Investigation of the Effects of Rutin on Sciatic Nerve Damage Induced by Colistin in Rats

Year 2025, Volume: 1 Issue: 1, 29 - 35, 30.09.2025

Fatih Mehmet Kandemir , Hasan Şimşek

Abstract

Introduction: This study aimed to determine the protective effect of Rutin on Colistin-induced sciatic nerve injury.
Methods: Thirty-five rats were divided into five groups: control, Rutin, Colistin, Colistin+Rutin50, and Colistin+Rutin100. Biochemically, malondialdehyde (MDA), glial fibrillary acidic protein (GFAP), nerve cell adhesion molecule (NCAM), nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), and neuronal nitric oxide synthase (nNOS), and parameters were analyzed.
Results: Colistin treatment caused sciatic nerve injury by increasing MDA levels (p < 0.05) leading to lipid peroxidation; by increasing COX-2, NF-κB, and nNOS levels (p < 0.05) leading to inflammation; and by increasing GFAP levels and decreasing NCAM levels (p < 0.05). Colistin+Rutin50 and Colistin+Rutin100 treatments were found to have therapeutic effects against sciatic nerve injury by decreasing MDA levels and lipid peroxidation, decreasing NF-κB, COX-2, and nNOS levels and inflammation, decreasing GFAP levels, and increasing NCAM levels.
Conclusion: Overall, Rutin was found to have a therapeutic effect against Colistin-induced sciatic nerve injury.

