Experimentation of using Cisplatin produced by Vietnam with dose of LD50=26.00 (23.21-29.12) mg/kg on injection line on peritoneum of white house-mice was monitored for a week, and the 100% mice died. Before the death, the mice often had some kinds of epilepsy. It was proved that this medicine affected on central nervous system. In terms of semi-chronic toxicity, Cisplatin with dose of 0.2mg/kg/24 hours of intravenous injections 5 days per course, with dose of 0.3mg/kg/24 hours of intravenous injection in 5 days, using two courses after 10 days changed some indexes of hematology and microscopic findings of bone marrow. After 15 days to 30 days of discontinuous injection, injuries gradually recovered
Cisplatin ; Cisplatin/toxicity

Cisplatin was intravenously injected at the dose of 0.2 mg/kg (equivalent to 1/10 of the maximum non-toxicating dose in mice) four 5-day episodes with the interval of 5 days caused a slight increase in the serum creatinine and urea levels. Similar effects were also observed when cisplatin was IV administered at 0.3 mg/kg/24h for two 5-day episodes with the interval of 10 days. Other mild side effects towards liver and some organs were also observed in about 50% of the mice population. Most of the side effects significantly subdued in both groups 15 days after stopping drug, except damages in hepatic histology, which recovered more slowly
Cisplatin ; Cisplatin/toxicity ; Liver ; Kidney

OBJECTIVE: Chemotherapeutic drugs, such as cisplatin (CP), which are associated with oxidative stress and apoptosis, may adversely affect the reproductive system. This study tests whether administration of propolis and nano-propolis (NP) can alleviate oxidative stress and apoptosis in rats with testicular damage induced by CP. METHODS: In this study, polymeric nanoparticles including propolis were synthesized with a green sonication method and characterized using Fourier transform-infrared spectroscopy, Brunauer-Emmett-Teller, and wet scanning transmission electron microscopy techniques. In total, 56 rats were divided into the following seven groups: control, CP, propolis, NP-10, CP + propolis, CP + NP-10, and CP + NP-30. Propolis (100 mg/kg), NP-10 (10 mg/kg), and NP-30 (30 mg/kg) treatments were administered by gavage daily for 21 d, and CP (3 mg/kg) was administered intraperitoneally in a single dose. After the experiment, oxidative stress parameters, namely, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), and apoptotic pathways including B cell leukemia/lymphoma-2 protein (Bcl-2) and Bcl-2-associated X protein (Bax) were measured in testicular tissues. Furthermore, sperm quality and weights of the testis, epididymis, right cauda epididymis, seminal vesicles and prostate were evaluated. RESULTS: Propolis and NP (especially NP-30) were able to preserve oxidative balance (decreased MDA levels and increased GSH, CAT, and GPx activities) and activate apoptotic pathways (decreased Bax and increased Bcl-2) in the testes of CP-treated rats. Sperm motility in the control, CP, and CP + NP-30 groups were 60%, 48.75%, and 78%, respectively (P < 0.001). Especially, NP-30 application completely corrected the deterioration in sperm features induced by CP. CONCLUSION The results show that propolis and NP treatments mitigated the side effects of CP on spermatogenic activity, antioxidant situation, and apoptosis in rats.
Animals ; Antioxidants/metabolism* ; Cisplatin/toxicity* ; Male ; Oxidative Stress ; Propolis ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; Testis

BACKGROUND/AIMS: Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. METHODS: Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-alpha, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy. RESULTS: Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-alpha, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells. CONCLUSIONS: DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effects.
Animals ; Anti-Inflammatory Agents/pharmacology ; Antineoplastic Agents/*toxicity ; Apoptosis/drug effects ; Cisplatin/*toxicity ; Erythropoietin/*analogs & derivatives/pharmacology ; Hematocrit ; Kidney/*drug effects/pathology ; Male ; Rats ; Rats, Sprague-Dawley

Animals ; Antineoplastic Agents ; toxicity ; Cisplatin ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; Hearing Loss ; chemically induced ; Male ; Mice ; Mice, Inbred Strains ; Salvia miltiorrhiza

