Antimutageno djelovanje vitamina C na oksidacijske promjene uzrokovane kinolonima

Quinolones are broad-spectrum antibiotics effective against both Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) generated by quinolones may damage cell structures and could be a risk to health. The use of vitamin C to reduce such risks may have the opposite effects: vitamin C in the presence of divalent metal ions can induce the Fenton reaction, leading to hydroxyl radical (HO˙) generation and oxidative damage. The purpose of this study is to evaluate the antioxidant and prooxidant properties of vitamin C by measuring its effects on both lipid peroxidation and mutagenesis induced by quinolones nalidixic acid (NLX) or norfloxacin (NOR) in Salmonella typhimurium TA102. Mutagenicity was evaluated by the Ames test and the results were expressed as (histidine+ revertants/ng of quinolone), while lipoperoxidation was measured as thiobarbituric acid reactive substances (μmol malondialdehyde/(mL·h)). The effects of different concentrations of nalidixic acid (10–1000 ng) or norfloxacin (7–700 ng) on S. typhimurium TA102 were studied, employing the S9 mix (liver homogenate from rats pre-treated with Arochlor 1254) in the presence of 10–1000 μg of ascorbic acid (AA) with 0.1 mM FeCl3 or EDTA. Minimal inhibitory concentrations of NOR and NLX against 25 uropathogenic Escherichia coli strains were obtained using the plate dilution method in the presence of vitamin C. Vitamin C (1 mg) together with 0.1 mM FeCl3 showed a prooxidant effect in the S9 mix and enhanced the lipoperoxidation induced by either NOR or NLX. Mutagenic potency was also increased for both NOR and NLX. When metal ions were chelated with EDTA, ascorbate showed both antimutagenic and antioxidant properties. Mutagenic potency and lipoperoxidation were reduced for both NOR and NLX. The addition of vitamin C did not change the minimal in vitro inhibitory concentrations of NLX or NOR against the 25 uropathogenic E. coli strains. The antimutagenic and antioxidant effects of vitamin C were especially marked when the Salmonella strain was exposed to NOR or NLX in the presence of EDTA. In contrast, the vitamin C in the presence of FeCl3 increased ROS generation, enhancing both the mutagenic effect of the quinolones and malondialdehyde production from lipoperoxidation induced in the bacterial membranes. Therapeutic use of quinolones together with vitamin C and divalent cations might induce the Fenton reaction involving norfloxacin and nalidixic acid. However, our results suggest that vitamin C could be a good alternative for reducing the genotoxic risk of these therapeutic drugs if it is carefully handled.Kinoloni su antibiotici širokog spektra koji djeluju na Gram-pozitivne i Gram-negativne bakterije. Stvaraju reaktivne metabolite kisika što mogu oštetiti strukturu stanica i time narušiti zdravlje ljudi. Da bi se taj rizik smanjio, koristi se vitamin C koji međutim može imati i suprotno djelovanje: u prisutnosti dvovalentnih iona metala potiče Fentonovu reakciju, što dovodi do stvaranja hidroksil radikala (HO˙) koji oštećuju stanicu. Svrha je ovoga rada utvrditi antioksidativna i prooksidativna svojstva vitamina C ispitivanjem njegova utjecaja na peroksidaciju lipida i mutagenezu induciranu kinolonima poput nalidiksinske kiseline i norfloksacina iz soja bakterije Salmonella typhimurium TA102. Mutagenost je procijenjena Amesovim testom, a rezultati su izraženi kao broj revertanata histidin+/ng kinolona. Peroksidacija lipida mjerena je reakcijom produkata s tiobarbiturnom kiselinom, te izražena kao μmol malonaldehida/(mL·h). Istražen je utjecaj različitih koncentracija nalidiksinske kiseline (10-1000 ng) ili norfloksacina (7-700 ng) na bakteriju S. typhimurium TA102 pomoću mješavine S9 (homogenat jetre štakora tretiranih aroklorom 1254), 10-1000 μg vitamina C i 0,1 mM FeCl3 ili etilendiamintetraoctene kiseline (EDTA). Najmanje koncentracije norfloksacina i nalidiksinske kiseline, potrebne za inhibiciju 25 uropatogenih sojeva bakterije Escherichia coli, određene su metodom na agaru u prisutnosti vitamina C. Vitamin C (1 mg) uz 0,1 mM FeCl3 imao je prooksidativno djelovanje u mješavini S9, pospješio je peroksidaciju lipida uzrokovanu norfloksacinom ili nalidiksinskom kiselinom, te pojačao mutagenost oba kinolona. Stvaranje kelatnog kompleksa iona metala s EDTA potaknulo je antimutageno i antioksidativno djelovanje vitamina C, te smanjilo mutageno i lipoperoksidacijsko djelovanje norfloksacina i nalidiksinske kiseline. Dodatak vitamina C nije smanjio minimalnu koncentraciju nalidiksinske kiseline i norfloksacina in vitro, potrebnu za inhibiciju 25 uropatogenih sojeva bakterije E. coli. Antimutageno i antioksidativno djelovanje vitamina C bilo je osobito izraženo kada je soj bakterije Salmonella izložen djelovanju norfloksacina ili nalidiksinske kiseline u prisutnosti EDTA. Zajedno s FeCl3 vitamin C je ubrzao stvaranje reaktivnih metabolita kisika, pojačavajući time mutageno djelovanje kinolona te proizvodnju malondialdehida peroksidacijom lipida u membrani bakterija. Uporaba kinolona u kombinaciji s vitaminom C i dvovalentnim kationima pri liječenju bolesti mogla bi pokrenuti Fentonovu reakciju s norfloksacinom i nalidiksinskom kiselinom. Međutim, rezultati autora pokazuju da bi se vitamin C, pravilnom primjenom, mogao upotrijebiti kako bi se smanjila opasnost od genotoksičnog djelovanja tih lijekova

