Quercetin and Ciprofloxacin: Rat Study on Kidney Oxidative Stress

The study “Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats: A histological and biochemical study” by Elbe et al. (2016) looked at how quercetin, a plant flavonoid with antioxidant activity, might change kidney injury linked to ciprofloxacin use in rats. (PubMed) Ciprofloxacin is a widely used fluoroquinolone antibiotic, and although it is usually well tolerated, case reports and experimental work suggest that kidney toxicity can occur in some settings. The authors set up a controlled rat experiment to compare four groups: control, quercetin alone, ciprofloxacin alone, and ciprofloxacin plus quercetin. The goal was to see whether quercetin could change both the microscopic kidney damage and the biochemical signs of oxidative stress caused by ciprofloxacin. This blog summarizes and quotes that scientific paper and does not add new scientific claims beyond what the authors reported.

Ciprofloxacin belongs to the fluoroquinolone class and is used for infections in the respiratory tract, urinary tract, skin, bone, joints, and gut. The authors note that “rising cases of ciprofloxacin-associated organ toxicities have been reported,” including kidney problems such as acute kidney injury. Ciprofloxacin is mainly excreted through the kidneys, so these organs are exposed to the drug and any reactive byproducts for long periods.

Flavonoids are plant compounds with many reported biological activities, including anti-inflammatory, antiviral, antibacterial, and antitumor effects. Quercetin is one of the most common flavonoids and has been reported to “scavenge free radicals, directly inhibit biomolecule oxidation, prevent lipid damage, and alter antioxidant defense pathways in vivo and in vitro,” based on earlier experimental work. In this scientific paper, the authors wanted to know if quercetin could counter some of the oxidative stress and tissue damage caused by ciprofloxacin in the kidney. They specifically mention that, to their knowledge, “a histological study about beneficial effects of quercetin on ciprofloxacin-induced nephrotoxicity” had not been published before this work.

This scientific paper used an in vivo (animal) experimental design with twenty-eight female Wistar albino rats. The rats were housed under standard conditions and randomly divided into four groups of seven:

1. control (corn oil by gavage for 21 days),
2. quercetin alone (20 mg/kg/day by gavage for 21 days),
3. ciprofloxacin alone (20 mg/kg twice a day intraperitoneally for 10 days), and
4. ciprofloxacin + quercetin (same dosing as groups 2 and 3 combined).

At the end of the experiment, the rats were sacrificed under ketamine anesthesia and both kidneys were collected. For histology, kidney tissue was fixed in formalin, embedded in paraffin, cut at 5 μm, and stained with hematoxylin–eosin. The sections were scored semiquantitatively for several features of kidney injury, including inflammatory cell infiltration, dilatation of tubules, tubular atrophy, reduction of Bowman’s space, congestion, hemorrhage, and tubular necrosis. Each feature was graded from 0 (normal) to 3 (severe), and a mean histopathological damage score (MHDS) was calculated.

For biochemistry, the remaining kidney tissue was homogenized, and several oxidative stress markers were measured. Malondialdehyde (MDA), an end product of lipid peroxidation, was quantified as thiobarbituric acid reactive substances. Glutathione (GSH) levels were measured using Ellman’s method. Superoxide dismutase (SOD) activity was measured by its ability to inhibit nitroblue tetrazolium reduction, and catalase (CAT) activity was measured by the rate of hydrogen peroxide breakdown. Protein concentrations were used to express specific enzyme activities. Non-normal data distributions were analyzed with non-parametric tests (Kruskal–Wallis and Mann–Whitney U), and p < 0.05 was considered statistically significant.

In the control and quercetin-only groups, kidney histology looked normal, and there was no significant difference between these groups in the mean histopathological damage score (MHDS). In contrast, the ciprofloxacin group showed clear kidney injury. The authors report “peritubular infiltration, tubular dilatation, tubular atrophy, hemorrhage, and tubular necrosis,” along with congestion and a reduction of Bowman’s space in affected glomeruli.

