Abstract
The aim of this study was to evaluate the efficiency of methylene blue (MB) in preventing renal scar formation after the induction of pyelonephritis (PNP) in a rat model with delayed antimicrobial therapy. An inoculum of the K-12 strain of Escherichia coli was injected into both kidneys. Control groups received isotonic saline instead of bacterial solution. Four equal groups were then formed: the PNP group was untreated and the PNP ciprofloxacin (CIP) treated group was treated only with CIP intraperitoneally (i.p.) starting on the third day following bacterial inoculation. In the PNP (MB)-treated group, MB was given i.p., and in the PNP MB + CIP-treated group, MB + CIP were administered i.p.. In the sixth week following bacterial inoculation, all rats were sacrificed, and both kidneys of the rats in all groups were examined biochemically and histopathologically for renal scarring. Renal scar was significant in the groups treated with MB alone or MB + CIP combination compared with untreated or antibiotic only groups. Delayed treatment with antibiotics had no effect on scarring. These results suggest that the addition of MB to the delayed antibiotic therapy might be beneficial in preventing PNP-induced oxidative renal tissue damage.
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Abbreviations
- PNP:
-
pyelonephritis
- CIP:
-
ciprofloxacin
- MB:
-
methylene blue
- XO:
-
xanthine oxidase
- DMSA:
-
dimercaptosuccinic acid
- NADPH:
-
nicotinamide adenine dinucleotide phosphate
- HP:
-
hydroxyproline
- MDA:
-
malondialdehyde
- NO:
-
nitric oxide
- SOD:
-
superoxide dismutase
- CAT:
-
catalase
- iNOS:
-
inducible nitric oxide synthase
- NOS:
-
nitric oxide synthase
- PMNs:
-
polymorphonuclear leukocytes
- i.p.:
-
intraperitoneally
- UT:
-
untreated
- SC:
-
sham control
References
Jakobsson B, Berg U, Svensson L (1994) Renal scarring after acute pyelonephritis. Arch Dis Child 70:111–115
Brown P, Ki M, Foxman B (2005) Acute pyelonephritis among adults: cost of illness and considerations for the economic evaluation of therapy. Pharmacoeconomics 23:1123–1142
Majd M, Rushton HG, Jantausch B, Wiedermann BL (1991) Relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection. J Pediatr 119:578–585
Slotki IN, Asscher AW (1982) Prevention of scarring in experimental pyelonephritis in the rat by early antibiotic therapy. Nephron 30:262–268
Glauser MP, Lyons JM, Braude AI (1978) Prevention of chronic experimental pyelonephritis by suppression of acute suppuration. J Clin Invest 61:403–407
McLorie GA, McKenna PH, Jumper BM, Churchill BM, Gilmour RF, Khoury AE (1990) High grade vesicoureteral reflux: analysis of observational therapy. J Urol 144:537–545
Talan DA, Stamm WE, Hooton TM, Moran GJ, Burke T, Iravani A, Reuning-Scherer J, Church DA (2000) Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial. JAMA 283:1583–1590
Talan DA, Naber KG, Palou J, Elkharrat D (2004) Extended-release ciprofloxacin (Cipro XR) for treatment of urinary tract infections. Int J Antimicrob Agents 23 (Suppl 1):54–66
Roberts JA, Roth JK Jr, Domingue G, Lewis RW, Kaack B, Baskin G (1982) Immunology of pyelonephritis in the primate model. V. Effect of superoxide dismutase. J Urol 128:1394–1400
Kaur A, Garg UC, Sethi AK, Gorowara S, Sharma S, Ganguly NK (1988) Effect of various oxygen free radical scavengers in preventing tissue injury caused by E. coli in pyelonephritic mice. Biochem Int 16:1083–1093
Meylan PR, Markert M, Bille J, Glauser MP (1989) Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring. Infect Immun 57:2196–2202
