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Chronic Cd exposure promotes the excessive production of reactive oxygen species (ROS), which ultimately leads to oxidative stress, inflammatory responses, organ dysfunction, and neurobehavioral alterations.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Apis mellifera<\/jats:italic>\n                    <\/jats:styled-content>\n                    bee venom (BV) consists of a diverse mixture of biologically active peptides, including key components such as melittin and apamin with documented antioxidant, anti\u2010inflammatory, and neuroprotective properties. However, to date, no studies have directly investigated its potential to mitigate Cd\u2010induced multi\u2010organ toxicity. Therefore, the present study aimed to evaluate the protective effects of BV against Cd\u2010induced hepatorenal injury, oxidative imbalance, and anxiety\u2010like behavior in a rat model, and to investigate its potential as a natural therapeutic strategy against heavy metal\u2010induced systemic toxicity. Male Wistar rats were assigned to control, BV (1\u2009mg\/kg\/day, subcutaneous route), Cd (40\u2009mg\/L in drinking water), and Cd\u2009+\u2009BV for 14\u2009days. Anxiety\u2010like behavior was investigated using two behavioral tests, namely the elevated plus maze (EPM) and the open field test (OFT), while hepatic and renal function markers and oxidative stress parameters were quantified in plasma and tissue samples. BV composition was verified by RP\u2010HPLC ESI\u2010MS analysis, confirming melittin as the predominant peptide component. Cd exposure induced anxiety\u2010like behavior, elevated plasma ALT, AST, and urea levels, increased lipid peroxidation, and reduced antioxidant enzyme activities in brain, liver, and kidney. Co\u2010administration of BV markedly attenuated these behavioral and biochemical alterations, reducing MDA levels and restoring SOD and CAT activities. Collectively, these findings highlight the potential of BV to protect against Cd\u2010induced hepatorenal and neurobehavioral toxicity, likely through modulation of oxidative stress pathways, thereby underscoring its promise as a natural therapeutic candidate for mitigating oxidative damage induced by heavy metals.\n                  <\/jats:p>","DOI":"10.1002\/tox.70153","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:48:57Z","timestamp":1785584937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of Bee Venom (\n                    <scp>\n                      <i>Apis mellifera<\/i>\n                    <\/scp>\n                    ) Against Cadmium\u2010Induced Hepatorenal Toxicity, Oxidative Stress, and Anxiety\u2010Like Behavior in Rats"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3152-9666","authenticated-orcid":false,"given":"Soumaya","family":"Ghodbane","sequence":"first","affiliation":[{"name":"Faculty of Sciences of Bizerte, Laboratory of Integrative Physiology University of Carthage  Jarzouna Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chedli","family":"Ellijimi","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Tunis, LR20IPT01, Laboratoire Des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques, Universit\u00e9 Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rym","family":"Elfessi","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Tunis, Laboratoire Des Venins et Biomol\u00e9cules Th\u00e9rapeutiques, Universit\u00e9 Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranya","family":"Hezzi","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, Laboratory of Integrative Physiology University of Carthage  Jarzouna Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khemaies Ben","family":"Rhouma","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, Laboratory of Integrative Physiology University of Carthage  Jarzouna Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafedh","family":"Abdelmelek","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, Laboratory of Integrative Physiology University of Carthage  Jarzouna Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najet","family":"Srairi\u2010Abid","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Tunis, LR20IPT01, Laboratoire Des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques, Universit\u00e9 Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-3712","authenticated-orcid":false,"given":"Mohsen","family":"Sakly","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Bizerte, Laboratory of Integrative Physiology University of Carthage  Jarzouna Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4901-3100","authenticated-orcid":false,"given":"Riadh","family":"Marrouchi","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Tunis, Laboratoire Des Venins et Biomol\u00e9cules Th\u00e9rapeutiques, Universit\u00e9 Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"623","volume-title":"Casarett and Doull's Toxicology: The Basic Science of Poisons","author":"Goyer R. 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