The MHDS in the ciprofloxacin group was 11.42 ± 0.42, which was significantly higher than scores in the control and quercetin groups (p < 0.001). In the ciprofloxacin + quercetin group, these histopathological changes were “markedly reduced,” and the MHDS fell to 6.42 ± 0.97. When the ciprofloxacin group was compared with the ciprofloxacin + quercetin group, the MHDS decrease was statistically significant (p < 0.005). These findings suggest that, in this rat model, quercetin co-treatment was associated with a lower severity of structural kidney damage linked to ciprofloxaci

The biochemical data were consistent with the histology findings. In the ciprofloxacin group, mean kidney tissue levels of malondialdehyde (MDA) were significantly higher than in the control and quercetin groups, indicating more lipid peroxidation and oxidative damage. In the ciprofloxacin + quercetin group, MDA levels were significantly lower than in the ciprofloxacin-only group, showing a shift toward less oxidative stress.

Antioxidant defenses were also affected. In the ciprofloxacin group, GSH levels and the activities of SOD and CAT were all significantly decreased compared with the control group. In the ciprofloxacin + quercetin group, GSH levels and SOD and CAT activities were significantly higher than in the ciprofloxacin-only group. The authors state that “quercetin treatment elevated antioxidant parameters, including activities of SOD and CAT and levels of GSH,” and note that these biochemical findings were consistent with the histopathological results.

In the discussion, the authors connect these results to what is already known about ciprofloxacin and oxidative stress. Previous studies have shown that ciprofloxacin can stimulate the production of reactive oxygen species (ROS) in different cell types. The formation of free radicals and oxidative metabolites is thought to be an important mechanism behind tissue damage, including nephrotoxicity. In this scientific paper, the pattern of increased MDA and decreased GSH, SOD, and CAT in the ciprofloxacin group matches this oxidative stress model.

Quercetin, on the other hand, is described as a compound that “scavenges free radicals directly, inhibits biomolecule oxidation, prevents lipid damage and alters antioxidant defense pathways in vivo and in vitro.” In this rat kidney model, quercetin administration in the ciprofloxacin + quercetin group increased antioxidant enzyme activities and reduced MDA levels, which fits the idea that quercetin can support endogenous antioxidant defenses. The authors conclude that, in this rat model, “administration of quercetin maintains antioxidant defenses and reduces renal oxidative damage” in the setting of ciprofloxacin toxicity. (PubMed)

The authors interpret their data as evidence that quercetin has “antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.” They note that this is, to their knowledge, the first histological and biochemical study to test quercetin in ciprofloxacin-induced nephrotoxicity in this way. The findings suggest that oxidative stress plays a key role in the kidney damage seen with ciprofloxacin in this model, and that quercetin co-treatment can shift both tissue structure and antioxidant markers in a favorable direction.

At the same time, the study is limited to a small animal model, with only twenty-eight female rats and a specific dosing schedule and duration. The authors emphasize that ciprofloxacin is still considered a “safe and useful antibacterial agent” but suggest that clinicians should remain careful about possible kidney effects and check kidney function before use. The scientific paper does not test quercetin in humans and does not provide dosing advice for people; the conclusions apply only to this rat model. This blog stays within those reported findings and does not turn them into clinical recommendations.

In summary, this 2016 scientific paper reports that ciprofloxacin led to kidney injury and oxidative stress in Wistar rats, and that co-treatment with quercetin was linked to less histological damage and different oxidative stress markers in this specific model.

In ciprofloxacin-treated kidneys, quercetin was associated with a lower mean histopathological damage score, lower MDA, and higher GSH, SOD, and CAT activities. The authors conclude that quercetin “has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats,” while also noting that ciprofloxacin remains an important antibacterial drug. This blog summarizes and paraphrases those findings in more accessible language, without adding claims beyond what the scientific paper reported.