ISSN : 2146-3123
E-ISSN : 2146-3131

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats
Seda Yakut1, Tuğçe Atcalı2, Cüneyt Çaglayan3, Aykut Ulucan4, Fatih Mehmet Kandemir5, Adem Kara6, Turgut Anuk7
1Department of Histology and Embryology, Burdur Mehmet Akif Ersoy University Faculty of Veterinary Medicine, Burdur, Türkiye
2Department of Physiology, Bingöl University Faculty of Veterinary Medicine, Bingöl, Türkiye
3Department of Biochemistry, Bilecik Şeyh Edebali University Faculty of Medicine, Bilecik, Türkiye
4Department of Medical Services and Techniques, Bingöl University, Vocational School of Health Services, Bingöl, Türkiye
5Department of Biochemistry, Aksaray University Faculty of Medicine, Aksaray, Türkiye
6Department of Molecular Biology and Genetics, Erzurum Technique University Faculty of Science, Erzurum, Türkiye
7Clinic of General Surgery, University of Health Sciences Türkiye, Erzurum Regional Training and Research Hospital, Erzurum, Türkiye
DOI : 10.4274/balkanmedj.galenos.2024.2024-1-60
Pages : 193-205

Abstract

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits.
Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways.
Study Design: Experimental animal model.
Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/ kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models.
Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05).
Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

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