Gupta R, Gupta S, Joshi K, Ganguly NK (1997) Role of iron and iron chelation therapy in oxygen free radical mediated tissue injury in an ascending mouse model of chronic pyelonephritis. Comp Immunol Microbiol Infect Dis 20:299–307
Gupta R, Verma I, Sharma S, Ganguly NK (2004) Prevention of tissue injury in an ascending mouse model of chronic pyelonephritis-role of free radical scavengers. Comp Immunol Microbiol Infect Dis 27:225–234
Salaris SC, Babbs CF, Voorhees WD 3rd (1991) Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury. Biochem Pharmacol 42:499–506
Kelner MJ, Bagnell R, Hale B, Alexander NM (1988) Potential of methylene blue to block oxygen radical generation in reperfusion injury. Basic Life Sci 49:895–898
Kelner MJ, Bagnell R, Hale B, Alexander NM (1988) Methylene blue competes with paraquat for reduction by flavo-enzymes resulting in decreased superoxide production in the presence of heme proteins. Arch Biochem Biophys 262:422–426
Andresen M, Dougnac A, Diaz O, Hernandez G, Castillo L, Bugedo G, Alvarez M, Dagnino J (1998) Use of methylene blue in patients with refractory septic shock: impact on hemodynamics and gas exchange. J Crit Care 13:164–168
Deutsch SI, Rosse RB, Schwartz BL, Fay-McCarthy M, Rosenberg PB, Fearing K (1997) Methylene blue adjuvant therapy of schizophrenia. Clin Neuropharmacol 20:357–363
Kupfer A, Aeschlimann C, Cerny T (1996) Methylene blue and the neurotoxic mechanisms of ifosfamide encephalopathy. Eur J Clin Pharmacol 50:249–252
Marczin N, Ryan US, Catravas JD (1992) Methylene blue inhibits nitrovasodilator- and endothelium-derived relaxing factor-induced cyclic GMP accumulation in cultured pulmonary arterial smooth muscle cells via generation of superoxide anion. J Pharmacol Exp Ther 263:170–179
Clinical and Laboratory Standards Institute (2006) Performance standards for antimicrobial susceptibility testing; sixteenth informational supplement. Wayne Pa USA M100-S16
Yagmurlu A, Boleken ME, Ertoy D, Ozsan M, Gokcora IH, Dindar H (2003) Preventive effect of pentoxifylline on renal scarring in rat model of pyelonephritis. Urology 61:1037–1041
Rezzani R, Rodella L, Corsetti G, Bianchi R (2001) Does methylene blue protect the kidney tissues from damage induced by ciclosporin A treatment? Nephron 89:329–336
Pohl HG, Rushton HG, Park JS, Chandra R, Majd M (1999) Adjunctive oral corticosteroids reduce renal scarring: the piglet model of reflux and acute experimental pyelonephritis. J Urol 162:815–820
Kivirikko KI, Laitinen O, Prockop DJ (1967) Modifications of a specific assay for hydroxyproline in urine. Anal Biochem 19:249–255
Ohkawa H, Oshishi N, Yagi K (1979) Assay of lipid peroxidation in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358
Lowry OH, Rosenbrough NJ, Farr AC, Randall RJ (1951) Protein measurement with the folin phenol regent. J Biol Chem 193:265–275
Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500
Aebi H (1984) Catalase in vitro assay methods. Methods Enzymol 105:121–126
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138
Rushton HG, Majd M, Chandra R, Yim D (1988) Evaluation of 99m technetium dimercaptosuccinic acid renal scans in experimental acute pyelonephritis in piglets. J Urol 140:1169–1174
Majd M, Rushton HG, Chandra R, Andrich MP, Tardif CP, Rashti F (1996) Technetium 99m-DMSA renal cortical scintigraphy for the detection of experimental acute pyelonephritis in piglets: comparison of planar (pinhole) and SPECT imaging. J Nucl Med 37:1731–1734
Wikstad I, Hannerz L, Karlsson A, Eklof AC, Olling S, Aperia A (1990) 99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats. Pediatr Nephrol 4:331–334
Bennett RT, Mazzaccaro RJ, Chopra N, Melman A, Franco I (1999) Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats. J Urol 161:1681–1684
