Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium

Abstract

It is well known that when lactating livestock eat avocado (Persea americana) leaves they may develop non-infectious mastitis and agalactia. This is associated with extensive coagulation necrosis of the secretory acinar epithelium and interstitial oedema, congestion, and haemorrhage. Similar lesions have been produced in mammary glands of lactating mice fed a diet containing a small percentage of freeze-dried avocado leaf. Tests using these animals have been used to isolate the active principle, termed "persin," from avocado leaves. The purified persin was examined using IR, NMR, and UV spectroscopy and mass spectrometry, and identified as (Z,Z)-1-(acetyloxy)-2-hydroxy-12,15-heneicosadien-4-one. Persin has previously been isolated from avocado leaves and shown to have antifungal properties and to be toxic to silkworms. Our tests have shown that persin at the dose rate of 60-100 mg/kg has the same effect on mammary glands in lactating mice as leaves from avocado. Enantioselective syntheses of the R and the S isomers of persin and related derivatives were carried out. These compounds were tested for activity required to induce widespread lactating mammary gland necrosis in mice, and only the R isomer was found active. At doses of persin above 100 mg/kg necrosis of myocardial fibres may occur and hydrothorax may be present in severely affected animals. The mechanism of action of persin on both the mammary gland and the myocardium remain to be resolved.

Review of substances/agents that have direct beneficial effect on the environment: mode of action and assessment of efficacy

“…This extract is associated with congestive heart failure related to severe cardiomyopathy in goats, horses and sheep. The plant leaves are reported to have caused severe cardivascular and lung damage and death in goats Oelrichs et al, 1995;.…”

The Cytotoxic Effects of Novel Persin Analogues on a Breast Cancer Cell Line

“…The epithelium did not appear to regenerate, and more severely damaged tissue was replaced by scar and adipose tissue (Oelrichs et al, 1995). These results, correlating with the effects of ingestion of avocado leaves, suggest that persin is likely the most notable toxin in avocado leaves (Oelrichs et al, 1995).…”

“…This observation led to the isolation of persin, an unsaturated fatty acid, closely related in structure to the essential fatty acid linoleic acid and exhibiting necrotic activity in the R configuration (Oelrichs et al, 1995). One study found that treatment with 60-100 mg/kg of persin has the same effect on lactating mice as ingestion of avocado leaves: interstitial edema, congestion, hemorrhage, and coagulative necrosis and shedding of the mammary gland epithelium (Oelrichs et al, 1995). The epithelium did not appear to regenerate, and more severely damaged tissue was replaced by scar and adipose tissue (Oelrichs et al, 1995).…”

“…One study found that treatment with 60-100 mg/kg of persin has the same effect on lactating mice as ingestion of avocado leaves: interstitial edema, congestion, hemorrhage, and coagulative necrosis and shedding of the mammary gland epithelium (Oelrichs et al, 1995). The epithelium did not appear to regenerate, and more severely damaged tissue was replaced by scar and adipose tissue (Oelrichs et al, 1995). These results, correlating with the effects of ingestion of avocado leaves, suggest that persin is likely the most notable toxin in avocado leaves (Oelrichs et al, 1995).…”

“…Although the previously discussed studies suggest that persin or its derivatives may have significant potential as a chemotherapeutic drug, it was noted that persin treatment in mice damages not only lactating mammary glands, but also results in necrosis of myocardial fibers of the heart and potential hydrothorax and pulmonary edema (Oelrichs et al, 1995). These results prompt the search for other compounds that may be specific only to breast cancer cells.…”