Ceftriaxone-Vancomycin Drug Toxicity Reduction by VRP 1020 in Mus musculus Mice

Arvind      Soni; Manu      Chaudhary; Vivek   Kumar   Dwivedi

doi:10.2174/157488409788185025

Abstract

Drug toxicity is a common cause of liver injury and kidney failure. This study was designed to elucidate whether administration of high doses of Ceftriaxone or Vancomycin induce oxidative stress in liver as well as kidney, and to investigate the protective effects of VRP 1020 with fixed dose combination of ceftriaxone-vancomycin (Immunox-V). Twenty four Mus musculus mice (weighing 30 ± 5 g) were divided into four groups containing six mice in each group. The activities of antioxidant enzymes such as superoxide dismutase, catalase and the level of malonaldialdehyde, as an marker of lipid per oxidation, were measured to evaluate oxidative stress in homogenates of the liver and renal tissue. Ceftriaxone or vancomycin administration significantly increased malonaldialdehyde levels (p < 0.001) but significant decreased in superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Co-administration of VRP 1020 with FDC of Immunox-V injections caused significantly decreased malonaldialdehyde levels (p < 0.001) and increased superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver and renal tissue when compared with other treated groups. Similarly, the levels of extracellular antioxidant (Creatinine and Uric acid) were found to be significant lowered in Immunox-V treated group when compared to ceftriaxone or vancomycin alone treated group. These results indicate that chemical mediated technology of VRP 1020 with fixed dose combination of Immunox-V can prevent drug induced nephrotoxicity and oxidative stress which protects liver injury as well as renal tissue damage by reducing reactive oxygen species which improve the activities of free radical scavenging enzymes.

Keywords: Ceftriaxone, vancomycin, fixed dose combination, VRP1020, antioxidant enzymes, free radical, malonaldialdehyde

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