Panax notoginseng saponins attenuated cisplatin-induced nephrotoxicity.
OBJECTIVE
To study protective effects of Panax notoginseng saponins (PnS) against cisplatin-nephrotoxicity.


METHODS
Cisplatin-induced nephrotoxicity in mice in vivo, and primary culture of rabbit proximal tubular cells (PTC) in vitro were established. Blood urea nitrogen, serum creatinine, cell viability, DNA interstrand cross-link, DNA-protein cross-link, and cytosolic free [Ca2+]i were assayed with diacetyl monoxime, alkaline picrate, trypan blue, ethidium bromide binding, 125I-postlabelling, and Fur 2-AM, respectively.


RESULTS
With pretreatment for 2 d in mice, PnS 100 and 200 mg.kg-1.d-1 suppressed cisplatin-induced high blood urea nitrogen level to 83% and 31%, and serum creatinine level to 86% and 42%, respectively (P < 0.01). Preincubated with PTC for 24 h, PnS 10 and 100 mg.L-1 inhibited cisplatin-induced decrease of cell viability from 78% to 81% (P < 0.05) and 89% (P < 0.01), respectively. PnS 10 and 100 mg.L-1 suppressed formations of DNA interstrand cross-link to 47% and 40%, DNA-protein interstrand cross-link to 77% and 42%, and cytosolic free [Ca2+]i overload in PTC to 70% and 63%, respectively. (P < 0.01).


CONCLUSIONS
PnS was a prophylactic for cisplatin-induced nephrotoxicity, and mechanisms were relevant to the effects that PnS reduced cisplatin-induced cytosolic free [Ca2+]i overload, and formations of DNA interstrand cross-link and DNA-protein cross-link.
Liu
S J
SJ
Department of Clinical Pharmacology, Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China.
Zhou
S W
SW
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001806:Blood Urea Nitrogen; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D036145:Ginsenosides; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D005894:Panax; D010946:Plants, Medicinal; D011817:Rabbits; D011897:Random Allocation; D012503:Saponins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D036145:Ginsenosides; D012503:Saponins; D004247:DNA; D003404:Creatinine; C035054:ginsenoside Rg1; D002945:Cisplatin