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Title: Assessment of Rats Exposed to a Novel Polymyxin B Formulation (VRP-034) Following Polymyxin B-Induced Kidney Injury
Abstract: Despite playing a crucial part in the treatment of gram-negative infections that are life-threatening, Polymyxin-clinical B’s utility is constrained by the possibility of acute kidney injury. In response, a novel polymyxin-B formulation is being created to lessen drug-induced kidney damage. Using kidney injury biomarkers in rats, we evaluated the toxicity of four variations of that novel formulation (VRP034 F21-F24) in this study compared to polymyxin-B standard. Polymyxin-B (control) or one of the four polymyxin-B formulations were given subcutaneously to Sprague-Dawley rats at a dose of 25 mg/kg/day (HED: 4 mg/kg/day) over the course of two days. To identify serum biomarkers, serum samples were taken at baseline and at the end of day 2. On day 2, a necropsy was performed, and a kidney was collected for histopathological analysis. When compared to baseline values, all biomarkers in the control group showed a statistically significant increase (p 0.0001) on day 2 [urea: 311%; creatinine: 700%; KIM-1: 180%; cystatin-C: 66%] and 50% of the animals died (one after the 7th dose and two after the 8th dose) prior to the necropsy that was planned. In contrast, neither a significant increase in any of the biomarkers nor any mortality was noticed in animals treated with novel formulations. In contrast to the control group, only minor tubular damage was observed in two formulation groups (VRP034 F21, F24), and no significant damage was found in the other two groups (VRP034 F22-23). Histopathology of the control group kidney confirmed necrotic changes in tissues with congestion and vacuolization. The risk of polymyxin-induced kidney damage in rats was significantly decreased by the novel polymyxin-B formulation tested in this study.
Keywords: drug-induced kidney injury; polymyxin B; acute kidney injury; KIM-1; nephrotoxicity; cystatin-C; biomarkers
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Antibiotics
Writer Experience: 20+ Years
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