Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model

Abstract

We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid peroxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.

Synergistic protective role of ceftriaxone and ascorbic acid against subacute diazinon-induced nephrotoxicity in rats

“…6 Renal TNF-a levels in the control and the different treated groups. Different letters mean statistical significance at P B 0.05 according to oneway ANOVA followed by Tukey's Range Test for post hoc analysis 1998; Dwivedi et al 2012). Pre-treatment with AA might play a role in reducing the toxic effect of DZN, and its powerful antioxidant properties seem to mediate such a protective effect, indicated by the reduction of MDA as well as the elevation of GSH, GSH-Px, SOD, CAT and TAC levels in renal tissue Ashrafi et al 2012;Rehman et al 2012;Saleem et al 2012).…”

“…Other non-antibiotic actions of CTX on animal studies demonstrated that it could ameliorate morphine tolerance (Rawls et al 2010b), and dependence (Rawls et al 2010a), diabetic hyperalgesia (Gunduz et al 2011) and neuropathic pain (Liu et al 2010). Moreover, CTX attenuate cyclosporine A (Yilmaz et al 2011), tobramycin (Beauchamp et al 1994), isepamicin (Yoshiyama et al 1998), and cadmiuminduced (Dwivedi et al 2012) nephrotoxicity in rats.…”

Unravelling Pathophysiology of Crystalline Nephropathy in Ceftriaxone-Associated Acute Kidney Injury: A Cellular Proteomic Approach

“…In addition, further studies on the effects of “soluble” ceftriaxone on renal tubular cells would be of interest to better understand the pathophysiology of ceftriaxone-associated AKI. Note that the soluble ceftriaxone exhibited non-antimicrobial protective effects in models of neurological diseases, that is, Alexander’s disease [33, 34], Parkinson’s disease [35], and early brain injury after subarachnoid hemorrhage [36] and nephrotoxicity due to deltamethrin insecticide [37] and cadmium metal [38]. It is suspected that renal tubular cells would recognize and respond to soluble ceftriaxone and Cef-Ca crystals differently, and possession of this knowledge may have translational potentials in pediatric precision medicine.…”

Synergistic protective effects of ceftriaxone and ascorbic acid against subacute deltamethrin-induced nephrotoxicity in rats

“…Other non-antibiotic pharmacodynamic effects of CTX on animal studies demonstrated that it could reduce morphine tolerance and dependence 13 , ameliorate diabetic hyperalgesia 14 , and diminish neuropathic pain 15 . Moreover, CTX attenuated nephrotoxicity in rats induced by cadmium 16 , cyclosporine A 17 , tobramycin 18 , and isepamicin 19 .…”