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1325. Sporidesmin and lipid metabolism
NATURAL PRODUCTS
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NATURAL PRODUCTS 1324. Yet more ftmgal hepatotoxias Townsend, R. J., Moss, M. O. & Peck, H. Monica (1966). Isolation and characterisation of hepatotoxins from Penicillium rubrum. J. Pharm. Pharmac. 18, 471." An alarming number of toxigenic fungi, a high proportion of which are hepatotoxic, has now been isolated from mouldy foodstuffs. Diets contaminated with Penicillium rubrum have already been shown to be highly toxic to ducklings, but much less toxic to mice and rats (Cited in F.C.T. 1966, 4, 242). The hepatotoxic potential of a crude toxin obtained from this fungus has now been demonstrated. The acute oral and intraperitoneal toxicities of crude toxin, isolated from a culture of P. rubrum, were found to be 120 and 3.75 mg/kg, respectively, in mice and of the same order of toxicity in ducklings. Post-mortem examination of acutely poisoned mice revealed mottled livers with extensive haemorrhages, slightly anaemic kidneys and occasional haemorrhages in the lungs. But no macroscopic liver lesions were observed 7 days after administration of sublethal doses of the toxin to mice, rats, ducklings or guinea-pigs. In spite of this, liver metabolism was adversely affected, as shown by the marked prolongation ofphenobarbitone sleeping time in mice, indicating interference with the normal detoxicating mechanism. Two toxins, rubratoxins A and B, with similar infrared spectra, were isolated from the crude material. Rubratoxin A, with an acute intraperitoneal toxicity in mice slightly higher than that of the crude toxin, has been crystallized and partially characterized. [Toxicologists will hope that they are not kept too long in suspense before the analytical chemists have cracked this nut.]
1325. Sporidesmin and lipid metabolism Peters, J. A. (1966). Effect of sporidesmin on lipid metabolism in rabbits. Nature, Lond. 210, 601. An accumulation of triglyceride (TG) in the liver is one of the earliest biochemical manifestations induced in sheep and rabbits by the fungal toxin, sporidesmin (I) (Mortimer & Taylor, Nature, Lond. 1962, 194, 550). Within 24 hr of administration of an oral dose of 1 mg I/kg, the liver TG level was elevated, but the increase was not so marked at 48 hr, a pattern which resembles the action of other hepatotoxins. Serum TG was also raised at 24 hr indicating that I not only inhibits the hepatic release of TG but also affects its uptake from the circulation by adipose tissue. That hepatic accumulation of TG was not due to increased mobilization of free fatty acids (FFA) from adipose tissue was shown by a fall in serum FFA. The fatty livers induced by other hepatotoxins are caused by inhibited synthesis of the protein moiety of lipoproteins (Cited in F.C.T. 1966, 4, 79), the form in which TG is released from the liver into the circulation. Since the protein content of liver mitochondria is reduced 24 hr after administration of I (ibid 1965, 3, 355), it is suggested that transitory inhibition of protein synthesis accounts for the increase in liver TG induced by I. After 48 hr, rises in serum phospholipids, cholesterol and cholesterol esters also became apparent and were accompanied by haemolysis and elevated serum bile acids and bilirubin. The same changes have been observed in sheep poisoned with I. The gradual accumulation of bile acids in the liver and circulation is considered to be related to the pathological and chemical changes that occur as the disease progresses.
1326. Fungal contamination of foods and porphyria Keen, G. A., Saunders, S. J. & Eales, L. (1966). Porphyrin production in liver cells by Aspergillus fumigatus. Lancet i, 798.
439
NATURAL PRODUCTS 1324. Yet more ftmgal hepatotoxias Townsend, R. J., Moss, M. O. & Peck, H. Monica (1966). Isolation and characterisation of hepatotoxins from Penicillium rubrum. J. Pharm. Pharmac. 18, 471." An alarming number of toxigenic fungi, a high proportion of which are hepatotoxic, has now been isolated from mouldy foodstuffs. Diets contaminated with Penicillium rubrum have already been shown to be highly toxic to ducklings, but much less toxic to mice and rats (Cited in F.C.T. 1966, 4, 242). The hepatotoxic potential of a crude toxin obtained from this fungus has now been demonstrated. The acute oral and intraperitoneal toxicities of crude toxin, isolated from a culture of P. rubrum, were found to be 120 and 3.75 mg/kg, respectively, in mice and of the same order of toxicity in ducklings. Post-mortem examination of acutely poisoned mice revealed mottled livers with extensive haemorrhages, slightly anaemic kidneys and occasional haemorrhages in the lungs. But no macroscopic liver lesions were observed 7 days after administration of sublethal doses of the toxin to mice, rats, ducklings or guinea-pigs. In spite of this, liver metabolism was adversely affected, as shown by the marked prolongation ofphenobarbitone sleeping time in mice, indicating interference with the normal detoxicating mechanism. Two toxins, rubratoxins A and B, with similar infrared spectra, were isolated from the crude material. Rubratoxin A, with an acute intraperitoneal toxicity in mice slightly higher than that of the crude toxin, has been crystallized and partially characterized. [Toxicologists will hope that they are not kept too long in suspense before the analytical chemists have cracked this nut.]
1325. Sporidesmin and lipid metabolism Peters, J. A. (1966). Effect of sporidesmin on lipid metabolism in rabbits. Nature, Lond. 210, 601. An accumulation of triglyceride (TG) in the liver is one of the earliest biochemical manifestations induced in sheep and rabbits by the fungal toxin, sporidesmin (I) (Mortimer & Taylor, Nature, Lond. 1962, 194, 550). Within 24 hr of administration of an oral dose of 1 mg I/kg, the liver TG level was elevated, but the increase was not so marked at 48 hr, a pattern which resembles the action of other hepatotoxins. Serum TG was also raised at 24 hr indicating that I not only inhibits the hepatic release of TG but also affects its uptake from the circulation by adipose tissue. That hepatic accumulation of TG was not due to increased mobilization of free fatty acids (FFA) from adipose tissue was shown by a fall in serum FFA. The fatty livers induced by other hepatotoxins are caused by inhibited synthesis of the protein moiety of lipoproteins (Cited in F.C.T. 1966, 4, 79), the form in which TG is released from the liver into the circulation. Since the protein content of liver mitochondria is reduced 24 hr after administration of I (ibid 1965, 3, 355), it is suggested that transitory inhibition of protein synthesis accounts for the increase in liver TG induced by I. After 48 hr, rises in serum phospholipids, cholesterol and cholesterol esters also became apparent and were accompanied by haemolysis and elevated serum bile acids and bilirubin. The same changes have been observed in sheep poisoned with I. The gradual accumulation of bile acids in the liver and circulation is considered to be related to the pathological and chemical changes that occur as the disease progresses.
1326. Fungal contamination of foods and porphyria Keen, G. A., Saunders, S. J. & Eales, L. (1966). Porphyrin production in liver cells by Aspergillus fumigatus. Lancet i, 798.