Amelioration of cisplatin toxicity by a fermented grain food product.
The most noticeable hypothesis regarding the pathogenesis of cisplatin toxicity, seen mainly in kidney and intestine, is oxidative stress, an imbalance between free-radical generating cisplatin and radical scavenging systems. This paper describes the role of the antioxidant system in cisplatin-induced toxicity and the protective effect by a processed grain food (Antioxidant Biofactor: AOB), which has been shown to exhibit strong antioxidant activity. Male Fischer 344 rats were used. They were pre-fed either a basal diet (control, 15 g/day) or the diet supplemented with AOB to provide 6.5% or 20% of total diet throughout the experiment. Cisplatin (5 mg/kg, i.v.) was administered at the start of the experiment, and the animals were sacrificed 5 days later. Blood urea nitrogen (BUN) and plasma creatinine, NO2(-) and NO3(-) (NOx) were determined from the plasma. The levels of 4-hydroxy-2-nonenal (a lipid peroxidation product), 8-hydroxy-deoxyguanosine (8-OHdG, an oxidatively modified DNA adduct) and nitrotyrosine were histologically analyzed. The cisplatin administration resulted in a loss of body weight and elevations of BUN, serum creatinine and NOx levels, whereas AOB supplement reversed these effects. The severe morphological damages induced in the kidney and intestine by the cisplatin administration were markedly improved in the AOB group. The levels of lipid peroxidation, 8-OHdG, and nitrotyrosine all paralleled the morphological damage. The AOB effect was dose dependent. In conclusion, the present study suggests that certain food additives like AOB may be of benefit against the side effects of cisplatin.
Minamiyama
Yukiko
Y
Department of Food and Health Science, Graduate School of Medicine and Dentistry, Okayama University, Shikatacho, Okayama 700-8558, Japan. yukiko@med.osaka-cu.ac.jp
Takemura
Shigekazu
S
Toyokuni
Shinya
S
Nishino
Yoshihiro
Y
Yamasaki
Keiichi
K
Hai
Seikan
S
Yamamoto
Satoshi
S
Okada
Shigeru
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000032:analysis; D000818:Animals; D000975:Antioxidants; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004032:Diet; D002523:Edible Grain; D005285:Fermentation; D007422:Intestines / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D015431:Weight Loss / Q000187:drug effects
D000447:Aldehydes; D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D002945:Cisplatin