Nrf2/HO-1 signaling pathway may be the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene.
Cisplatin is used against various types of solid tumors. However, its use is limited by its nephrotoxicity, with about 25-35% patients experiencing a significant decline in renal function after a single dose of cisplatin. This study reports that lycopene mitigates the nephrotoxic effect of cisplatin in rat through Nrf2-mediated induction of heme oxygenase-1 (HO-1). Eight weeks old male rats (200-215 g) were supplemented with lycopene complex containing 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% beta-carotene for 10 days at a dose level of 6 mg/kg bw, followed by a single i.p. injection of cisplatin (7 mg/kg bw). Western blot analysis of renal Nrf2, HO-1 and NF-kappaB p65 showed that cisplatin-induced decrease in the levels of Nrf-2 and HO-1 was counteracted by lycopene. On the other hand, cisplatin mediated increase in NF-kappaB p65 was brought down by lycopene. Lycopene supplementation is reported to significantly improve the changes associated with cisplatin nephrotoxicity, as also evident by increased level of antioxidant enzymes. The study suggests that Nrf2/HO-1 signaling pathway may be the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene, and reduces inflammation by inhibiting NF-kappaB. Correlation between NF-kappaB and Nrf2 is discussed.
Sahin
Kazim
K
Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey. nsahinkm@yahoo.com
Tuzcu
Mehmet
M
Sahin
Nurhan
N
Ali
Shakir
S
Kucuk
Omer
O
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000077276:Lycopene; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D051996:Transcription Factor RelA; D002338:Carotenoids; D051547:Heme Oxygenase-1; D005978:Glutathione; D002945:Cisplatin; D000077276:Lycopene