Animals ; Antineoplastic Agents ; toxicity ; Brain ; metabolism ; Cisplatin ; toxicity ; DNA Damage ; drug effects ; Deoxyguanosine ; analogs & derivatives ; analysis ; Female ; Kidney ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; drug effects

OBJECTIVE: To study the effect of forsythiaside on the expression of c-jun induced by cisplatin in the cochlea of guinea pig. METHOD: Thirty guinea pigs were randomly divided into control group (10), cisplatin group (10) and forsythiaside group (10). The ototoxicity model was done with intraperitoneal injection of cisplatin solution (8 mg/kg per day) for 7 days. Forsythiaside (25 mg/kg per day) was injected 30 min before cisplatin solution treated in guinea pigs of forsythiaside group for 7 consecutive days. The saline instead of cisplatin was injected in normal control group. The distortion product otoacoustic emission (DPOAE) was detected before animals were killed. The expression of c-jun in cochlea of guinea pigs was detected by western blotting. The expression of c-jun mRNA in cochlea of guinea pigs was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: DPOAE amplitudes in cisplatin group was significantly lower than in control group (P < 0.01). Compared with cisplatin group, DPOAE amplitudes in forsythiaside group was increased significantly (P < 0.05). The expression of c-jun protein and mRNA were significantly increased in cisplatin group than in control group (P < 0.01). Compared with cisplatin group, the expression of c-jun protein and mRNA were significantly decreased in forsythiaside group. CONCLUSION Forsythiaside can significantly reduce the side effects induced by cisplatin through down-regulating the expression of c-jun.
Animals ; Cisplatin ; toxicity ; Cochlea ; drug effects ; metabolism ; Female ; Glycosides ; pharmacology ; Guinea Pigs ; Male ; Proto-Oncogene Proteins c-jun ; metabolism

BACKGROUND/AIMS: We retrospectively analyzed comparative toxicities and efficacies of chemotherapy regimens in advanced gastric cancer (AGC) patients who achieved complete response (CR) after chemotherapy. METHODS: We reviewed the medical records of 1,203 patients, who were pathologically diagnosed as AGC in a single center between January 2001 and October 2007. On the basis of the Response Evaluation Criteria in Solid Tumors, CR was evaluated with abdominal computed tomography. Toxicities were evaluated using the National Cancer Institute's common toxicity criteria before each chemotherapy cycle. RESULTS: Among the 1,203 AGC patients enrolled in this study, 568 received chemotherapy and 635 received best supportive care. The major chemotherapy regimens were 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), docetaxel, cisplatin and 5-fluorouracil (DCF) and 5-fluorouracil, leucovorin and irinotecan (FOLFIRI). Among the 568 patients, 51 (9.0%) achieved CR (49 [8.6%] with FOLFOX [n=12], DCF [n=26], or FOLFIRI [n=11] and 2 [0.3%] with etoposide, leucovorin and 5-fluorouracil). For patients administered FOLFOX, DCF, and FOLFIRI, the median time to disease progression was 4 months (range, 1.8-59.5), 15 months (range, 2.9-31.2) and 10 months (range, 2.0-39.5), and the median survival times were 48 months (range, 5.9-74.0), 37 months (range, 14.0-86.0), and 30 months (range, 6.0-50.0), respectively. Grades 3-4 mucositis occurred mostly in patients administered DCF (n=8, 30.8%). Grades 3-4 leucopenia were observed in 1 (8.3%), 11 (42.3%), and 4 (36.4%) patients administered FOLFOX, DCF and FOLFIRI, respectively. No statistically significant differences were observed in the 3 regimens. CONCLUSIONS: All 3 regimens (FOLFOX, DCF and FOLFIRI) were active and tolerable. Their efficacies and toxicities were not significantly different.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use/toxicity ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use/toxicity ; Camptothecin/analogs & derivatives/therapeutic use/toxicity ; Cisplatin/therapeutic use/toxicity ; Drug Therapy, Combination ; Female ; Fluorouracil/therapeutic use/toxicity ; Humans ; Leucovorin/therapeutic use/toxicity ; Leukopenia/etiology ; Male ; Middle Aged ; Mucositis/etiology ; Nausea/etiology ; Neoplasm Staging ; Organoplatinum Compounds/therapeutic use/toxicity ; Retrospective Studies ; Stomach Neoplasms/*drug therapy/mortality ; Survival Rate ; Taxoids/therapeutic use/toxicity ; Tomography, X-Ray Computed ; Vomiting/etiology

