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Panax notoginseng saponins attenuated cisplatin-induced nephrotoxicity
1Department of Clinical Pharmacology, Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China.
Aim:
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).
Conclusion:
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.
Insights
Panax notoginseng saponins (PnS) protect against cisplatin-induced kidney damage by reducing cellular damage and DNA cross-linking. This study shows PnS as a potential prophylactic agent for preventing nephrotoxicity.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Cisplatin is a widely used chemotherapy drug.
- Cisplatin administration can lead to severe kidney damage (nephrotoxicity).
- Identifying protective agents against cisplatin-induced nephrotoxicity is crucial for patient care.
Purpose of the Study:
- To investigate the protective effects of Panax notoginseng saponins (PnS) against cisplatin-induced nephrotoxicity.
- To elucidate the underlying mechanisms of PnS in mitigating kidney damage.
Main Methods:
- In vivo study using cisplatin-induced nephrotoxicity in mice.
- In vitro study using primary rabbit proximal tubular cells (PTC).
- Assays included blood urea nitrogen, serum creatinine, cell viability, and DNA cross-linking measurements.
Main Results:
- PnS pretreatment significantly reduced blood urea nitrogen and serum creatinine levels in mice.
- PnS increased cell viability in PTC exposed to cisplatin.
- PnS suppressed the formation of DNA interstrand cross-links and DNA-protein cross-links.
Conclusions:
- Panax notoginseng saponins (PnS) demonstrate significant prophylactic effects against cisplatin-induced nephrotoxicity.
- The protective mechanisms involve reducing cytosolic free calcium overload and inhibiting DNA cross-linking.
- PnS represents a promising therapeutic strategy for preventing chemotherapy-induced kidney damage.