Biochemical Alterations of Liver Enzymes and Microelements During Leishmania Major Infection in Balb/C Mice after Treatment with Paromomycin

Summary Cutaneous leishmaniasis (CL) is a zoonotic disease caused by Leishmania parasites. CL is still one of the health problems in tropical areas and in Iran. In this study, the Paromomycin was used for treatment of CL in Balb/c mice infected with Leishmania major. It is purposed that Paromomycin can be used as an appropriate achievement for control and therapy of CL. Paromomycin was used to inhibit leishmaniasis in susceptible Balb/c mice infected with Leishmania major MRHO/IR/75/ER; as a prevalent strain of CL in Iran. Serum concentrations of essential trace elements including copper (Cu) and Zinc (Zn) were determined by Flame Atomic Absorption Spectrophotometer (FAAS). Moreover, liver enzymes including Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT) and Alkaline Phosphatase (ALP) were also studied by Auto Analyzer Technical RA1000. Paromomycin therapy caused significant changes in the values of liver enzymes, Zn, Cu and Cu/Zn ratio as observed in healthy and infected Balb/c mice. Although, SGOT, SGPT and Cu were decreased in test groups, Zn and ALP increased in same groups in comparison with controls in healthy and infected groups of mice. The biochemical alteration of trace elements and liver enzymes was indicated during this study, which may attributable to anti-leishmanial effects of Paromomycin injection during L. major infection. This result clarifies Paromomycin as an effective therapy for the treatment of CL in rodent model of leishmaniasis.

[1]  M. Downes,et al.  Hepatobiliary ABC transporters: physiology, regulation and implications for disease. , 2009, Frontiers in bioscience.

[2]  R. Merriman,et al.  Approach to the Patient with Jaundice , 2009 .

[3]  M. Mohebali,et al.  Expression of A2 proteins in amastigotes of Leishmania infantum produced from canine isolates collected in the district of Meshkinshahr, in north–western Iran , 2008, Annals of tropical medicine and parasitology.

[4]  S. Sundar,et al.  Paromomycin in the treatment of leishmaniasis. , 2008, Expert opinion on investigational drugs.

[5]  H. Nahrevanian,et al.  Pharmacological evaluation of anti-leishmanial activity by in vivo nitric oxide modulation in Balb/c mice infected with Leishmania major MRHO/IR/75/ER: an Iranian strain of cutaneous leishmaniasis. , 2007, Experimental parasitology.

[6]  J. El-on,et al.  Leishmania major: in vitro and in vivo anti-leishmanial activity of paromomycin ointment (Leshcutan) combined with the immunomodulator Imiquimod. , 2007, Experimental parasitology.

[7]  F. Ayala,et al.  Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy , 2007, Proceedings of the National Academy of Sciences.

[8]  K Michael Hambidge,et al.  Zinc deficiency: a special challenge. , 2007, The Journal of nutrition.

[9]  M. Panemangalore,et al.  Effect of high dietary zinc on plasma ceruloplasmin and erythrocyte superoxide dismutase activities in Copper-depleted and repleted rats , 1996, Biological Trace Element Research.

[10]  J. Burguera,et al.  Changes in the total content of iron, copper, and zinc in serum, heart, liver, spleen, and skeletal muscle tissues of rats infected withTrypanosoma cruzi , 1993, Biological Trace Element Research.

[11]  A. Fernandes,et al.  Comparative study of the efficacy of formulations containing fluconazole or paromomycin for topical treatment of infections by Leishmania (Leishmania) major and Leishmania (Leishmania) amazonensis , 2007, Parasitology Research.

[12]  M. Davami,et al.  Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: a placebo‐controlled, randomized clinical trial , 2006, Clinical and experimental dermatology.

[13]  M. Davami,et al.  Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of old world cutaneous leishmaniasis: A placebo-controlled, randomized clinical trial , 2006 .

[14]  Sarman Singh,et al.  Transfusion transmitted leishmaniasis: a case report and review of literature. , 2006, Indian journal of medical microbiology.

[15]  A. Fairlamb,et al.  Drug Resistance in Leishmaniasis , 2006, Clinical Microbiology Reviews.

[16]  L. Boscá,et al.  Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. , 2005, Toxicology.

[17]  C. Costa,et al.  Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study , 2004, BMC infectious diseases.

[18]  U. Lindh,et al.  Reduced zinc in peripheral blood cells from patients with inflammatory connective tissue diseases , 1985, Inflammation.

[19]  H. Daniel,et al.  Identification of genes responsive to intracellular zinc depletion in the human colon adenocarcinoma cell line HT-29. , 2004, The Journal of nutrition.

