| Cisplatin,whose full name is cis-1,2-dichlorodiamine platinum,is currently one of the most effective and commonly used anti-tumor drugs in clinical practice.The study found that with the increase of the dose,cisplatin will produce toxic side effects,of which the most serious is nephrotoxicity.At present,many domestic and foreign scholars have devoted themselves to the research how to reduce the nephrotoxicity of cisplatin,but so far there are few drugs that can be used clinically.Hydration therapy or osmotic diuretics are often used to reduce nephrotoxicity in clinical practice,but the incidence of nephrotoxicity caused by cisplatin is still as high as 30% or more.Therefore,search for a drug that can effectively inhibit the cumulative renal toxicity of cisplatin is still the current research hotspot.The saponins from leaves of P.quinquefolius(PQS)is considered to be the main component of American ginseng leaves.Recent studies have shown that PQS have a variety of pharmacological activities that can be used clinically,including reducing oxidative stress damage,anti-inflammatory,and scavenging free radicals.In this paper,we established the pharmacological model of cisplatin-induced acute renal toxicity in mice to observe the renal protective activity of PQS.Experimental data shows: The levels of blood urea nitrogen(BUN),serum creatinine(CRE),malondialdehyde(MDA),tumor necrosis factor-?(TNF-?)and interleukin-1?(IL-1?)were evidently increased in cisplatin-intoxicated mice,which were reversed by PQS.The activities of glutathione(GSH)and superoxide dismutase(SOD)in renal tissues were elevated.At the same time,overexpression of cytochrome P450 E1(CYP2E1)and heme oxygenase-1(HO-1)was reduced,suggesting that oxidative stress injury was improved.The results of Western blot showed that PQS pre-treatment significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4(Nox4),cleaved caspase-3,cleaved caspase-9,Bax,nuclear factor-?B(NF-?B),cyclooxygenase-2(COX-2),and inducible nitric oxide synthase(iNOS),suggesting the inhibition of apoptosis and inflammation response.H&E,PAS,Hoechst 33258 and TUNEL staining results showed that PQS can effectively improve the changes of renal cell structure and significantly reduce the apoptosis of renal cells induced by cisplatin,suggesting that it inhibited the apoptosis and inflammatory response of mice.The American ginseng berry extract(AGBE)is similar to the American ginseng berry,and its main active ingredient is ginsenoside.It exhibits various pharmacological activities such as anti-oxidation and anti-hyperglycemia in clinical treatment.Although many pharmacological effects of AGBE have been discovered,the protective activity against cisplatin-induced nephrotoxicity has not been reported so far.In this section,the renal protective activity of AGBE was observed by establishing a cisplatin-induced acute kidney injury model.The experimental results show that: AGBE can effectively reduce the mouse kidney index and the levels of CRE,BUN,MDA,TNF-? and IL-1?.Moreover,AGBE can improve the body weight of mice after one-time injection of cisplatin,and increased the content of GSH and SOD in renal tissue.The protein levels of CYP2E1,4-hydroxynonenal(4-HNE),COX-2,iNOS,Bax,protein expression of activated caspase-3 and cytochrome c was decreased,while the level of the anti-apoptotic protein Bcl-2 was increased.At the same time,AGBE significantly inhibited the activation of cisplatin-induced NF-?B and mitogen-activated protein kinase(MAPK)signaling pathways.H&E staining results showed that AGBE could significantly improve the histopathological changes.Hoechst 33258 and TUNEL staining confirmed that AGBE can effectively inhibit renal cell apoptosis.In conclusion,PQS and AGBE may exert renal protective activity against cisplatin-induced oxidative stress,inflammation,and apoptosis,and its possible molecular mechanism is to inhibit the activation of caspase-3/caspase-9,MAPK and NF-?B. |
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