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Alloxan toxicity in human and canine spermatozoa. Possible biochemical basis for a species difference in sensitivity
Abstract:
In view of the well known species differences in the sensitivity of pancreatic B-cells to the toxic glucose analogue alloxan, it was tested whether spermatozoa from two species with a different diabetogenic effect of alloxan displayed a similar difference in their sensitivity to this drug. In canine spermatozoa, less than 2 mM alloxan profoundly reduced the rate of glucose oxidation and cellular motility whereas more than 5 mM was required to significantly alter these parameters in human spermatozoa. Such species difference was not observed in spermatozoal sensitivity towards the inhibitory effects of tert-butyl hydroperoxide. The phenomenon is not attributable to a different rate of alloxan uptake since the drug is not incorporated by dog or human spermatozoa. The alloxan toxicity was counteracted by D-glucose and its 3-O-methyl analogue in both species, and was potentiated by ascorbic acid; however, only in man. The protective effect of D-glucose was much less marked in tert-butyl hydroperoxide-cytotoxicity. It is concluded that the observed species difference in spermatozoal alloxan sensitivity is not related to differences in alloxan uptake or in sensitivity to organic peroxides; differences in cellular scavenging of superoxide anion radicals and/or ascorbic acid metabolism may explain the lower sensitivity of human spermatozoa for alloxan.
Insights
Canine spermatozoa are more sensitive to the toxic glucose analogue alloxan than human spermatozoa. This species difference in alloxan sensitivity is not due to uptake or peroxide sensitivity, but may involve radical scavenging or ascorbic acid metabolism.
Area of Science:
- Biochemistry
- Toxicology
- Reproductive Biology
Background:
- Species-specific sensitivity to alloxan is known for pancreatic B-cells.
- Alloxan is a toxic glucose analogue used to induce diabetes in research models.
Purpose of the Study:
- To investigate species differences in spermatozoal sensitivity to alloxan.
- To compare canine and human spermatozoa responses to alloxan and tert-butyl hydroperoxide.
Main Methods:
- Spermatozoa from dogs and humans were exposed to varying concentrations of alloxan and tert-butyl hydroperoxide.
- Glucose oxidation and cellular motility were measured.
- Alloxan uptake was assessed.
Main Results:
- Canine spermatozoa showed significantly reduced glucose oxidation and motility at <2 mM alloxan, while human spermatozoa required >5 mM.
- No species difference was observed in sensitivity to tert-butyl hydroperoxide.
- Alloxan uptake was negligible in both species.
- D-glucose protected against alloxan toxicity in both species, while ascorbic acid potentiation occurred only in humans.
Conclusions:
- Species-specific alloxan sensitivity in spermatozoa is not explained by uptake or peroxide sensitivity.
- Differences in cellular superoxide anion radical scavenging and/or ascorbic acid metabolism may account for the lower sensitivity of human spermatozoa to alloxan.