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Silybum marianum (milk thistle) improves vancomycin induced nephrotoxicity by downregulating apoptosis
Naila Malkani1, Ammara Naeem2, Farah Ijaz2
1Department of Zoology, GC University, Lahore, Pakistan. nailamalkani@gcu.edu.pk.
Abstract:
Increased use of vancomycin for treating infections, and the associated risk of causing nephrotoxicity lead to the present study. The antioxidant and anti-apoptotic potential of Silybum marianum is used along with vancomycin to reduce adverse effects on the kidney. Vero cells (monkey kidney cells) and mice were used to test S. marianum extract on vancomycin induced nephrotoxicity. Vero cells were treated with different concentrations of vancomycin and S. marianum for 24 h for determination of cytotoxic potential and mRNA levels of apoptotic genes p53 , p21, and cyt-c were measured. For in-vivo studies mice were divided into five groups; G1 control (untreated), G2 vehicle (olive oil), G3 vancomycin treated (300 mg/kg body weight), G4 (S. marianum; 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight simultaneously) and G5 (S. marianum 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight treatment started after day 4 of S. marianum treatment). After 10 days histopathological analysis of mice kidneys was performed, serum urea and creatinine were analysed and mRNA expression of p53 , p21, and cyt-c was evaluated. Expression of p53, p21, and cyt-c in Vero cells was elevated in response to vancomycin treatment, whereas after S. marianum administration expression of these genes reduced. Vancomycin showed apoptosis in cells at the concentration of 6 mg/ml (LC50). Urea and creatinine levels in mice were increased in response to vancomycin administration and kidney histology showed an abnormality in functional units. The apoptotic cells were very visible in kidney structure in vancomycin treated group. These symptoms were however relieved in groups where treatment of S. marianum extract was given. mRNA expression of p53 , p21, and cyt-c also reduced in S. marianum treated groups of mice. S. marianum extract has protective effects against renal damage from vancomycin induced oxidative stress and relieves symptoms may be by downregulating apoptotic genes.
Insights
Silybum marianum extract protects against vancomycin-induced kidney damage by reducing oxidative stress and downregulating apoptotic genes. This study demonstrates its potential therapeutic benefits in preventing nephrotoxicity.
Area of Science:
- Pharmacology and Toxicology
- Natural Product Chemistry
- Renal Physiology
Background:
- Vancomycin is crucial for treating infections but poses a significant risk of nephrotoxicity.
- Oxidative stress and apoptosis are key mechanisms in vancomycin-induced kidney damage.
- Silybum marianum (milk thistle) possesses known antioxidant and anti-apoptotic properties.
Purpose of the Study:
- To investigate the protective effects of Silybum marianum extract against vancomycin-induced nephrotoxicity.
- To evaluate the impact of Silybum marianum on apoptotic gene expression and kidney function markers in vitro and in vivo.
Main Methods:
- In vitro: Vero cells treated with vancomycin and Silybum marianum; assessed cytotoxicity and mRNA levels of p53, p21, and cyt-c.
- In vivo: Mice divided into control, vancomycin-treated, and Silybum marianum co-treated groups.
- Evaluated kidney histopathology, serum urea/creatinine levels, and apoptotic gene expression (p53, p21, cyt-c) in mice.
Main Results:
- Vancomycin elevated apoptotic gene expression (p53, p21, cyt-c) and induced cell death in Vero cells.
- Vancomycin treatment in mice increased serum urea and creatinine, with observable kidney damage and apoptosis.
- Silybum marianum administration significantly reduced vancomycin-induced nephrotoxicity, normalized kidney function markers, and decreased apoptotic gene expression.
Conclusions:
- Silybum marianum extract demonstrates significant protective effects against vancomycin-induced nephrotoxicity.
- The protective mechanism may involve the downregulation of pro-apoptotic genes and mitigation of oxidative stress.
- Silybum marianum shows potential as an adjunct therapy to reduce vancomycin-related kidney adverse effects.
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