Hamid Salari

Elimination of Salmonella contamination from poultry tissues by cetylpyridinium chloride solutions

The effects of cetylpyridinium chloride (CPC) on the inhibition and reduction of viable Salmonella typhimurium cells were studied. In these experiments skin excised from chicken drumsticks was treated with solutions of CPC. At the CPC concentrations used, the ability of this compound to reduce bacterial contamination was clearly demonstrated. This effect was both CPC concentration- and exposure-time-dependent. A 4.87-log reduction of viable S. typhimurium cells was achieved at a CPC concentration of 4 mg/ml at the treatment time of 3 min. Moreover, CPC was effective in preventing bacterial contamination, as shown by a 4.9-log inhibition of S. typhimurium cell attachment at a CPC concentration of 8 mg/ml and a treatment time of 10 min.

Copper-, iron-, manganese- and zinc-3,5-diisopropylsalicylate complexes increase survival of gamma-irradiated mice

Eighty μmol/kg of copper(II)2(3,5-diisopropylsalicylate)4(H2O)2 [Cu(II)2(3,5-DIPS)4] given subcutaneously (sc) to female mice 24 h before lethal (LD10030) irradiation was found to allow 58% survival. Subsequent studies using LD5030 irradiations revealed that 80 or 92% survival was obtained in female or male mice, respectively, when 20 μmol/kg was given 3 h before irradiation; 88–92% survival was achieved in female mice treated with 2.5, 5, or 10 μmol/kg 3 h after irradiation; and 75 or 95% of the male mice survived when they had been given 50 μmol/kg orally 24 or 4 h, respectively, before irradiation. Using LD5030 irradiations it was also found that administration of 280 μmol of Fe(III)-(3,5-DIPS)3(H2O)/kg led to 84% survival in male mice; 80 μmol of Mn(II)-(3,5-DIPS)2(H2O)/kg allowed 96 or 100% survival in male or female mice, respectively; and 60 μmol Zn(II)-(3,5-DIPS)2/kg achieved 95% survival in male mice. In addition, all of these complexes were found to have anti-convulsant activities suggesting possible protection against radiation-induced seizures. It is concluded that these essential metalloelement complexes have radiation-protection and radiation-recovery activities and that their use represents a physiological approach to preventing or perhaps predominantly facilitating recovery from radiation injury.

Copper(II)(3,5‐Diisopropylsalicylate)2 Accelerates Recovery of B and T Cell Reactivity Following Irradiation

Copper(II)(3,5‐diisopropylsalicylate)2 (Cu‐DIPS), administered subcutaneously to mice at 80 mg/kg body weight, bad marked radioprotective activity. Given 3 h before exposure to 8.0 Gy (800 rad) irradiation. Cu‐DIPS increased the 42‐day survival from 40% to 86%. Seven days after exposure to 8.0 Gy, there were severe reductions in spleen weight (73%) and cellularity (98%) in both Cu‐DIPS‐and vehicle‐treated mice. Viable spleen cells collected 7 days after irradiation were totally unresponsive to mitogenic or antigenic stimulation regardless of Cu‐DIPS or vehicle treatment, suggesting that Cu‐DlPS did not prevent radiation‐induced damage to mature lymphocytes. At 14 days, when Cu‐DIPS‐treated mice started to show improved survival over vehicle‐treated mice, spleen weights and cellularity were 2.5‐ and 3.5‐fold higher, respectively, in Cu‐DIPS‐treated mice. Treatment with Cu‐DIPS not only enhanced splenic repopulation. but also accelerated the reappearance of both B and T cell reactivities. Spleen cell responsiveness to the B cell mitogen, lipopolysaccharide (LPS), and the T cell mttogen, concanavalin A (Con A), regenerated significantly faster in Cu‐DIPS‐treated mice. Cu‐DIPS also significantly accelerated the regeneration of T‐dependent antibody induction. Based on these assays of immunocompetence, Cu‐DIPS‐treated mice had, on average, a seven‐fold greater capacity to respond to immune stimulation than vehicle‐treated mice 24 days after irradiation.

Radiation Recovery Agents: Cu(II), Mn(II), Zn(II), OR Fe(III) 3,5-Diisopropylsalicylate Complexes Facilitate Recovery from Ionizing Radiation Induced Radical Mediated Tissue Damage

Pathological consequences of human exposure to increasing doses of ionizing radiation: Hematopoietic, Gastrointestinal, and Central Nervous System syndromes, are rather well understood.1 Bone marrow aplasia and loss of immunocompetency with low (2 to 10 Gray) doses of irradiation, gastrointestinal ulceration and systemic infection with higher radiation doses, and loss of brain function with still higher doses account for the diminishing duration of survival following exposure to increasing doses of ionizing radiation.

High-performance liquid chromatography determination of residue levels on chicken carcasses treated with cetylpyridinium chloride.

Cetylpyridinium chloride (CPC) has been found to be effective in reducing contamination of chicken carcasses from a variety of microorganisms, including Escherichia coli O157:H7, Salmonella typhimurium, Campylobacter jejuni, Aeromonas hydrophila, Listeria monocytogenes, and Staphylococcus aureus. A procedure has been developed to determine residue levels on chicken carcasses after CPC treatment. For the analysis, chicken carcasses were extracted with 95% ethanol. The CPC concentration in the extract was measured by high-performance liquid chromatography (HPLC) with ultraviolet detection using dodecylpyridinium chloride (DPC) as an internal standard. The method was validated in the concentration range of 3-200 microg/ml CPC in ethanolic extract. This assay is rapid, precise, and accurate.

