Daflon and Centrum Mitigate Vancomycin-Induced Nephrotoxicity in Rats by Ameliorating Oxidative Stress, DNA Damage, Apoptosis, and Inflammation

Hanem F El-Gendy¹Soaad Salamah¹Eman Elhusseiny¹Hazim Khalifa^2*Hossny Elbanna³Taha A Attia¹Shaimaa Selim⁴Saber El Hanbally¹

• ¹University of Sadat City, El Sadat City, Egypt
• ²United Arab Emirates University, Al-Ain, United Arab Emirates
• ³Cairo University, Giza, Egypt
• ⁴Menoufia University, Shebeen El-Kom, Egypt

Vancomycin (VM) is widely used to treat life-threatening infections caused by Gram-positive aerobic and anaerobic bacteria resistant to other antibiotics, but its nephrotoxic effects are a major limitation. This study aimed to evaluate the protective effects of Daflon (DF) and Centrum (CE) against VM-induced nephrotoxicity in male rats by assessing renal DNA damage, histopathological changes, kidney injury biomarkers, inflammatory cytokines, and antioxidant activity. Fifty healthy male Wistar rats were randomly divided into five groups. Group 1 (negative control) received saline intraperitoneally (IP) for 7 days followed by oral distilled water for another 7 days. Group 2 (positive control) received VM (400 mg/kg BW, IP) for 7 days. Group 3 received VM for 7 days followed by oral DF (100 mg/kg BW) for 7 days. Group 4 received VM for 7 days followed by oral CE (15 mg/kg BW) for 7 days. Group 5 received VM for 7 days followed by a combination of DF and CE for the next 7 days. Blood and kidney samples were collected for hematological, biochemical, molecular, comet assay, and histopathological evaluations. Results showed that VM significantly elevated serum creatinine, urea, and uric acid levels (p < 0.01), increased renal malondialdehyde (MDA), and reduced catalase (CAT) and superoxide dismutase (SOD) activities (p < 0.05). Significant histological alterations and increased DNA fragmentation were also observed in the VM group. DF and CE, especially in combination (Group 5), effectively reduced renal damage and DNA fragmentation, with the degree of DNA protection ranked as G5 > G4 > G3 > G2. Additionally, VM increased the expression of PARP1, RIP1, KIM1, TNF-α, and IL-1β, which were significantly downregulated by DF and CE. These agents demonstrated strong antioxidant, anti-inflammatory, and DNA-protective effects. In conclusion, DF and CE mitigated VM-induced nephrotoxicity by reducing oxidative stress, inflammation, and apoptosis, and enhancing antioxidant defenses and DNA repair capacity.