The investigation of effects of oxolamine on doxorubicin induced experimental renal damage

ABSTRACT THE INVESTIGATION OF EFFECTS OF OXOLAMINE ON DOXORUBICIN INDUCED EXPERIMENTAL RENAL DAMAGE Doxorubicin is an anthracycline derivative and is antineoplastic agents. Clinical effectiveness is restricted due to dose-limiting toxic side effects. Toxic side effects is seen in cardiac, renal and liver. Oxolamine is a antitussive agent. Oxolamine also possesses analgesic, antiinflammatory, local anaesthetic and antispasmodic properties. The aim of present study was to investigate the effects of oxolamine in doxorubicine induced kidney injury. Twentyfour adult, male Wistar albino rats were used and were divided into four groups: I, control (n=6); II, doxorubicin (n=6); III, doxorubicine+oxolamine, (n=6); IV, oxolamine (n=6). In the doxorubicin group; the animals were treated with single dose 15 mg/kg/i.p. doxorubicin. In the doxorubicin+oxolamine group; the animals were treated with single dose 15 mg/kg/i.p. doxorubicin and also during experiment rats are treated oxolamine 50 mg/kg/i.p. dose per day total 7 day. In the oxolamine group were treated with oxolamine 50 mg/kg/i.p. dose per day during experiment. After administration of the drugs, the rats were decapitated and their kidneys were removed and fixed in 10% neutral buffered formalin. Tissue samples were stained with H&E (Hematoxylin-Eosin) and histological examined with light microscopy. Apoptosis was evaluated with TUNEL staining. MDA levels were evaluated with spectrophotometric method. Immunohistochemical stain is done for ASIC3, MMP-2, MMP-9 and investigate by light microscopy. Both glomerular and tubular apoptotic index in doxorubicin group was significantly higher than the control group (p<0.05). Glomerular and tubular apoptotic index in doxorubicin+oxolamine group was lower than doxorubicin group. Renal tissue MMP-2, MMP-9 and ASIC3 levels in doxorubicin group was significantly higher comparared to control group. Renal tissue MMP-2, MMP-9 and ASIC3 levels in doxorubicin+oxalamine group was significantly lower comparared to doxorubicin group. As a result giving oxolamine to doxorubicin applied rats can provide positive effects in preventing the development of doxorubicin nephrotoxicity via significantly lowering renal tissue MMP-2, MMP-9 and ASIC3 levels and also apoptotic index. Key words: Doxorubicin, oxolamine, ASIC3, MMP-2, MMP-9