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275. Ethylene glycol and renal calcium oxalate deposits
296
PROC'F~ING AND PACKAGING CONTAMINANTS
275. Ethylene glycol and renal calcium oxalate deposits In their previous paper (Tanret et al. C. R. Soc. Biol., Paris 1961, 155, 1025) the authors reported that ethylene giycol (I) led to the formation of calcium oxalate (II) deposits in the kidneys of male but not female rats. They now report a further study of this phenomenon. Groups of normal and castrated rats were all given 1% I in their drinking water for 27 days together with various other treatments: intact and castrated males and females received female sex hormone injections (oestradiol benzoate) and male sex hormone (testosterone propionate) respectively. After sacrifice the presence or absence of stones was noted and the relative kidney weights and the amounts of calcium/100 g fresh kidney were determined. In the intact and castrated males kidney stones were present and the kidney Ca contents were over 20 times as high as in the controls, but in the corresponding females no increases in Ca levels compared to those of the controls and no stones were observed. Female hormone when administered to both intact and castrated rats prevented stone formation and reduced kidney Ca levels to those of the control or female animals. No stones nor any effect on the Ca levels resulted from the injection of male hormone in intact females. Stones were however formed in castrated females and the Ca content of the kidney was raised to a level intermediate between those arising from the ingestion of I by intact males and females. The formation of kidney stones and exhibition of raised kidney Ca levels on continued ingestion of I was therefore normally confined to the male rat, under the conditions of these experiments. Rats treated with hormones of the opposite sex however tended to reflect the characteristics of the opposite rather than their own sex in relation to the effect on the kidney of I. Tanret, P., Thomas, J., Thomas, E. & Cottenot, F. (1962). Influence du sexe sur les formations de d~p6ts d'oxalate de calcium dans les reins chez le Rat intoxique par l'rthyl~ne-glycol. C.R. Soc. BioL, Paris 156, 1285.
276. Electron microscopic studies on diethylene glycol poisoning Electron microscopy has been employed to investigate the early effects in the rat of single doses of 15-25 ml diethyleneglycol (I)/kg on the proximal convoluted tubules of the kidney, and of 7.5-10 ml carbon tetrachloride (II)/kg on the cells of the liver. 30 min after I was administered, the mitochondria of the epithelial cells of the renal tubules were seen to be swollen. Breakdown of the internal lateral walls (cristae) of the mitochondria occurred and vacuoles appeared within these organelles after 3 hr. Up to this stage use of the light microscope failed to reveal these changes. At 12-24 hr larger vacuoles appeared in the cells due partly to the invagination of the basal parts of the cytoplasm and partly to an increase in size of the lumina of the rough-surfaced endoplasmic reticulum. A partial loss of the surface granules of the reticular membranes was also observed. Vacuole formation was also noted in the cells of the distal convoluted tubules at 24 hr. Swelling and vacuolation of the mitochondria, although less pronounced, was also the earliest change produced by II in the fiver cells. The most obvious change however occurred at 12 hr and consisted of the appearance of large vacuoles within the cell cytoplasm due to the enlargement of the space within the endoplasmic reticulum. [Our readers must forgive the technical terminology, which cannot readily be .explained in simple language. The crux of the matter is that, by using the electron microscope, one can detect morphological changes much earlier after the onset of toxic action. These changes might well be missed by other present-day methods. Nevertheless the huge doses used by the author are indicative of the sledge-hammer approach which we decry. It is obvious that more subtle tests are called for.]
PROC'F~ING AND PACKAGING CONTAMINANTS
275. Ethylene glycol and renal calcium oxalate deposits In their previous paper (Tanret et al. C. R. Soc. Biol., Paris 1961, 155, 1025) the authors reported that ethylene giycol (I) led to the formation of calcium oxalate (II) deposits in the kidneys of male but not female rats. They now report a further study of this phenomenon. Groups of normal and castrated rats were all given 1% I in their drinking water for 27 days together with various other treatments: intact and castrated males and females received female sex hormone injections (oestradiol benzoate) and male sex hormone (testosterone propionate) respectively. After sacrifice the presence or absence of stones was noted and the relative kidney weights and the amounts of calcium/100 g fresh kidney were determined. In the intact and castrated males kidney stones were present and the kidney Ca contents were over 20 times as high as in the controls, but in the corresponding females no increases in Ca levels compared to those of the controls and no stones were observed. Female hormone when administered to both intact and castrated rats prevented stone formation and reduced kidney Ca levels to those of the control or female animals. No stones nor any effect on the Ca levels resulted from the injection of male hormone in intact females. Stones were however formed in castrated females and the Ca content of the kidney was raised to a level intermediate between those arising from the ingestion of I by intact males and females. The formation of kidney stones and exhibition of raised kidney Ca levels on continued ingestion of I was therefore normally confined to the male rat, under the conditions of these experiments. Rats treated with hormones of the opposite sex however tended to reflect the characteristics of the opposite rather than their own sex in relation to the effect on the kidney of I. Tanret, P., Thomas, J., Thomas, E. & Cottenot, F. (1962). Influence du sexe sur les formations de d~p6ts d'oxalate de calcium dans les reins chez le Rat intoxique par l'rthyl~ne-glycol. C.R. Soc. BioL, Paris 156, 1285.
276. Electron microscopic studies on diethylene glycol poisoning Electron microscopy has been employed to investigate the early effects in the rat of single doses of 15-25 ml diethyleneglycol (I)/kg on the proximal convoluted tubules of the kidney, and of 7.5-10 ml carbon tetrachloride (II)/kg on the cells of the liver. 30 min after I was administered, the mitochondria of the epithelial cells of the renal tubules were seen to be swollen. Breakdown of the internal lateral walls (cristae) of the mitochondria occurred and vacuoles appeared within these organelles after 3 hr. Up to this stage use of the light microscope failed to reveal these changes. At 12-24 hr larger vacuoles appeared in the cells due partly to the invagination of the basal parts of the cytoplasm and partly to an increase in size of the lumina of the rough-surfaced endoplasmic reticulum. A partial loss of the surface granules of the reticular membranes was also observed. Vacuole formation was also noted in the cells of the distal convoluted tubules at 24 hr. Swelling and vacuolation of the mitochondria, although less pronounced, was also the earliest change produced by II in the fiver cells. The most obvious change however occurred at 12 hr and consisted of the appearance of large vacuoles within the cell cytoplasm due to the enlargement of the space within the endoplasmic reticulum. [Our readers must forgive the technical terminology, which cannot readily be .explained in simple language. The crux of the matter is that, by using the electron microscope, one can detect morphological changes much earlier after the onset of toxic action. These changes might well be missed by other present-day methods. Nevertheless the huge doses used by the author are indicative of the sledge-hammer approach which we decry. It is obvious that more subtle tests are called for.]