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

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.

Sub-acute toxicity study of a new aminoglycoside etimicin sulphate in swiss albino mice.

Etimicin sulfate, an ethylization derivative of gentamicin, is a new soluble wide-spectrum synthetic aminoglycoside drug. It has wide antibacterial spectrum with high effect and less cross resistance as compared to other aminoglycosides. In order to further explore its safety and tolerance, we have conducted a subactute toxicity study on swiss albino mice. Results from the present study have elucidated that treatment of etimicin sulfate exerts no significant signs of toxicity at any dose level used in the study. Physiological as well as hematological parameters were unaltered throughout the study. Biochemical examination and histopathology of all organs confirmed no significant alteration at any dose levels. The result of this study has suggested there was no obvious toxicity observed with the treatment of etimicin sulphate. It was found to be a safe alternative for various severe infections.

Pharmacokinetic study of sulbactomax.

We have evaluated pharmacokinetics of a fixed dose combination (FDC) of ceftriaxone and sulbactam (2:1) or sulbactomax in eight healthy volunteers. A 1.5 g dose of sulbactomax, 1 g dose of ceftriaxone and 0.5 g sulbactam were given intravenously in a balanced two-ways cross-over study. Serially collected plasma sample was analyzed for ceftriaxone and sulbactam by high performance liquid chromatography (HPLC). The mean peaks of ceftriaxone and sulbactam concentrations in plasma were 152.06+/-6.65 microg/ml and 21.32+/-1.80 microg/ml, respectively and plasma half-lives for ceftriaxone and sulbactam were 5.2+/-0.35 hr and 0.94+/-0.038 hr, respectively. The AUC0-24 for ceftriaxone and sulbactam was 760.16+/-27.68 microg.hr/ml and 20.74+/-2.34 microg.hr/ml, respectively, with elimination rate constant of 0.133+/-0.009 hr(-1) and 0.732+/-0.029 hr(-1), respectively. The kinetics of ceftriaxone and sulbactum did not change in combination as compared to the alone treatment. Also, concentration of the ceftriaxone after 24 hr is higher than the minimum inhibitory concentration (MIC) of the most of the gram positive and gram negative bacteria indicating that one dose in a day is sufficient to treat the disease caused by these organisms.

Ceftriaxone-vancomycin drug toxicity reduction by VRP 1020 in Mus musculus mice.

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.

Fixed dose combination of cefepime plus amikacin prevent oxidative stress in liver of Mus musculus mice.

Oxidative stress and free radical are causative factors for aminoglycoside induced tissue injury. The objective of present study was to evaluate effect of fixed dose combination of cefepime + amikacin on antioxidant enzymes such as superoxide dismutase (SOD), catalase along with malonaldialdehyde (MDA) levels in liver of Mus musculus mice. Our findings showed that the activities of the antioxidant enzymes such as superoxide dismutase (p<0.001, 62.2%), catalase (p<0.05, 47.5%) were significantly lowered along with increase in the MDA levels (66.0%) after the single treatment of amikacin as compared to control group. A significant improvement in the activities of superoxide dismutase and catalase along with decrease in MDA levels were observed in fixed dose combination of cefepime plus amikacin treated groups as compared to amikacin alone treated group. These findings suggest that the fixed dose combination therapy of cefepime + amikacin (Potentox) show significant free radical scavenging property which may contribute to decrease in aminoglycoside induced liver injury.