Time-dependent protective effects of Silymarin on renal ischemia-reperfusion injury in rats

Nazim Abdulkadir Kankilic; Tayfun Sahinkanat; Abdulkadir Yasir Bahar; Sefa Resim

doi:10.5281/ zenodo.18636353

Authors

Nazim Abdulkadir Kankilic Aksaray University Faculty of Medicine, Department of Urology, Aksaray, Turkey https://orcid.org/0000-0002-3747-3798
Tayfun Sahinkanat Medline Adana Hospital, Department of Urology, Adana, Turkey https://orcid.org/0000-0001-8128-0275
Abdulkadir Yasir Bahar Kahramanmaras Sutcu Imam University Faculty of Medicine, Department of Pathology, Kahramanmaras, Turkey https://orcid.org/0000-0002-6963-3389
Sefa Resim Kahramanmaras Sutcu Imam University Faculty of Medicine, Department of Urology, Kahramanmaras, Turkey https://orcid.org/0000-0003-1652-4792

DOI:

https://doi.org/10.5281/%20zenodo.18636353

Keywords:

Antioxidant defense system, Oxidative stress, Renal ischemia–reperfusion, Silymarin

Abstract

Objective: Renal ischemia–reperfusion (I/R) injury is a major cause of acute kidney injury observed in surgical and clinical settings such as shock, trauma, partial nephrectomy, and renal transplantation. This study aimed to evaluate the protective effects of silymarin, a flavonolignan complex extracted from Silybum marianum (milk thistle), against renal I/R injury at varying ischemia durations in rats.

Materials and methods: Forty-eight adult male Wistar albino rats were randomly divided into eight groups (n=6 each). The sham group underwent laparotomy only. Control I/R groups were subjected to 45, 60, or 90 minutes of ischemia followed by 180 minutes of reperfusion. Silymarin-treated groups received 100 mg/kg/day silymarin orally for seven days before surgery and underwent the same I/R protocols. At the end of reperfusion, renal tissues and blood samples were collected to determine total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Histopathological evaluation was performed on hematoxylin–eosin–stained sections.

Results: The highest serum TAS and SOD levels were observed in the SIL 45 group, indicating a strong early antioxidant response to silymarin. Serum and tissue MDA levels, indicators of lipid peroxidation, were significantly lower in silymarin-treated groups than in corresponding I/R groups. However, the protective effect decreased as ischemia duration increased. Histopathological analysis revealed less tubular necrosis, vacuolar degeneration, and interstitial congestion in silymarin-treated groups, particularly at shorter ischemia durations.

Conclusion: Silymarin exerts a significant renoprotective effect by enhancing antioxidant capacity and reducing oxidative stress in renal I/R injury. Nevertheless, its efficacy diminishes with prolonged ischemia, suggesting a time-dependent limitation in protection.

References

Tsaroucha AK, Korovesis GN, Valsami G, Lambropoulou M, Kollaras V, Anagnostopoulos C, et al. Silibinin-hydroxypropyl-β-cyclodextrin (SLB-HP-β-CD) complex prevents apoptosis in liver and kidney after hepatic ischemia-reperfusion injury. Food Chem Toxicol. 2020;145:111731.

Gobé G, Willgoss D, Hogg N, Schoch E, Endre Z. Cell survival or death in renal tubular epithelium after ischemia-reperfusion injury. Kidney Int. 1999;56(4):1299-304.

Chatterjee PK. Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review. Naunyn Schmiedebergs Arch Pharmacol. 2007;376(1-2):1-43.

Wu J, Chen H, Li T, et al. Protective effects of antioxidants against renal ischemia-reperfusion injury: experimental evidence and therapeutic potential. Front Pharmacol. 2022;13:847135.

Niu Y, Na L, Feng R, Gong L, Zhao Y, Li Q, et al. The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age-associated inflammation and oxidative stress in healthy rats. Aging Cell. 2013;12(6):1041-9.

Vargas-Mendoza N, Madrigal-Santillán E, Morales-González A, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014;6(3):144-9.

Wang X, Zhang Z, Wu SC. Health benefits of Silybum marianum: Phytochemistry, pharmacology, and applications. J Agric Food Chem. 2020;68(42):11644-64.

Mahi-Birjand M, Karimzadeh I, Zarban A, Abdollahpour-Alitappeh M, Saadatjoo SA, Ziaee M. Protective effects of silymarin on gentamicin-induced nephrotoxicity in infectious patients: a randomized double blinded placebo-controlled clinical trial. Pharm Sci. 2020;26(3):287-95.

Georgiev T, Nikolova G, Dyakova V, Karamalakova Y, Georgieva E, Ananiev J, et al. Vitamin E and silymarin reduce oxidative tissue damage during gentamycin-induced nephrotoxicity. Pharmaceuticals (Basel). 2023;16(10):1365.

Peng P, Zou J, Zhong B, Zhang G, Zou X, Xie T. Protective effects and mechanisms of flavonoids in renal ischemia-reperfusion injury. Pharmacology. 2023;108(1):27-36.

Karimi G, Ramezani M, Tahoonian Z. Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evid Based Complement Alternat Med. 2005;2(3):383-6.

Ayhanci A, Özkal B, Kabay Ş, Burukoğlu Dönmez D, Gül G, Bayramoğlu G, et al. The protective effect of silymarin on the antioxidant system at rat renal ischemia/reperfusion injury model. Afr J Pharm Pharmacol. 2015;7(6):220-6.