Bustos Pamela Soledad, Echeverría Javier, Páez Paulina Laura, Ortega María Gabriela
Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Córdoba, Argentina.
Front Pharmacol. 2025 Jul 31;16:1626058. doi: 10.3389/fphar.2025.1626058. eCollection 2025.
The induction of oxidative stress (OS) in host cells by antibiotics (ATBs) such as ciprofloxacin (CIP) and chloramphenicol (CMP) is associated with their side effects. Flavonoids such as quercetin (Q) and luteolin (LT) could counteract the harmful effects related to OS induced by ATBs.
The purpose of this research was to investigate the effect of CIP and CMP alone and plus Q and LT on ROS production, endogenous antioxidant defenses [superoxide dismutase (SOD) and catalase (CAT)], and protein oxidation (PO) on human leukocytes, evaluating the protective action of Q and LT on the toxicological effects of CIP and CMP.
Q and LT were isolated from leaves and fruits, respectively, and identified by spectroscopic and chromatographic techniques. Cell viability was assessed by the exclusion of the dye trypan blue, and intracellular reactive oxygen species (ROS) were detected by fluorescence using the H2-DCFDA assay. Riboflavin/methionine/NBT and H2O2/dichromate/acetic acid reagents, respectively determined SOD and CAT activities. The advanced oxidation protein products assay was used to assess PO. Q and LT interactions with CIP and CMP were evaluated by checkerboard assay in and .
Both ATBs were capable of increasing ROS production in polymorphonuclear cells, and Q and LT were more effective in inhibiting it than vitamin C. Regarding SOD and CAT activity, CIP and CMP altered their activity. Regardless of an increase in enzymatic activity, as in the case of CIP, or a decrease in antioxidant systems, as in the case of CMP, both flavonoids restore enzymatic activity to similar values as those of control cells. Concerning the PO increase observed by CIP and CMP, both Q and LT can prevent it. Finally, the association of flavonoids and ATBs on antimicrobial activity in and shows antibacterial synergism between LT and both ATBs in the ATCC strain, thereby enhancing antibacterial activity.
These findings stimulate in vivo research to assess if simultaneous administration of LT/Q with CIP/CMP could be a therapeutic option capable of protecting the host against antibiotic-induced OS in systemic circulation, enhancing antibacterial activity in case of LT. More studies are necessary in order to contribute to this hypothesis.
环丙沙星（CIP）和氯霉素（CMP）等抗生素在宿主细胞中诱导氧化应激（OS）与它们的副作用有关。槲皮素（Q）和木犀草素（LT）等黄酮类化合物可以抵消抗生素诱导的OS相关有害影响。
本研究旨在调查单独使用CIP和CMP以及添加Q和LT对人白细胞中活性氧（ROS）产生、内源性抗氧化防御[超氧化物歧化酶（SOD）和过氧化氢酶（CAT）]以及蛋白质氧化（PO）的影响，评估Q和LT对CIP和CMP毒理学效应的保护作用。
分别从叶子和果实中分离出Q和LT，并通过光谱和色谱技术进行鉴定。通过台盼蓝拒染法评估细胞活力，使用H2-DCFDA测定法通过荧光检测细胞内活性氧（ROS）。核黄素/蛋氨酸/NBT和过氧化氢/重铬酸盐/乙酸试剂分别测定SOD和CAT活性。采用高级氧化蛋白产物测定法评估PO。通过棋盘法在……中评估Q和LT与CIP和CMP的相互作用。
两种抗生素均能够增加多形核细胞中的ROS产生，并且Q和LT在抑制ROS产生方面比维生素C更有效。关于SOD和CAT活性，CIP和CMP改变了它们的活性。无论是像CIP那样酶活性增加，还是像CMP那样抗氧化系统减少，两种黄酮类化合物都能将酶活性恢复到与对照细胞相似的值。关于CIP和CMP观察到的PO增加，Q和LT都可以预防。最后，黄酮类化合物与抗生素在……中的抗菌活性关联显示，在ATCC菌株中LT与两种抗生素之间存在抗菌协同作用，从而增强抗菌活性。
这些发现促使开展体内研究，以评估LT/Q与CIP/CMP同时给药是否可能是一种能够保护宿主免受全身循环中抗生素诱导的OS影响、在LT存在时增强抗菌活性的治疗选择。为了支持这一假设，还需要更多研究。
