A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl-2, and HSPs expression

Nutr Cancer. 2011;63(3):427-34. doi: 10.1080/01635581.2011.535958.

Abstract

Cisplatin-induced nephrotoxicity is related to an increase in oxidative stress in the kidney. Lycopene, a carotenoid found in tomatoes, is a potent dietary antioxidant. In the present study, we investigated the effect of the tomato lycopene complex against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Male Wistar rats (n = 28, 8 wk old, between 200-215 g) were divided into 4 groups: (a) control, (b) tomato lycopene complex (6 mg/kg, daily; consisting of 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% β-carotene), (c) cisplatin (7 mg/kg i.p., single dose), and (d) cisplatin + tomato lycopene complex. Cisplatin administration increased serum urea-N (171 vs. 37 mg/dl) and creatinine (1.80 vs. 0.42 mg/dl) and decreased body weight in comparison with the control rats (P < 0.001). Serum creatinine and urea-N levels were lower in rats treated with tomato lycopene complex + cisplatin compared with rats treated with cisplatin alone (P < 0.001). The renal tissue from the cisplatin-treated rats had greater malondialdehyde (MDA; 172 vs. 93 nmol/g) and 8-isoprostane levels (1810 vs. 610 pg/g) than that from the control rats (P < 0.001). Tomato lycopene complex prevented the rise of MDA and 8-isoprostane (P < 0.001). No measurable lycopene could be detected in the serum of the control and cisplatin-treated rats, whereas lycopene was observed in the serum of rats supplemented with tomato lycopene complex. Renal Bax protein expression was significantly higher in the cisplatin-treated rats than in the control rats, and tomato lycopene complex treatment significantly reduced Bax expression (P < 0.001). The expression of Bcl-2 was higher in tomato lycopene complex/cisplatin-treated rats than in the cisplatin-injected rats (P < 0.05). The expression of renal HSP60 and HSP70 was significantly lower in tomato lycopene complex + cisplatin-treated rats than in rats treated with cisplatin alone (P < 0.001). These results suggest that tomato lycopene complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Blood Urea Nitrogen
  • Carotenoids / pharmacology*
  • Cisplatin / toxicity
  • Dinoprost / analogs & derivatives
  • Dinoprost / analysis
  • Down-Regulation
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipid Peroxidation / drug effects
  • Lycopene
  • Male
  • Malondialdehyde / analysis
  • Oxidative Stress / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Solanum lycopersicum / chemistry*
  • Tocopherols / pharmacology
  • Up-Regulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*
  • beta Carotene / pharmacology

Substances

  • Antioxidants
  • Bax protein, rat
  • Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • beta Carotene
  • 8-epi-prostaglandin F2alpha
  • Carotenoids
  • Malondialdehyde
  • phytofluene
  • (all-E) phytoene
  • Dinoprost
  • Cisplatin
  • Tocopherols
  • Lycopene