Thea sinensis melanin prevents cisplatin-induced nephrotoxicity in mice.
The preventive effect of Thea sinensis melanin (TSM) against cisplatin-induced nephrotoxicity was studied on ICR mice. Animals were given 20mg/kg i.p. of cisplatin, and TSM was injected i.p. in doses 10-40 mg/kg 2h before intoxication. The protective effects were evidenced by a complete inhibition of the cisplatin-induced elevation of serum Blood Urea nitrogen (BUN), prevention of oxidative stress, and complete blockade of cisplatin-induced elevation of serum creatinine. TSM by itself, however, did not affect the renal functional parameters, including serum BUN and creatinine. Real-time RT-PCR was applied to quantify mRNA levels of cisplatin-treated mouse kidney compared to normal mouse kidney for selected marker genes. Cisplatin treatment increases mRNA levels 40-fold for glutathione-S-transferases (Gstp2), 15-fold for soluble epoxide hydrolase (Ephx1), 15-fold for lipocalin 2 (Lcn2), 9-fold for lysozyme (Lyz), 5-fold for UDP glycosyltransferase 2 (Utg2b), 30-fold for survival motor neuron (Smn1), 30-fold for guanidinoacetate methyltransferase (Gamt), 80-fold for urine retinol binding protein (Rbp4), 60-fold for aminopeptidase N (Apn), 60-fold for cytochrome P450 (Cyp2d18), and 100-fold for ornithine aminotransferase (Oat). Pre-administration of TSM restored normal expression of marker genes for cisplatin-treated mouse kidneys. TSM by itself, however, did not affect the transcription for marker genes. Results obtained demonstrate that TSM pre-administration can prevent the renal toxic effects of cisplatin.
Hung
Yao-Ching
YC
Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, China Medical University, 91 Hsueh Shih Road, Taichung 404, Taiwan.
Huang
G Steven
GS
Lin
Li-Wei
LW
Hong
Meng-Yen
MY
Se
Pei-San
PS
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D028241:Camellia sinensis / Q000737:chemistry*; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005819:Genetic Markers / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008543:Melanins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; D004798:Enzymes; D005819:Genetic Markers; D008543:Melanins; D010936:Plant Extracts; D012333:RNA, Messenger; D002945:Cisplatin