Antimutagenicity of Methanolic Extracts from Anemopsis californica

Anemopsis californica has been used empirically to treat infectious diseases. However, there are no antimutagenic evaluation reports on this plant. The present study evaluated the antioxidant activity in relation to the mutagenic and antimutagenic activity properties of leaf (LME) and stem (SME) methanolic extracts of A. californica collected in the central Mexican state of Querétaro. Antioxidant properties and total phenols of extracts were evaluated using DPPH (1,1-diphenyl-2-picrylhydrazyl) and Folin-Ciocalteu methods, respectively. Mutagenicity was evaluated using the Ames test employing Salmonella enterica serovar Typhimurium strains (TA98, TA100, and TA102), with and without an aroclor 1254 (S9 mixture). Antimutagenesis was performed against mutations induced on the Ames test with MNNG, 2AA, or 4NQO. SME presented the highest antioxidant capacity and total phenolic content. None of the extracts exhibited mutagenicity in the Ames test. The extracts produced a significant reduction in 2AA-induced mutations in S. typhimurium TA98. In both extracts, mutagenesis induced by 4NQO or methyl-N′-nitro-N-nitrosoguanidine (MNNG) was reduced only if the exposure of strains was <10 μg/Petri dish. A. californca antioxidant properties and its capacity to reduce point mutations render it suitable to enhance medical cancer treatments. The significant effect against antimutagenic 2AA suggests that their consumption would provide protection against carcinogenic polycyclic aromatic compounds

Prospective study of urinary tract infection surveillance after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>Urinary tract infection (UTI) remains one of the main complications after kidney transplantation and it has serious consequences.</p> <p>Methods</p> <p>Fifty-two patients with kidney transplantation were evaluated for UTI at 3-145 days (mean 40.0 days) after surgery.. Forty-two received a graft from a live donor and 10 from a deceased donor. There were 22 female and 30 male patients, aged 11-47 years. Microscopic examinations, leukocyte esterase stick, and urinary culture were performed every third day and weekly after hospitalization. A positive culture was consider when patients presented bacterial counts up to 10⁵ counts.</p> <p>Results</p> <p>UTI developed in 19/52 (37%) patients at 3-75 days (mean 19.5 days after transplantation. Recurrent infection was observed in 7/52 (13.4%) patients at days 17-65. UTI was more frequent in patients who received deceased grafts compared with live grafts (7/10, 70% <it>vs</it>. 12/42, 28%; p < 0.007). Female patients were more susceptible than male (11/22, 50% <it>vs</it>. 8/22, 36.35%; p < 0.042). Five-year survival rate was 94.5% (49/52 patients). Kidney Graft exit update is 47/52 (90.2%), and there were no significant differences between graft rejection and UTI (p = 0.2518). Isolated bacteria were <it>Escherichia coli </it>(31.5%), <it>Candida albicans </it>(21.0%) and <it>Enterococcus </it>spp. (10.5%), followed by <it>Pseudomonas aeruginosa, Klebsiella pneumoniae, Morganella </it><it>morganii, Enterobacter cloacae </it>and <it>Micrococcus </it>spp. Secondary infections were produced by (7/19, 36.8%). <it>Enterococcus </it>spp. (57%), <it>E. coli </it>(28%) and <it>Micrococcus </it>spp. (14.2%). Antibiotic resistance was 22% for ciprofloxacin and 33% for ampicillin. Therapeutic alternatives were aztreonam, trimethoprim-sulfamethoxazole, netilmicin and fosfomycin.</p> <p>Conclusions</p> <p>Surveillance of UTI for the first 3 months is a good option for improving quality of life of kidney transplantation patients and the exit of graft function especially for female patients and those receiving deceased grafts. Antibiograms provided a good therapeutic alternative to patients who presented with UTIs after receiving a kidney allograft.</p

