Publications (2)1.91 Total impact
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Article: Cisplatin-induced cytotoxicity in BSO-exposed renal proximal tubular epithelial cells: sex, age, and species.
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ABSTRACT: Cisplatin (CP)-induced kidney damage and effects of DL-buthionine-(S,R)-sulfoximine (BSO) on it are species- and age-different. It remains unclear whether CP-induced cytotoxicity in renal proximal tubular epithelial cells (RTEC), the main target cells of CP, is also species- and age-different; and whether CP-induced cytotoxicity varies with the difference in age and species, if any, is one of the questions. In the present study, the effects of BSO on CP-induced cytotoxicity in primary cultures of RTEC isolated from monkeys and different age and sex rats were studied. The RTEC were isolated from 3-week-old, 2-month-old, or 5-month-old rats, and 6-8 year-old monkeys. After subculturing, RTEC was inoculated into type I collagen-coated 96-well culture plates; after preincubation, 40 microM BSO was added, 16 hours later, varying concentrations of CP were added. At that time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were performed to test cell viability. The concentrations of CP that inhibited 50% cell growth (IC50) of RTEC from rats and monkeys were 1.11 and 3.03 mM at 8 hours, and 0.51 and 1.24 mM at 24 hours, respectively. The BSO made the IC50s of RTEC from rats and monkeys lower, down to 0.07 and 0.48 mM at 8 hours, and 0.02 and 0.11 mM at 24 hours, respectively. The IC50s of RTEC from different sex and age rats were almost same. These results suggested that CP-induced cytotoxicity was concentration- and time-dependent, with species-dependent differences, rat RTEC were more susceptible to CP than monkey RTEC, rat RTEC were more dependent on glutathione (GSH) during the stress state were than monkey cells; CP-induced cytotoxicity was without sex- and age-dependent differences in rat RTEC.Renal Failure 02/2005; 27(5):629-33. · 0.82 Impact Factor -
Article: Effects of BSO and L-cysteine on drug-induced cytotoxicity in primary cell cultures: drug-, cell type-, and species-specific difference.
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ABSTRACT: The effects of DL-buthionine-(S,R)-sulfoximine(BSO) and L-cysteine(CYS) on cytotoxicity induced by cisplatin(CP) and diclofenac(DIC) in primary cell cultures of hepatocytes and renal tubular epithelial cells(RTEC) isolated from rats or monkeys were studied. Hepatocytes and RTEC were inoculated into collagen-coated 96-well culture plates. After preincubation, a series of concentrations of CP or DIC were added, and 16 h and 4 h prior to CP and DIC, 40 microM BSO and 5 mM CYS were added, respectively. MTT assays were performed to evaluate cytotoxicity(concentrations of drug that inhibited 50% cell growth, IC50). CYS made IC50s of CP in rat and monkey RTEC increase up to more than 5 mM, but BSO made IC50s of CP in rat RTEC lower down with bigger magnitude than that in monkey RTEC; similarly, CYS made IC50s of CP in rat hepatocytes increase up to more than 5 mM, but BSO made IC50s lower down with bigger magnitude than that in rat RTEC. However, neither CYS nor BSO had significant effects on all IC50s of DIC in all examined cells. These results suggested that during CP-induced stress state, rat hepatocytes were more susceptible to changes of GSH level than rat RTEC, and rat RTEC were more dependent on intracellular GSH status than monkey RTEC. DIC-induced cytotoxicity in RTEC and hepatocytes is independent of GSH level.Drug and Chemical Toxicology 09/2004; 27(3):269-80. · 1.08 Impact Factor
