more, this antioxidant significantly increas-es nitric oxide bioavailability, amelioratingendothelial dysfunction, and attenuates lip-id peroxidation leading to meaningful re-duction in F2-isoprostanes [4, 5]. Thesemolecular mechanisms provide a plausibleexplanation of potential renoprotectivecapacity by inhibition of renal vasocon-striction.

However, someone must take into ac-count the modest acidification of the urineprovoked by vitamin C administration.Even though this effect is mild, lowering ofpH is unfavorable. Another issue of con-flict could be the possible pro-oxidant ac-tion of this vitamin, especially in the pres-ence of free transition metals [4]. Althoughdirect evidence on the occurrence of theseions is lacking, this kind of action appearsto be unlikely in vivo [5].

To our knowledge, vitamin C has notbeen tested in experimental protocols re-garding rhabdomyolysis-induced acute re-nal failure. The favorable effects of this an-tioxidant in various pathophysiological pa-rameters and the excellent safety profileseem to overweigh the previous concerns.We conclude that vitamin C alone, or incombination with other treatments such asalkalinization and metal chelation, deservethorough evaluation in rhabdomyolysis-induced renal dysfunction. Well-designedexperimental protocols in the near futuremay expand our knowledge and elucidateits exact role in this setting.

References

1. Holt SG, Moore KP (2001) Pathogene-sis and treatment of renal dysfunction inrhabdomyolysis. Intensive Care Med 27:803–811

2. Galaris D, Cadenas E, Hochstein P(1989) Redox cycling of myoglobin andascorbate: a potential protective mecha-nism against oxidative reperfusion inju-ry in muscle. Arch Biochem Biophys273:497–504

3. Galaris D, Korantzopoulos P (1997) Onthe molecular mechanism of metmyo-globin-catalyzed reduction of hydrogenperoxide by ascorbate. Free Radic BiolMed 22:657–667

4. Halliwell B, Gutteridge JMC (1999) As-corbic acid (vitamin C). In: Halliwell B,Gutteridge JMC (eds) Free radicals inbiology and medicine, 3rd edn. OxfordUniversity Press, Oxford, pp 200–208

5. Chen K, Suh J, Carr AC, Morrow JD,Zeind J, Frei B (2000) Vitamin C sup-presses oxidative lipid damage in vivo,even in the presence of iron overload.Am J Physiol Endocrinol Metab 279:E1406–1412

P. Korantzopoulos (✉ )Laboratory of Biological Chemistry, University of Ioannina, Medical School,45110 Ioannina, Greecee-mail: pkor@oneway.grTel.: +30-6510-97562Fax: +30-6510-67868

P. Korantzopoulos · D. PapaioannidesDepartment of Medicine, Arta General District Hospital, 47100 Arta, Greece

D. GalarisLaboratory of Biological Chemistry, University of Ioannina, Medical School,45110 Ioannina, Greece

Intensive Care Med (2002) 28:1185DOI 10.1007/s00134-002-1356-9 C O R R E S P O N D E N C E

Panagiotis KorantzopoulosDimitrios GalarisDimitrios Papaioannides

Pathogenesis and treatmentof renal dysfunction in rhabdomyolysis

Received: 15 March 2002Accepted: 15 March 2002Published online: 15 June 2002© Springer-Verlag 2002

Sir: We read with considerable interest therecently published review entitled “Patho-genesis and treatment of renal dysfunctionin rhabdomyolysis” by Holt and Moore [1].The authors clearly stated the importanceof oxidative stress in the pathophysiologyof this disorder and stressed the redox cy-cling of myoglobin as a potential target fortherapeutic manipulations.

Apart from urine alkalinization, specificantioxidant interventions may exert protec-tive effects in rhabdomyolysis by inhibi-tion of myoglobin-induced oxidative dam-age. In particular, vitamin C (ascorbic acid),an outstanding water-soluble antioxidant,has been shown to inhibit effectively theformation of ferryl (Fe4+) myoglobin [2, 3,4]. This oxidized form of myoglobin repre-sents a toxic molecule that triggers oxida-tion reactions such as lipid peroxidation,and is implicated in muscle ischemia-reperfusion injury [2, 4]. Thus vitamin Chas strong theoretical advantage over otherantioxidants in rhabdomyolysis since theabove phenomena contribute substantiallyto muscle and tubular damage. Further-