Etiología de la infección cérvico vaginal en pacientes del Hospital Juárez de México

Objetivo. Conocer la etiología de la infección cérvico vaginal, con el fin de establecer un diagnóstico acertado que permita ofrecer a las pacientes el tratamiento más apropiado. Material y métodos. De enero de 1995 a diciembre de 1999 se realizó un estudio bacteriológico a 6 811 muestras de exudado cérvico vaginal de pacientes del Hospital Juárez de México, de la Ciudad de México, con edades comprendidas entre los 13 y los 65 años, que referían leucorrea, prurito, hiperemia y dolor abdominal bajo. Resultados. La frecuencia de infección por cada germen fue G vaginalis, 22.65%, Candida spp, 19.13%, C albicans, 7.8%, T vaginalis, 1.5%, Streptococcus del grupo D, 11.78%, Streptococcus b haemolyticus, 4.59%, E coli, 13.46%, Klebsiella ssp, 2.0%, además de otras enterobacterias menos frecuentes como Citrobacter spp, Enterobacter spp, Pseudomonas spp, M morganii y P mirabilis. El 2.9% presentó anaerobios siempre asociados con G vaginalis. Se aislaron Neisseria spp y N weaveri en 0.15% de las muestras. La N gonorrhoeae no se encontró en ningún caso. Datos comparativos indican que, tanto Streptococcus hemoliticos como E coli tuvieron un marcado incremento en los dos últimos años, siendo el de esta última estadísticamente significativo (p<0.001). El método de ji cuadrada se aplicó para la evaluación de los datos. Conclusiones. Considerando la diversidad de la etiología de la infección se recomienda realizar cultivos de la secreción cérvico vaginal a todas las pacientes con sintomatología sugestiva de ella. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htm

Antiamoebic and Toxicity Studies of a Carbamic Acid Derivative and Its Therapeutic Effect in a Hamster Model of Hepatic Amoebiasis

Amoebiasis is an important public health problem in developing countries. Entamoeba histolytica, the causative agent of amoebiasis, may develop resistance to nitroimidazoles, a group of drugs considered to be the most effective against this parasitic disease. Therefore, research on new drugs for the treatment of this common infection still constitutes an important therapeutic demand. In the present study we determined the effects of a carbamate derivative, ethyl 4-chlorophenylcarbamate (C4), on trophozoites of E. histolytica strain HM-1:IMSS. C4 was subject to various toxicity tests, including the determination of mutagenicity for bacterial DNA and changes in the enzymatic activities of eukaryotic cells. Genotoxicity studies were performed by the mutagenicity Ames test (plate incorporation and preincubation methods) with Salmonella enterica serovar Typhimurium, with or without metabolic activation produced by the S9 fraction of rat liver. C4 toxicity studies were performed by measuring enzymatic activity in eukaryotic cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-formazan test with Fischer 344 rat hepatocytes. C4 did not induce either frame-shift mutations in S. enterica serovar Typhimurium TA97 or TA98 or base pair substitutions in strains TA100 and TA102. The compound was not toxic for cultured rat hepatic cells. Trophozoites treated with 100 μg of C4 per ml were inhibited 97.88% at 48 h of culture; moreover, damage to the amoebae was also confirmed by electron microscopy. The antiamoebic activity of C4 was evaluated by using an in vivo model of amoebic liver abscess in hamsters. Doses of 75 and 100 mg/100 g of body weight reduced the extent of the amoebic liver abscess by 84 and 94%, respectively. These results justify further studies to clearly validate whether C4 is a new suitable antiamoebic drug

