Abstract
Nephrotoxicity is a serious adverse effect of cisplatin chemotherapy that limits its clinical application, to deal with which no effective management is available so far. The present study was to investigate the potential protective effect of QiShenYiQi Pills (QSYQ), a compound Chinese medicine, against cisplatin induced nephrotoxicity in mice. Pretreatment with QSYQ significantly attenuated the cisplatin induced increase in plasma urea and creatinine, along with the histological damage, such as tubular necrosis, protein cast, and desquamation of epithelial cells, improved the renal microcirculation disturbance as indicated by renal blood flow, microvascular flow velocity, and the number of adherent leukocytes. Additionally, QSYQ prevented mitochondrial dysfunction by preventing the cisplatin induced downregulation of mitochondrial complex activity and the expression of NDUFA10, ATP5D, and Sirt3. Meanwhile, the cisplatin-increased renal thiobarbituric acid-reactive substances, caspase9, cleaved-caspase9, and cleaved-caspase3 were all diminished by QSYQ pretreatment. In summary, the pretreatment with QSYQ remarkably ameliorated the cisplatin induced nephrotoxicity in mice, possibly via the regulation of mitochondrial function, oxidative stress, and apoptosis.
Highlights
Cis-diamminedichloroplatinum is a highly effective chemotherapeutic drug against a wide range of cancers including testicular, ovarian, bladder, head and neck, uterine cervical carcinoma, non-small cell lung carcinoma, etc. (Dilruba and Kalayda, 2016)
The experimental procedures were in accordance with the Abbreviations: AKI, acute kidney injury; ANOVA, analysis of variance; ATP, adenosine triphosphate; ATP5D, ATP synthase δ-subunit; Bax, B-cell lymphoma-2 associated X protein; Bcl-2, B-cell lymphoma-2; BSA, bovine serum albumin; BUN, blood urea nitrogen; CTR, control; DDP, cis-diamminedichloroplatinum; DNA, deoxyribonucleic acid; ELISA, enzyme linked immunosorbent assay; NDUFA10, NADH:ubiquinone oxidoreductase subunit A10; periodic acid-Schiff (PAS), periodic acid schiff; PFA, paraformaldehyde; QSYQ, QiShenYiQi Pills; RBC, red blood cell; Renal blood flow (RBF), renal blood flow; ROS, reactive oxygen species; SDHA, succinate dehydrogenase complex flavoprotein subunit A; thiobarbituric acidreactive substances (TBARS), thiobarbituric acid reactive substances; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
All the manifestations were significantly protected by QSYQ pretreatment
Summary
Cis-diamminedichloroplatinum (cisplatin; DDP) is a highly effective chemotherapeutic drug against a wide range of cancers including testicular, ovarian, bladder, head and neck, uterine cervical carcinoma, non-small cell lung carcinoma, etc. (Dilruba and Kalayda, 2016). Cis-diamminedichloroplatinum (cisplatin; DDP) is a highly effective chemotherapeutic drug against a wide range of cancers including testicular, ovarian, bladder, head and neck, uterine cervical carcinoma, non-small cell lung carcinoma, etc. Nephrotoxicity is a frequent adverse effect which occurs in up to one-third of patients undergoing DDP therapy in spite of the intensive prophylactic measures used, such as aggressive hydration and forced diuresis. The antineoplastic effect of DDP has been principally ascribed to its ability to form intra- and interstrand DNA crosslinks that interfere with DNA replication and synthesis, and lead to cell death (Marullo et al, 2013). The mechanisms underlying DDP-induced nephrotoxicity are not fully understood. The discovery of new, effective treatments against DDP-induced nephrotoxicity is in need in order to increase the clinical utility of this drug
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