Pyrolidium dithiocarbamate prevents shockwave lithotripsy-induced renal injury through inhibition of nuclear factor-kappa B and inducible nitric oxide synthase activity in rats.

ABSTRACT

PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is commonly used for treatment of renal stones. Free oxygen radicals are involved in the pathophysiology of renal injury due to SWL. We investigated the protective effect of pyrolidium dithiocarbamate (PDTC), an antioxidant and nuclear factor kappa-B (NFkappa-B) inhibitor, against renal injury. MATERIALS AND METHODS: Forty-eight rats were divided into three groups group 1, controls; group 2, SWL (15 kW, 1500 pulses); and group 3, SWL + pyrolidium dithiocarbamate (PDTC) (100 mg/kg/day given intraperitoneally 1 day before and 5 days after SWL). The rats were sacrificed and their kidneys were removed on days 7 and 35 after SWL. Samples were fixed in formaldehyde solution, and renal tissues were examined for proximal tubular injury under light microscopy. iNOS activity and active subunit of NFkappa-B, p65, were evaluated immunohistochemically using rat monoclonal antibodies interpreting results semiquantitatively. RESULTS: There were significant differences between SWL and control groups on days 7 and 35, considering histological changes under light microscope (p < 0.02). There was significant decrease in necrosis and fibrosis in PDTC group compared to SWL group. Expression of inducible nitric oxide synthase (iNOS) and p65 on days 7 and 35 were at basal levels as seen with immunohistochemical staining. There were high concentrations of iNOS and p65 in the SWL group (P < 0.02). No significant difference in concentrations was seen between the control and the PDTC groups (P > 0.02). CONCLUSION: We found that curcumin decreased the expression of iNOS, p65, and serum nitric oxide levels, and helped prevent interstitial, glomerular, tubular epithelial, and endothelial cellular injury. We believe that PDTC could be used, particularly in high-risk patients, as a protective agent against renal injury due to SWL.