This pharmacology study screened bismuth compounds for protection against kidney damage from the cancer drug cisplatin and identified bismuth tetraphenylporphyrinate as the most effective. Given orally to mice, it reduced kidney injury and let two thirds of mice survive a lethal cisplatin dose, caused no or negligible rise in a kidney injury marker when given alone, and was absorbed with a peak plasma bismuth of 16.8 µg/L before accumulating in the kidney.
Key numbers
- Synthesized bismuth compounds had half-cytotoxic concentrations above 100 µM in two mammalian cell types (p. 2).
- Single oral dose of 50 mg/kg bismuth tetraphenylporphyrinate in mice: peak plasma bismuth 16.8 µg/L at 1 hour, AUC0-48h 370.2 h·µg/L, estimated plasma half-life 6 hours; kidney bismuth accumulated over 48 hours (shown in a figure); three mice per time point (p. 3; Figure 2 legend, p. 4).
- Survival after a lethal cisplatin dose (20 mg/kg): 66.7% with bismuth tetraphenylporphyrinate versus no survivors with cisplatin alone within five days; eight mice per group (p. 3).
- Blood urea nitrogen rose from 17.7 to 171.1 mg/dL with cisplatin alone; the bismuth compounds given alone caused no or negligible increase (p. 2, Figure 2B).
- The authors state that plasma bismuth remained well under a documented safety level of 50 µg/L and an alarm level of 100 µg/L, citing earlier work (p. 11).
Methods (brief)
Bismuth(III) compounds were synthesized, screened in HK-2 human kidney cells against cisplatin, and the most active given orally to mice before and after an intraperitoneal lethal cisplatin dose. Endpoints included blood urea nitrogen, kidney platinum, body weight, survival, plasma and kidney bismuth over 48 hours, transcriptomics and tumor growth in a xenograft model. Full methods are in a supplemental file.
Evidence fitness
The study supports statements about oral absorption, plasma kinetics and kidney accumulation of one synthetic bismuth compound in mice, and about the absence of a kidney injury signal from that compound alone in a short experiment. It does not support statements about dietary bismuth, chronic toxicity, or safe human intakes. The plasma safety and alarm levels are cited from earlier literature, not derived here.
Limitations
Short-term mouse experiments with a synthetic compound designed for drug use. Kidney bismuth values are shown only in a figure. The compound degraded with light and moisture (p. 12). Funding came from Hong Kong public research funds and a university foundation.
Related evidence
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