Renal cell damage is associated with lipid peroxide production indicating cell injury due to the production of free radicals. The damage appears due primarily to hyperoxaluria and is augmented by crystal deposition in the renal tubules.

In a previous study we demonstrated that oxalate induced free radical injury can promote calcium oxalate stone formation. In the present study, we tested whether the antioxidants vitamin E, superoxide dismutase (SOD), catalase and desferoxamine (DFO) can provide protection against oxalate toxicity in LLC-PK 1 cells. LLC-PK 1 cells were exposed to oxalate (1.0 mM) or ox-alate+calcium oxalate monohydrate crystals (COM, 500 lgm) for 3, 6, and 9 h. Cellular injury was assessed by lactate dehydrogenase (LDH) release. Malondialdehyde (MDA) content, catalase and glutathione peroxidase activities were also measured. The effect of vitamin E (200 lM), DFO (1.0 mM), SOD (400 U), and catalase (400 U) on oxalate-exposed cells was tested. LLC-PK 1 cells exposed to oxalate showed a significant increase in LDH release and MDA content, which was further elevated when COM crystals were added. Cellular glutathione peroxidase and catalase activities were decreased on exposure to oxalate. The addition of vitamin E, SOD, catalase and DFO significantly reduced the release of LDH and restored glutathione peroxidase and catalase activities towards the control level. The increased formation of MDA on oxalate or oxalate+COM toxicity was restored towards normalization by antioxidants and antioxidant enzymes. The protection rendered by vitamin E was greater than that of SOD, catalase and DFO. We conclude that oxalate associated free radical injury may promote stone formation by providing cellular debris for crystal nucleation and aggregation and augment crystal attachment to other tubular cells. Antioxidant administration may prevent calcium oxalate nucleation and retention in the renal tubules by preventing oxalate mediated peroxidative injury.

radicals and enzymatic activity were then assessed. RESULTSEG treatment in group 1 lead to increased lipid peroxidation, protein thiol, excretion of urinary enzymes, oxalate and decreases in urinary calcium, antioxidant enzymes and altered glutathione redox balance. Although renal function was not altered, there was increased water intake, urine volume and lowered urinary pH in these rats. These changes were more intense, with extensive calcium-oxalate crystal deposition, in rats in group 3, and prevented in rats in group 2, except for urinary oxalate levels, which remained high. Histopathological examination showed that there was no deposition of calcium oxalate crystals in rats in group 2. CONCLUSIONThis is the first study to demonstrate in-vivo evidence that hyperoxaluria-induced peroxidative injury induces individual calcium oxalate crystal attachment in the renal tubules. In addition, excess vitamin E completely prevented calcium oxalate deposition, by preventing peroxidative injury and restoring renal tissue antioxidants and glutathione redox balance. Therefore, vitamin E therapy might provide protection against the deposition of calcium oxalate stones in the kidney of humans.

Activation of survival pathways has been associated with chemoresistance and progression of androgen independence which places a major obstacle to successful treatment of metastatic prostate cancer. Deguelin, a rotenoid isolated from Mundulea sericea, has an anticancer effect against several types of cancers; however, the mechanism of its antitumor effects on prostate cancer is not well understood. The aim of our study was to elucidate the effect of deguelin on the growth of prostate cancer cells and its putative mechanism of action. Deguelin decreased the viability of both androgen-dependent and -independent prostate cancer cells but not normal prostate epithelial cells. Downregulation of phosphorylated Akt and GSK-3b by deguelin promoted proteosomal degradation of b-catenin that resulted in decreased nuclear accumulation and inhibited transactivation of b-catenin-responsive genes. Deguelin-induced downregulation of proliferative (cyclin D1 and c-myc) and antiapoptotic proteins (Mcl-1, Bcl-xL and survivin) in prostate cancer cells culminated in the induction of apoptosis, inhibition of DNA synthesis and cell growth, altered membrane integrity, marked reduction of invasiveness, inhibition of anchorage-dependent and -independent colony formation. Our data demonstrated for the first time that deguelin inhibits the growth and survival of human androgen-independent prostate cancer cells, and its anticancer and antimetastatic activity occurs, at least in part through downregulating GSK-3b/b-catenin signaling pathway and antiapoptotic survival proteins. Taken together our study indicates that deguelin may have translational potential as therapeutic agent for advanced or metastatic prostate cancer.Prostate cancer is the most commonly diagnosed cancer in men, accounting for 30% of all malignant tumors. Men diagnosed with prostate cancer die, most often due to aggressive metastatic disease that fails to respond to hormonal therapy. While hormonal ablation usually works as a first line of treatment against localized tumors, after a few years most patients suffer a relapse when the malignancy becomes androgen independent, resulting in a highly metastatic cancer that is also resistant to both chemotherapy and irradiation.