Protective role of zinc picolinate on cisplatin-induced nephrotoxicity in rats.
OBJECTIVE
Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation, oxygen-free radicals, and inflammation in kidney. Zinc is an antioxidant and has anti-inflammatory action. To date, the protective role of zinc picolinate on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the effect of zinc picolinate on cisplatin-induced renal injury.


METHODS
Male Wistar rats (n = 28, 8-week-old, weighing 200 to 220 g) were divided into four groups consisting of 7 rats each: control, zinc picolinate (6 mg Zn kg(-1) BW i.p.), cisplatin (7 mg kg(-1)BW i.p., single dose) and cisplatin plus zinc picolinate.


RESULTS
A single dose of cisplatin resulted in an increase in malondialdehyde, 8-isoprostane, and tumor necrosis factor-α levels of kidney and significantly deranged renal function (urea-N and creatinine; P < .0001). Zinc picolinate treatment significantly reduced urea-N, creatinine, malondialdehyde, 8-isoprostane, and tumor necrosis factor-α -α levels. Concentration of zinc in kidney was increased significantly after zinc picolinate supplementation; however, Fe and Cu levels did not change. Expression of Bax in kidney increased with cisplatin administration, and this could be prevented by zinc picolinate treatment (P < .001). However, bcl-2 expression did not change by zinc or cisplatin treatment (P > .05). The expression of heat shock proteins 60 and 70 in kidney was increased after cisplatin treatment compared with the levels in the control (P < .01), and this increase could be prevented by the zinc picolinate treatment (P < .05).


CONCLUSIONS
These results suggest that zinc picolinate may be a potential preventive agent in cisplatin-induced renal injury through decreasing oxidative stress and inflammation.
Tuzcu
Mehmet
M
Department of Biology, Faculty of Science, Firat University, Elazig, Turkey.
Sahin
Nurhan
N
Dogukan
Ayhan
A
Aslan
Abdullah
A
Gencoglu
Hasan
H
Ilhan
Necip
N
Kucuk
Omer
O
Sahin
Kazim
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D018834:Chaperonin 60 / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010848:Picolinic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C494828:Bax protein, rat; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D010848:Picolinic Acids; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D003404:Creatinine; D015237:Dinoprost; D002945:Cisplatin; C030614:picolinic acid