Why is grape toxic to mice? - briefly
Grapes contain an unidentified nephrotoxin that causes acute kidney injury and rapid death in mice. The toxin induces renal tubular necrosis and disrupts electrolyte balance.
Why is grape toxic to mice? - in detail
Grapes cause acute kidney injury in mice after oral ingestion. Laboratory studies show that even small amounts (approximately 0.5 g per kilogram of body weight) can trigger rapid loss of renal function, manifested by elevated blood urea nitrogen and creatinine levels within hours. Histological examination reveals tubular necrosis, interstitial inflammation, and obstruction of renal lumina.
The toxic agent has not been isolated, but several candidates are under investigation. Tartaric acid, present in high concentrations in grape skins and seeds, induces oxidative stress and mitochondrial dysfunction in renal epithelial cells. Phenolic compounds such as resveratrol and quercetin, while antioxidant in low doses, become pro‑oxidant at higher concentrations, generating reactive oxygen species that damage cellular membranes. Additionally, unidentified water‑soluble substances appear to interfere with the sodium‑potassium ATPase pump, disrupting electrolyte balance and precipitating cellular edema.
Mechanistic studies suggest a two‑phase response. The first phase involves direct cytotoxicity to proximal tubule cells, leading to loss of brush‑border integrity and leakage of intracellular enzymes. The second phase triggers a systemic inflammatory cascade, with up‑regulation of cytokines (TNF‑α, IL‑6) that exacerbate renal damage and contribute to multi‑organ failure. In vitro assays demonstrate that mouse kidney cell lines exposed to grape extracts exhibit dose‑dependent decreases in viability, confirming the relevance of the observed in vivo effects.
Comparative research indicates that susceptibility varies among rodent strains. Inbred C57BL/6 mice display higher mortality rates than outbred CD‑1 mice, likely due to genetic differences in detoxification pathways, particularly cytochrome P450 isoforms and glutathione‑S‑transferase activity. This variability underscores the importance of strain selection when modeling grape‑induced nephrotoxicity.
Experimental protocols recommend fasting mice for 4–6 hours before administration to standardize absorption, using freshly prepared grape homogenate to avoid degradation of active constituents. Post‑exposure monitoring includes serial blood sampling for renal biomarkers, urine output measurement, and non‑invasive imaging (ultrasound) to assess kidney size and perfusion.
Current evidence does not identify a single molecule responsible for the harmful effects; instead, a synergistic interaction among multiple grape components appears to drive renal injury. Further purification and mass‑spectrometry analyses are required to pinpoint the primary toxic factor, which could inform risk assessments for other species, including humans.