In vitro and in vivo antifungal activity, liver profile test, and mutagenic activity of five plants used in traditional Mexican medicine

Berberis hartwegii Benth., Berberidaceae, Hamelia patens Jacq., Rubiaceae, Dendropanax arboreus (L.) Decne & Planch., Araliaceae, Erythrina herbacea L., Fabaceae, and Zanthoxylum caribaeum Lam., Rutaceae, acetone extracts were selected on the basis of their use in traditional Mexican medicine to treat scabies or skin diseases. Anti-dermatophyte activity in vitro was evaluated using the agar dilution assay, and the therapeutic efficacy of B. hartwegii and Z. caribaeum were tested against experimental tinea pedis. The infected animals were treated intragastrically daily for seven days with 2.5 and 5 mg/kg of acetone extracts. The acetone extract of H. patens exhibited 100% growth inhibition against T. mentagrophytes and E. floccosum at 100.0 and 50.0 µg/ml, respectively, and B. hartwegiiinhibited growth of M. canis and T. mentagrophytes at 100.0 µg/ml. Effective treatments with 2.5 mg/kg of Z. caribaeum and B. hartwegii extract were comparable with 1 mg/kg of clotrimazole in mice. Liver profile tests and histological analyses did not exhibit any signs of toxicity and the Ames test indicated that both extracts were safe when evaluated in strains TA98, TA100 and TA102. Our results suggest the potential for the future development of new antifungal drugs from B. hartwegii or Z. caribaeum

Antimutagenic Effects of Vitamin C Against Oxidative Changes Induced by Quinolones

Quinolones are broad-spectrum antibiotics effective against both Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) generated by quinolones may damage cell structures and could be a risk to health. The use of vitamin C to reduce such risks may have the opposite effects: vitamin C in the presence of divalent metal ions can induce the Fenton reaction, leading to hydroxyl radical (HO˙) generation and oxidative damage. The purpose of this study is to evaluate the antioxidant and prooxidant properties of vitamin C by measuring its effects on both lipid peroxidation and mutagenesis induced by quinolones nalidixic acid (NLX) or norfloxacin (NOR) in Salmonella typhimurium TA102. Mutagenicity was evaluated by the Ames test and the results were expressed as (histidine+ revertants/ng of quinolone), while lipoperoxidation was measured as thiobarbituric acid reactive substances (μmol malondialdehyde/(mL·h)). The effects of different concentrations of nalidixic acid (10–1000 ng) or norfloxacin (7–700 ng) on S. typhimurium TA102 were studied, employing the S9 mix (liver homogenate from rats pre-treated with Arochlor 1254) in the presence of 10–1000 μg of ascorbic acid (AA) with 0.1 mM FeCl3 or EDTA. Minimal inhibitory concentrations of NOR and NLX against 25 uropathogenic Escherichia coli strains were obtained using the plate dilution method in the presence of vitamin C. Vitamin C (1 mg) together with 0.1 mM FeCl3 showed a prooxidant effect in the S9 mix and enhanced the lipoperoxidation induced by either NOR or NLX. Mutagenic potency was also increased for both NOR and NLX. When metal ions were chelated with EDTA, ascorbate showed both antimutagenic and antioxidant properties. Mutagenic potency and lipoperoxidation were reduced for both NOR and NLX. The addition of vitamin C did not change the minimal in vitro inhibitory concentrations of NLX or NOR against the 25 uropathogenic E. coli strains. The antimutagenic and antioxidant effects of vitamin C were especially marked when the Salmonella strain was exposed to NOR or NLX in the presence of EDTA. In contrast, the vitamin C in the presence of FeCl3 increased ROS generation, enhancing both the mutagenic effect of the quinolones and malondialdehyde production from lipoperoxidation induced in the bacterial membranes. Therapeutic use of quinolones together with vitamin C and divalent cations might induce the Fenton reaction involving norfloxacin and nalidixic acid. However, our results suggest that vitamin C could be a good alternative for reducing the genotoxic risk of these therapeutic drugs if it is carefully handled