Keywords

Colistin , Rutin , Inflammation , GFAP , NCAM

References

• AbdElrazek, D. A., Hassan, N. H., Ibrahim, M. A., Hassanen, E. I., Farroh, K. Y., & Abass, H. I. (2024). Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats. Food and Chemical Toxicology, 184, 114436.
• Ajiboye, T. O. (2018). Colistin sulphate induced neurotoxicity: Studies on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers. Biomedicine & Pharmacotherapy, 103, 1701-1707.
• Aonurm-Helm, A., Jaako, K., Jürgenson, M., & Zharkovsky, A. (2016). Pharmacological approach for targeting dysfunctional brain plasticity: Focus on neural cell adhesion molecule (NCAM). Pharmacological research, 113, 731-738.
• Arowoogun, J., Akanni, O. O., Adefisan, A. O., Owumi, S. E., Tijani, A. S., & Adaramoye, O. A. (2021). Rutin ameliorates copper sulfate‐induced brain damage via antioxidative and anti‐inflammatory activities in rats. Journal of Biochemical and Molecular Toxicology, 35(1), e22623.
• Cao, J. P., Wang, H. J., Li, L., & Zhang, S. M. (2016). The effects of morphine treatment on the NCAM and its signaling in the MLDS of rats. Drug and Chemical Toxicology, 39(4), 418-423.
• Çelik, H., Kandemir, F. M., Caglayan, C., Özdemir, S., Çomaklı, S., Kucukler, S., & Yardım, A. (2020). Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Molecular biology reports, 47(3), 2023-2034.
• Dai, C., Tang, S., Biao, X., Xiao, X., Chen, C., & Li, J. (2019). Colistin induced peripheral neurotoxicity involves mitochondrial dysfunction and oxidative stress in mice. Molecular Biology Reports, 46(2), 1963-1972.
• Dai, C., Li, M., Sun, T., Zhang, Y., Wang, Y., Shen, Z., Velkov, T., Tang, S., & Shen, J. (2022). Colistin-induced pulmonary toxicity involves the activation of NOX4/TGF-β/mtROS pathway and the inhibition of Akt/mTOR pathway. Food and Chemical Toxicology, 163, 112966.
• Ding, L., Wang, K., Zhu, H., Liu, Z., & Wang, J. (2024). Protective effect of quercetin on cadmium-induced kidney apoptosis in rats based on PERK signaling pathway. Journal of Trace Elements in Medicine and Biology, 82, 127355.
• Dos Reis, B. G., Becker, G. S., Marchetti, D. P., de Moura Coelho, D., Sitta, A., Wajner, M., & Vargas, C. R. (2024). Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment. Metabolic Brain Disease, 40(1), 6.
• Durdu, B., Durdu, Y., Guler, E. M., Kocyigit, A., & Okay, G. (2025). Comparative effects of dexpanthenol and thymoquinone on colistin-induced neurotoxicity in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 1-8.
• Edrees, N. E., Galal, A. A., Monaem, A. R. A., Beheiry, R. R., & Metwally, M. M. (2018). Curcumin alleviates colistin-induced nephrotoxicity and neurotoxicity in rats via attenuation of oxidative stress, inflammation and apoptosis. Chemico-biological interactions, 294, 56-64.
• Er, B., Ozmen, B., Sahin, E., Orhan, C., Sahin, N., Morde, A. A., Padigaru, M., & Sahin, K. (2025). A Novel Ashwagandha (Withania somnifera) Formulation Mitigates Sleep Deprivation-Induced Cognitive Impairment and Oxidative Stress in a Rat Model. Biomolecules, 15(5), 710.
• Eronmosele, J. E., Olurishe, T. O., & Olorukooba, A. B. (2021). Investigation of treatment-time differences in colistin-induced nephrotoxicity in Wistar rats. Chronobiology International, 38(2), 224-233.
• Foudah, A. I., Alqarni, M. H., Alam, A., Devi, S., Salkini, M. A., & Alam, P. (2022). Rutin improves anxiety and reserpine-induced depression in rats. Molecules, 27(21), 7313.
• Gencer, S., Akaras, N., Şimşek, H., Gür, C., İleritürk, M., Küçükler, S., & Kandemir, F. M. (2025). The Protective Effects of Chrysin on Acrylamide‐Induced Hepatotoxicity: Insights Into Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Histological Evaluation in Rats. Journal of Biochemical and Molecular Toxicology, 39(6), e70334.
• Hegab, D. Y., El-Sharkawy, N. I., Moustafa, G. G., Abd-Elhakim, Y. M., Said, E. N., Metwally, M. M., & Saber, T. M. (2025). Pumpkin seeds oil rescues colchicine-induced neurotoxicity in rats via modifying oxidative stress, DNA damage, and immunoexpression of BDNF and GFAP. Tissue and Cell, 94, 102792.
• Jin, T., & Leng, B. (2023). Cynaropicrin averts the oxidative stress and neuroinflammation in ischemic/reperfusion injury through the modulation of NF-kB. Applied Biochemistry and Biotechnology, 195(9), 5424-5438.
• Kandemir, F. M., Ileriturk, M., & Gur, C. (2022). Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular biology reports, 49(7), 6063-6074.
• Kandemir, Ö., İleritürk, M., Gür, C., Akaras, N., Şimşek, H., Yılmaz, S., & Kandemir, F. M. (2025). Carvacrol Coadministration Ameliorates Lambda‐Cyhalothrin‐Induced Peripheral Neuropathy in Rats: Behavioral and Molecular Evidence. Journal of Biochemical and Molecular Toxicology, 39(7), e70400.
• Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S., Akarsu, S. A., & Kandemir, F. M. (2024). Protective effects of naringin on colistin‐induced damage in rat testicular tissue: Modulating the levels of Nrf‐2/HO‐1, AKT‐2/FOXO1A, Bax/Bcl2/Caspase‐3, and Beclin‐1/LC3A/LC3B signaling pathways. Journal of Biochemical and Molecular Toxicology, 38(2), e23643.
• Karaca, O., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Kandemir, Ö., Küçükler, S., Öte Karaca, Ş., & Kandemir, F. M. (2025). Potent Ameliorative Effects of Rosmarinic Acid on Tramadol-Induced Neurotoxicity in the Brain and Hippocampus; by Suppressing Oxidative stress, Apoptosis, ER stress, and Regulating Cognitive Functions. Molecular Neurobiology, 1-19.
• Kessas, K., Lounis, W., Chouari, Z., Vejux, A., Lizard, G., & Kharoubi, O. (2024). Benefits of rutin on mitochondrial function and inflammation in an aluminum-induced neurotoxicity rat model: Potential interest for the prevention of neurodegeneration. Biochimie, 222, 1-8.
• Kumar, J., Haldar, C., & Verma, R. (2021). Melatonin ameliorates LPS-induced testicular nitro-oxidative stress (iNOS/TNFα) and inflammation (NF-kB/COX-2) via modulation of SIRT-1. Reproductive Sciences, 28(12), 3417-3430.
• Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J biol Chem, 193(1), 265-275.
• Okoh, O. S., Akintunde, J. K., Akamo, A. J., & Akpan, U. (2025). Thymoquinone inhibits Neuroinflammatory mediators and vasoconstriction injury via NF-κB dependent NeuN/GFAP/Ki-67 in hypertensive Dams and F1 male pups on exposure to a mixture of Bisphenol-A analogues. Toxicology and Applied Pharmacology, 494, 117162.
• Rahmani, S., Naraki, K., Roohbakhsh, A., Hayes, A. W., & Karimi, G. (2023). The protective effects of rutin on the liver, kidneys, and heart by counteracting organ toxicity caused by synthetic and natural compounds. Food Science & Nutrition, 11(1), 39-56.
• Rajabalizadeh, R., Rahbardar, M. G., Razavi, B. M., & Hosseinzadeh, H. (2024). Renoprotective effects of crocin against colistin-induced nephrotoxicity in a rat model. Iranian Journal of Basic Medical Sciences, 27(2), 151.
• Ramamoorthy, H., Abraham, P., Isaac, B., & Selvakumar, D. (2017). Role for NF-κB inflammatory signalling pathway in tenofovir disoproxil fumarate (TDF) induced renal damage in rats. Food and Chemical Toxicology, 99, 103-118.
• Saafan, S. M., Mohamed, S. A., Noreldin, A. E., El Tedawy, F. A., Elewa, Y. H., Fadly, R. S., Jaouni, S. K. A., El-Far, A., & Alsenosy, A. A. (2023). Rutin attenuates D-galactose-induced oxidative stress in rats’ brain and liver: molecular docking and experimental approaches. Food & Function, 14(12), 5728-5751.
• Shafik, M. S., El-Tanbouly, D. M., Bishr, A., & Attia, A. S. (2023). Insights into the role of PHLPP2/Akt/GSK3β/Fyn kinase/Nrf2 trajectory in the reno-protective effect of rosuvastatin against colistin-induced acute kidney injury in rats. Journal of Pharmacy and Pharmacology, 75(8), 1076-1085.
• Shargh, Z., Asghari, K., Asghariehahari, M., & Chodari, L. (2025). Combined effect of exercise and curcumin on inflammation-associated microRNAs and cytokines in old male rats: A promising approach against inflammaging. Heliyon, 11(2).
• Samir, S. M., Hassan, H. M., Elmowafy, R., ElNashar, E. M., Alghamdi, M. A., AlSheikh, M. H., Al-Zahrani, N. S., Alasiri, F. M., & Elhadidy, M. G. (2024). Neuroprotective effect of ranolazine improves behavioral discrepancies in a rat model of scopolamine-induced dementia. Frontiers in Neuroscience, 17, 1267675.
• Yılmaz, S., Küçükler, S., Şimşek, H., Aygörmez, S., & Kandemir, F. M. (2024). Naringin protects against colistin-induced sciatic nerve damage by reducing oxidative stress, apoptosis and inflammation damage. Journal of Experimental and Clinical Medicine, 41(1), 53-59.
• Yu, W., Zhu, H., Huang, R., Yan, B., Xu, B., Shi, Y., ... & Wang, J. (2024). Roles of Cyt-c/Caspase-9/Caspase-3/Bax/Bcl-2 pathway in Cd-induced testicular injury in rats and the protective effect of quercetin. Toxicon, 237, 107561.
• Zhang, T., Zhang, C., Luo, Y., Liu, S., Li, S., Li, L., Ma, Y., & Liu, J. (2023). Protective effect of rutin on spinal motor neuron in rats exposed to acrylamide and the underlying mechanism. Neurotoxicology, 95, 127-135.
• Zhang, D. Z., Jia, M. Y., Wei, H. Y., Yao, M., & Jiang, L. H. (2024). Systematic review and meta-analysis of the interventional effects of resveratrol in a rat model of myocardial ischemia-reperfusion injury. Frontiers in pharmacology, 15, 1301502.
• Wang, J., Liu, Y. T., Xiao, L., Zhu, L., Wang, Q., & Yan, T. (2014). Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway. Inflammation, 37(6), 2085-2090.