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

替加环素和庆大霉素联合治疗增强肾脏损伤:氧化应激、炎症反应和细胞凋亡的相互作用

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作者:Dina Elgazzar, Mohamed Aboubakr, Heba Bayoumi, Amany N Ibrahim, Safwa M Sorour, Mohamed El-Hewaity, Abulmaaty M Elsayed, Shaimaa A Shehata, Khaled A Bayoumi, Mohammed Alsieni, Maged Behery, Doaa Abdelrahaman, Samah F Ibrahim, Ahmed Abdeen

Abstract

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.

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