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01 March 2007

Effect of carnosine on gentamicin-induced nephrotoxicity

Kawther M. Soliman, Manal Abdul-Hamid, Amel I. Othman

Med Sci Monit 2007; 13(3): BR73-83 :: ID: 475524

Abstract

Background: Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Thus the present study was undertaken to investigate if carnosine, an antioxidant, could protect the kidney in this experimental model.
Material/Methods: The animals were divided into seven groups each of 10 animals: one control group, two healthy carnosine groups (10 mg/kg/day), two GM groups (80 mg/kg/day), and two carnosine-GM groups.
Kidney function tests, histopathological, ultrastructural, and enzymatic histochemical studies clarified GM nephrotoxicity.
Results: GM rat showed early kidney function failure as blood creatinine and blood urea were signifi cantly increased after one and two weeks. Experimental evidence suggested a role of reactive oxygen species
in GM-induced nephrotoxicity. Histopathological examination revealed degenerative changes in glomeruli and tubules. Ultrastructural study showed glomerular changes, some degeneration of both distal and collecting tubules. The proximal tubules showed marked degrees of changes and
necrosis. Enzymatic histochemical studies of GM rats revealed marked elevation of lactate dehydrogenase (LDH) and inhibition of succinic dehydrogenase (SDH), alkaline phosphatases (ALP), acid phosphatases (ACP), and adenosine triphosphatase (ATPase). Blood creatinine and urea were normalized in the carnosine-GM group after one and two weeks. Structural and enzymatic histochemical pictures were greatly ameliorated.
Conclusions: The mechanism by which carnosine has a protective effect on GM-induced nephrotoxicity was attributed to its many actions: double antioxidant action, protein molecule protection, removal of harmfully modifi ed ones, activation of immune system, preservation of membrane fl uidity, and cytosolic buffering. Carnosine thus offers a promise of ameliorating GM nephrotoxicity.

Keywords: Enzymes - metabolism, Carnosine - pharmacology, Animals, Gentamicins - toxicity, Kidney Diseases - physiopathology, Kidney Function Tests, Kidney Glomerulus - ultrastructure, Rats

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