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Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. 1997

O A Badary, and M N Nagi, and O A al-Shabanah, and H A al-Sawaf, and M O al-Sohaibani, and A M al-Bekairi
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi-Arabia.

The effects of thymoquinone (TQ) on cisplatin-induced nephrotoxicity in mice and rats were studied. Oral administration of TQ (50 mg/L in drinking water) for 5 days before and 5 days after single injections of cisplatin (5 mg/kg, i.v., in rats and 7 or 14 mg/kg, i.p., in mice) greatly ameliorated cisplatin-induced nephrotoxicity in both species. In rats, i.v. cisplatin caused 4- and 5-fold elevations in serum urea and creatinine, a 235% increase in urine volume, a 41% increase in kidney weight, 8.5-fold decrease in creatinine clearance, and extensive histological damage 5 days after treatment. In mice, similar alterations in kidney function were observed. TQ-induced amelioration of cisplatin nephrotoxicity was evident by significant reductions in serum urea and creatinine and significant improvement in polyuria, kidney weight, and creatinine clearance. The protective effects of TQ against cisplatin-induced nephrotoxicity in the rat were further confirmed by histopathological examination. To evaluate the possible modification of the antitumor activity of cisplatin by TQ, we studied their interaction in Ehrlich ascites carcinoma (EAC) bearing mice. The results revealed that TQ potentiated the antitumor activity of cisplatin. The current study suggests that TQ may improve the therapeutic index of cisplatin.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D016227 Benzoquinones Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. 1,2-Benzoquinones,1,4-Benzoquinones,Benzodiones,2,5-Cyclohexadiene-1,4-Diones,o-Benzoquinones,p-Benzoquinones
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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