Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 6; p. 736
• Main Authors: Elgazzar, Dina, Aboubakr, Mohamed, Bayoumi, Heba, Ibrahim, Amany N., Sorour, Safwa M., El-Hewaity, Mohamed, Elsayed, Abulmaaty M., Shehata, Shaimaa A., Bayoumi, Khaled A., Alsieni, Mohammed, Behery, Maged, Abdelrahaman, Doaa, Ibrahim, Samah F., Abdeen, Ahmed
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 10.06.2022; MDPI
• Subjects: aminoglycosides; Animals; annexin-V; Antibiotics; Apoptosis; Cell cycle; Creatinine; Infections; inflammatory cytokines; kidney injury; Microorganisms; oxidative damage; Oxidative stress; Pathogens; Protein expression; tetracyclines
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15060736

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.