. After behavioural evaluation, the rats were euthanised. The hippocampus and prefrontal cortex were dissected for biochemical analysis. Antioxidant enzyme activities (SOD, CAT, GPx, GST), GSH and TSH levels, acetylcholinesterase, and markers of oxidative stress (RONS, LPO) and inflammation (NO, MPO) were measured. AFB1 exposure raised oxidative stress markers, MPO, and AChE activity, while lowering antioxidant enzymes in the hippocampus and prefrontal cortex, indicating notable neurotoxicity and signalling disruptions. Combined GA and AZT treatment improved antioxidant defence, reduced inflammation, and restored AChE activity. Neurobehavioral tests indicated better motor and cognitive function after AFB1 exposure. These results suggest that GA and AZT together offer strong protection against AFB1-induced neurotoxicity via their antioxidant and anti-inflammatory effects.
期刊介绍:
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.