Bioavailable Copper Complexes Offer a Physiologic Approach To Treatment Of Chronic Diseases

Copper (II)2(3,5-Diisopropylsalicylate)4(H2O)2 has been found to have antiinflammatory, antiulcer, anticonvulsant, anticancer, anticarcinogenic, antimutagenic, and radiation recovery activities and it prevents reperfusion injury. To study pharmacokinetic parameters accounting for these pharmacological effects the double labeled 67Cu(II)2(carboxy-14C-3,5-diisopropylsalicylate)4 complex was synthesized and used to obtain these parameters. Treatment of mice with 1 mumol of this complex revealed that 67Cu was distributed to blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, brain, urine, and feces within 0.5 hr and patterned changes in 67Cu content of these tissues and excreta were found throughout the 96 hr term of this study.

Pharmacokinetic distribution of 67Cu(II)2[3,5-diisopropyl(carboxy-14C)salicylate]4 among murine tissues.

Non-toxic doses of tetrakis-mu-3,5-diisopropylsalicylatodicopper(II) [Cu(II)2(3,5-DIPS)4] have been found to have anti-inflammatory, analgesic, anti-ulcer, anti-colitis, anti-convulsant, anti-cancer, anti-mutagenic, anti-carcinogenic, and anti-diabetic activities and, in addition, facilitates recovery from lethal irradiation and ischemia-reperfusion injuries. The goal of this research was to determine the time-dependent tissue distribution and persistence of 67Cu and the 14C labeled salicylate ligand, carboxy-14C-3, 5-diisopropylsalicylate [3,5-DIP(carboxy-14C)S], following subcutaneous administration of a 50 micromole per kilogram of body mass dose of double labeled tetrakis-mu-3,5-diisopropyl[carboxy-14C]salicylatodiaquo [67Cu]dicopper(II) 67Cu(II)4[3,5-DIP(carboxy-14C)S]4. This compound was administered to nine groups of six 20 gram female C57BL/6 mice and blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, and brain tissues removed and analyzed for 67Cu and 14C at 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after treatment. These data were then analyzed using a pharmacokinetic model simulation program. Both 67Cu and 14C were found in all tissues as well as urine and feces at 0.5 hour after administration. As anticipated, 67Cu entered the liver storage pool; it was conserved by the kidneys, and subsequently underwent release in maintaining 67Cu levels in all other tissues. While the presence of 67Cu correlated with the presence of the salicylate ligand, 3,5-DIP (carboxy-14C)S, early in the course of this experiment, the ligand was lost via ligand exchange and could not be measured in blood, kidney, intestine, lung, thymus, spleen, and brain after 24 hours following administration. However, 3,5-DIP(carboxy-14C)S persisted in liver, femur, and muscle throughout the 5-day period of study. It is suggested that marked lipophilicity accounts for its very rapid distribution to all tissues wherein it undergoes ligand exchange as 67Cu is incorporated into Cu-dependent enzymes and proteins and persists in tissues based upon physiological demand for Cu in meeting normal biochemical requirements.

Anticancer Effects of Cu(II)(3,5-Diisopropylsalicylate)2in Mice Inoculated Intramuscularly with Ehrlich Ascites Carcinoma Cells

In 1979, Oberley and Buettner published a review1 which suggested that all neoplastic cells were deficient in total superoxide dismutase (SOD) activity. To determine whether or not Cu-Zn SOD had an anticancer effect, Oberley and Leuthauser injected mi ce wi th a single dose of this enzyme one hour after they implanted Sarcoma 180 tumor cells in the hind limb of CF1 mice and measured average leg diameter versus time after implantation. In animals treated with saline, tumor growth was unimpeded.2 Animals treated with Cu-Zn SOD showed a reduction in tumor growth. Animals treated with Cu-Zn SOD also showed a slight increase in survival in comparison to those treated only with saline-vehicle.

Radioprotectant Effects of Cu(II)(3,5-DIPS)2

Ionizing radiation of oxygenated aqueous solution is known to produce superoxide as a secondary product of radiation,1–3 Part of the cellular injuries caused by radiation can be attributed to the acute increase of superoxide. Addition of Cu-Zn superoxide dismutase (Cu-Zn SOD) to the extracellular medium can significantly protect cultured cells against radiation damage.4 Adding Cu-Zn SOD to cultures of myoblasts protected them from a radiation-induced decrease in viability and altered morphology5 as well as chromosomal damage.6

Accelerated Recovery of Immunocompetent with Radioprotective Cu-DIPS

Copper(II)(3,5-diisopropylsalicylate)2 (Cu-DIPS) provided substantial radioprotectant activity when administered 3 hours prior to exposure to gamma irradiation1. The present study investigated immune parameters of Cu-DIPS-mediated radioprotectant activity. It was found that Cu-DIPS did not prevent the destruction of mature lymphocytes, but accelerated the recovery of both the numbers of cells in the spleen and the responsiveness of those cells.