Biliverdin (BV) has long been thought to be a cytotoxic metabolic waste product. It has also been demonstrated to have important cytoprotective functions during oxidative stress. The present study aimed to examine the cytoprotective effect of BV on NRK-52E cells, a proximal tubular cell line derived from rat kidney. Cells were treated with 50 µmol/L cisplatin for 24 h (cisplatin group) or pre-treated with BV for 30 min, then with 50 µmol/L cisplatin for 24 h (cisplatin+BV group). Those given no treatment served as a control. Cell apoptosis was evaluated by flow cytometry and cell viability by Cell Counting Kit-8 (CCK-8). The protein expressions of cleaved caspase3, Bax and Bcl-2 were assessed by Western blotting. Reactive oxygen species (ROS) levels were measured using carboxydichlorodihydrofluorescein diacetate (H2DCF). The results showed that cisplatin induced the apoptosis of NRK-52E cells, decreased cell viability, and increased the formation of ROS by upregulating the expression of cleaved caspase3 and Bax and decreasing Bcl-2 protein expression. These effects could be significantly reversed by pretreatment with BV. It was concluded that BV can protect against cisplatin-induced cell apoptosis through the anti-oxidative effects.
Animals ; Antioxidants ; pharmacology ; Apoptosis ; Biliverdine ; pharmacology ; Cell Line ; Cisplatin ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; Kidney Tubules ; cytology ; Rats ; Reactive Oxygen Species ; metabolism

OBJECTIVETo study the protective effect of Ligustrazine Injection (LI) against cisplatin-induced ototoxicity and to explore its mechanism.

METHODSThirty healthy adult guinea pigs were randomly divided into three groups, 10 in each group, i.e., the normal control group, the cisplatin group, and the LI group. Guinea pigs in the normal control group were intraperitoneally injected with normal saline at 3 mL/kg for 7 consecutive days. Those in the cisplatin group were intraperitoneally injected with cisplatin at 3 mg/kg for 7 consecutive days. Those in the LI group were intraperitoneally injected with LI at 140 mg/kg for 7 days, but cisplatin (3 mg/kg) was intraperitoneally injected from the opposite side starting from the 4th day. Brainstem auditory evoked potential (BAEP) was performed in all animals before and after injection. All animals were sacrificed after the final testing under anesthesia and their cochleas collected. Half the cochleas of each group were collected for silver nitrate staining of cochlear basilar membrane stretched. The other half the cochleas of each group made into paraffin sections to observe the apoptosis of cochlea cells by TUNEL method and the expression levels of c-Jun detected by immunohistochemistry.

RESULTSThere was no statistical difference in the difference of BAEP threshold among the 3 groups before injection (P > 0.05), but the BAEP threshold increased in the cisplatin group and the LI group (P < 0.05). Besides, it was higher in the cisplatin group (P < 0.05). In the cisplatin group, most hair cells were missing, spiral ganglion cells obviously decreased, more TUNEL positive cells occurred, and the expression of c-Jun was stronger. But the aforesaid impairment in the LI group was obviously lessened (P < 0.05).

CONCLUSIONSLI showed certain antagonist effect on cisplatin-induced ototoxicity. Its mechanism might be associated with scavenging oxygen radicals of the cochlea tissue, improving the microcirculation, and fighting against apoptosis.

Animals ; Apoptosis ; drug effects ; Cisplatin ; toxicity ; Cochlea ; drug effects ; metabolism ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Pyrazines ; pharmacology ; Reactive Oxygen Species ; metabolism