The nephrotoxicity for mice of deisopropylngaione, a minor furanoid component of toxic myoporaceous essential oils.

Deisopropylngaione (DIN) is one of a family of hepatotoxic furanosesquiterpenoid essential oils which is found in small amounts (5%) in the leaves of some specimens of the Australian plant Myoporum deserti. DIN differs from other furanoid myoporaceous essential oils in that it also causes lesions in the lungs and kidneys. At the near LD50 dose rate of 150 mg kg-1 given by intraperitoneal injection, DIN is able to cause lethal renal proximal tubular necrosis without causing significant injury to the liver and lungs in adult male mice. Following dosing, there is an increase in kidney weight due mainly to increase in water content which reaches a maximum within 16-24 h. This is accompanied by degeneration and necrosis of the proximal tubular epithelium, with proteinuria and glucosuria lasting up to 9 days in non-lethally affected mice. Marked body weight loss due to the intoxication causes a marked increase in the kidney weight:body weight ratio lasting between 9 and 18 days. Residual lesions are still present in the kidneys at 32 days, but recovery is eventually complete. DIN is structurally similar to the sweet potato toxic furan 4-ipomeanol and, like the latter, is probably injurious to the kidneys through toxic metabolism by the cytochrome-P450-containing monooxygenases of the proximal tubular epithelium. Although slight renal injury is occasionally observed in livestock poisoned by myoporaceous plants, it is unlikely that DIN is the cause. So far, DIN, like 4-ipomeanol, appears to be unequivocally nephrotoxic only for the male mouse.