{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:13:25Z","timestamp":1770747205771,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2022R127"],"award-info":[{"award-number":["PNURSP2022R127"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg\/kg), TG14 (tigecycline, 14 mg\/kg), GM (gentamicin, 80 mg\/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.<\/jats:p>","DOI":"10.3390\/ph15060736","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7769-4125","authenticated-orcid":false,"given":"Dina","family":"Elgazzar","sequence":"first","affiliation":[{"name":"Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1719-4844","authenticated-orcid":false,"given":"Mohamed","family":"Aboubakr","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba","family":"Bayoumi","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amany N.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safwa M.","family":"Sorour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"El-Hewaity","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Menoufia University, Shebin Elkoum 32514, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abulmaaty M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Anatomy and Histology Department, Faculty of Medicine, Mutah University, Mutah 61710, Jordan"},{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaimaa A.","family":"Shehata","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-4044","authenticated-orcid":false,"given":"Khaled A.","family":"Bayoumi","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo 11956, Egypt"},{"name":"Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah 21442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-6041","authenticated-orcid":false,"given":"Mohammed","family":"Alsieni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maged","family":"Behery","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa","family":"Abdelrahaman","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-3296","authenticated-orcid":false,"given":"Samah F.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4907-955X","authenticated-orcid":false,"given":"Ahmed","family":"Abdeen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt"},{"name":"Center of Excellence for Screening of Environmental Contaminants (CESEC), Benha University, Toukh 13736, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.18632\/oncotarget.6419","article-title":"Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1\/Waf1-dependent manner","volume":"7","author":"Hu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dong, Z., Abbas, M.N., Kausar, S., Yang, J., Li, L., Tan, L., and Cui, H. 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