[20]  M. Mohebali,et al.  Alterations of Serum Zinc, Copper and Iron Concentrations in Patients with Acute and Chronic Cutaneous Leishmaniasis , 2003 .

[21]  R. Green,et al.  AGA technical review on the evaluation of liver chemistry tests. , 2002, Gastroenterology.

[22]  J. Louis,et al.  Experimental cutaneous Leishmaniasis: a powerful model to study in vivo the mechanisms underlying genetic differences in Th subset differentiation. , 2002, European journal of dermatology : EJD.

[23]  D. Sereno,et al.  Nitric Oxide-Mediated Proteasome-Dependent Oligonucleosomal DNA Fragmentation in Leishmania amazonensis Amastigotes , 2002, Infection and Immunity.

[24]  H. Nahrevanian,et al.  Nitric oxide and reactive nitrogen intermediates during lethal and nonlethal strains of murine malaria , 2001, Parasite immunology.

[25]  E Westhof,et al.  Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. , 2001, Structure.

[26]  I. Nourmohammadi,et al.  SERUM LEVELS OF ZN, CU, CR AND NI IN IRANIANSUBJECTS WITH ATHEROSCLEROSIS , 2001 .

[27]  T. Kuiken,et al.  Exposure to heavy metals and infectious disease mortality in harbour porpoises from England and Wales. , 2001, Environmental pollution.

[28]  V. Bulut SERUM COPPER, ZINC AND SELENIUM LEVELS IN RHEUMATOID ARTHRITIS , 2001 .

[29]  Nour Zahi Gammoh,et al.  Zinc and the immune system , 2000, Proceedings of the Nutrition Society.

[30]  G. Cremaschi,et al.  Zinc status and immune system relationship: a review. , 2000, Biological trace element research.

[31]  O. Erel,et al.  Effects of antimonial therapy on serum zinc, copper and iron concentrations in patients with cutaneous Leishmaniasis in Turkey. , 1998, Journal of the Egyptian Society of Parasitology.

[32]  E. Carvalho,et al.  Cytokine profile and pathology in human leishmaniasis. , 1998, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[33]  F. Beck,et al.  Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. , 1997, The American journal of physiology.

[34]  S. Croft,et al.  The sensitivity of Leishmania species to aminosidine. , 1995, The Journal of antimicrobial chemotherapy.

[35]  R. Locksley,et al.  The regulation of immunity to Leishmania major. , 1995, Annual review of immunology.

[36]  S. Croft,et al.  Aminosidine ointments for the treatment of experimental cutaneous leishmaniasis. , 1994, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[37]  P. Gangadharam,et al.  In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains , 1994, Antimicrobial Agents and Chemotherapy.

[38]  M. Ulrich,et al.  The clinical and immunological spectrum of American cutaneous leishmaniasis. , 1993, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[39]  A. Albertazzi,et al.  Zinc and cell-mediated immunity in chronic uremia. , 1993, Nephron.

[40]  A. Albertazzi,et al.  Zinc-mediated lymphocyte energy charge modification in dialysis patients. , 1991, ASAIO transactions.

[41]  R. Coffman,et al.  Leishmania major infection in mice: a model system for the study of CD4+ T-cell subset differentiation. , 1991, Research in immunology.

[42]  B. Vallee,et al.  Zinc coordination, function, and structure of zinc enzymes and other proteins. , 1990, Biochemistry.

[43]  M. Hilgartner,et al.  Physiological and Pharmacological Effects of Zinc on Immune Response a , 1990 .

[44]  P. Scuderi,et al.  Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. , 1990, Cellular immunology.

[45]  K. Klasing Nutritional aspects of leukocytic cytokines. , 1988, The Journal of nutrition.

[46]  R. Cousins,et al.  Interleukin-1--stimulated induction of ceruloplasmin synthesis in normal and copper-deficient rats. , 1988, The Journal of nutrition.

[47]  H. Sandstead,et al.  Influence of dietary zinc on rat brain catecholamines. , 1982, The Journal of nutrition.

[48]  A. Grabrucker,et al.  Zinc deficiency , 2000, Archives of disease in childhood.

[49]  R. Neal The effect of antibiotics of the neomycin group on experimental cutaneous leishmaniasis. , 1968, Annals of tropical medicine and parasitology.

[50]  Kellina Oi A study of experimental cutaneous leishmaniasis in white mice , 1961 .

[51]  O. Kellina [A study of experimental cutaneous leishmaniasis in white mice]. , 1961, Meditsinskaia parazitologiia i parazitarnye bolezni.

[52]  S REITMAN,et al.  A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. , 1957, American journal of clinical pathology.