CURCUMIN PREVENTS ADRIAMYCIN-INDUCED NEPHROTOXICITY

XV. CURCUMIN PREVENTS ADRIAMYCIN-INDUCED NEPHROTOXICITY

Nephroxicity is another problem observed in patients who are administered chemotherapeutic agents. Venkatesan et al. showed that curcumin prevents ADR-induced nephrotoxicity in rats (116,121). Treatment with curcumin markedly protected against ADR-induced proteinuria, albuminuria, hypo- albuminemia, and hyperlipidemia. Similarly, curcumin inhibited ADR-in-

duced increase in urinary excretion of N-acetyl-h- D -glucosaminidase (a marker of renal tubular injury), fibronectin, glycosaminoglycan, and plasma

802 Aggarwal et al.

cholesterol. Curcumin restored renal function in ADR-treated rats, as judged by the increase in GFR. The data also demonstrated that curcumin protected against ADR-induced renal injury by suppressing oxidative stress and increasing kidney glutathione content and glutathione peroxidase activity. In like manner, curcumin abolished ADR-stimulated kidney microsomal and mitochondrial lipid peroxidation. These data suggest that administration of curcumin is a promising approach in the treatment of nephrosis caused by ADR.

XVI. CONCLUSION From all these studies, it is clear that curcumin exhibits activities against

cancer, cardiovascular diseases, and diabetes, the major ailments in the United States. This drug has also shown therapeutic effects against Alzhei- mer’s disease, MS, cataract formation, HIV, and drug-induced nonspecific toxicity in the heart, lung, and kidney. Several of the studies establishing curcumin’s potential were carried out in animals. Further testing of curcumin in human is required to confirm these observations. A clinical development plan for using curcumin to treat cancer was recently described by the National Cancer Institute (3).

How curcumin produces its therapeutic effects is not fully understood, but they are probably mediated in part through the antioxidant and anti- inflammatory action of curcumin. It is quite likely that curcumin mediates its effects through other mechanisms as well. More than a dozen different cellular proteins and enzymes have been identified to which curcumin binds. High- throughput, ligand-interacting technology can reveal more molecular targets of curcumin. Microarray gene chip technology may in the future indicate which genes are regulated by curcumin.

ACKNOWLEDGMENT This research was supported by the Clayton Foundation for Research (to

BBA), by Department of Defense of the U.S. Army Breast Cancer Research Program BC010610 (to BBA), and by P50 Head and Neck SPORE grant from National Institute of Health (to BBA). We would like to thank Walter Pagel for a careful review of the manuscript.

ABBREVIATIONS EGF, epidermal growth factor; EGFR, EGF receptor; NF-nB, nuclear

factor-nB; TNF, tumor necrosis factor; H 2 O 2 , hydrogen peroxide; AP-1,

Therapeutic Potential of Curcumin 803

activating protein-1; JNK, c-jun N-terminal kinase; MMP, matrix metal- loprotease; COX, cyclooxygenase; iNOS, inducible nitric oxide synthase; PBMC, peripheral blood mononuclear cells; VSMC, vascular smooth muscle cells; HDL, high-density lipoprotein; TBARS, thiobarbituric acid reactive substance; LDL, low-density lipoprotein; VLDL, very-low density lipopro-

tein; ASA, acetylsalicylic acid; PGI 2 , prostacyclin I 2 ; AA, arachidonic acid; GSH, glutathione; MDA, malondialdehyde; SOD, superoxide dismutase; LDH, lactate dehydrogenase; ISO, isoproterenol; NAG, N-acetyl glucosa-

minidase; TGF-h 1 transforming growth factor beta 1 ; IL, interleukin; MS, multiple sclerosis; CNS, central nervous system; EAE, experimental allergic encephalomyelitis; STAT, signal transducers and activators of transcription; HIV, human immunodeficiency virus; LTR, long terminal repeat; LMW proteins, low-molecular-weight proteins; NSAIDs, nonsteroidal anti-inflam- matory drugs; APP, amyloid precursor; 4-HNE, 4-hydroxy-2-nonenal; GST, gluthathione S-transferase; ADR, Adriamycin; LDH, lactate dehydrogenase; BLM, bleomycin; BAL, bronchoalveolar lavage; ACE, angiotensin-con- verting enzyme; PQ, paraquat.

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