Huang A, Palmer LS, Hom D, Anderson AE, Kushner L, Franco I (1999) Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol 162:1396–1398
Mundi H, Bjorksten B, Svanborg C, Ohman L, Dahlgren C (1991) Extra cellular release of ROS from human neutrophils upon interaction with E. coli strain causing renal scarring. Infect Immun 59:4168–4172
Matsumoto T, Mitzunoe Y, Ogata N, Tanaka M, Takahashi K, Kumazawa J (1992) Antioxidant effect on renal scarring following infection of mannose-sensitive-piliated bacteria. Nephron 60:210–215
Bille J, Glauser MP (1982) Protection against chronic pyelonephritis in rats by suppression of acute suppuration: effect of colchicine and neutropenia. J Infect Dis 146:220–226
Haraoka M, Matsumoto T, Mizunoe Y, Ogata N, Takahashi K, Kubo S, Tanaka M, Kumazawa J (1993) Effect of prednisolone on renal scarring in rats following infection with Serratia marcescens. Ren Fail 15:567–571
Matsumoto T, Haraoka M, Mizunoe Y, Takahashi K, Kubo S, Sakumoto M, Tanaka M, Kumazawa J (1995) Preventive effect of ulinastatin on renal scarring in rat model of pyelonephritis induced by direct or ascending infection with Serratia marcescens or Escherichia coli. Nephron 69:65–70
Roberts JA (1992) Vesicoureteral reflux and pyelonephritis in the monkey: a review. J Urol 148:1721–1725
Shimamura T (1981) Mechanisms of renal tissue destruction in an experimental acute pyelonephritis. Exp Mol Pathol 34:34–42
Cook HT, Smith J, Salmon JA, Cattell V (1989) Functional characteristics of macrophages in glomerulonephritis in the rat. 02-Generation, MHC class II expression, and eicosanoid synthesis. Am J Pathol 134:431–437
Miller T, Phillips S (1981) Pyelonephritis: the relationship between infection, renal scarring and antimicrobial therapy. Kidney Int 19:654–662
Risdon RA (1994) Pyelonephritis and reflux nephropathy. In: Tisher CC, Brenner BM (eds) Renal pathology with clinical and functional correlations, 2nd edn. Lippincott, Philadelphia, pp 842–854
Poljakovic M, Svensson ML, Svanborg C, Johansson K, Larsson B, Persson K (2001) Escherichia coli–induced inducible nitric oxide synthase and cyclooxygenase expression in the mouse bladder and kidney. Kidney Int 59:893–904
Glynne PA, Picot J, Evans TJ (2001) Coexpressed nitric oxide synthase and apical beta (1) integrins influence tubule cell adhesion after cytokine-induced injury. J Am Soc Nephrol 12:2370–2383
Mayer B, Brunner F, Schmidt K (1993) Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol 45:367–374
Ignarro LJ, Harbison RG, Wood KS, Kadowitz PJ (1986) Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: stimulation by acetylcholine, bradykinin and arachidonic acid. J Pharmacol Exp Ther 237:893–900
Coddington CC, Anderson TL, Accetta CR, Swanson J, Kruger T, Hodgen GD (1989) Adverse effects of methylene blue on human sperm motility, components of human reproductive tract fluids, and mouse embryo cleavage. Fertil Steril 51:480–485
Donnelly ET, Lewis SE, Thompson W, Chakravarthy U (1997) Sperm nitric oxide and motility: the effects of nitric oxide synthase stimulation and inhibition. Mol Hum Reprod 3:755–762
Coleman MD, Coleman NA (1996) Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf 14:394–405
Larsson SH, Aperia A (1991) Renal growth in infancy and childhood—experimental studies of regulatory mechanisms. Pediatr Nephrol 5:439–442
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Aksu, B., Inan, M., Kanter, M. et al. The effects of methylene blue on renal scarring due to pyelonephritis in rats. Pediatr Nephrol 22, 992–1001 (2007). https://doi.org/10.1007/s00467-007-0464-8
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DOI: https://doi.org/10.1007/s00467-007-0464-8