Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anticancer and immunosuppressive drug cyclophosphamide is extensively used in clinical practice and is known to alter fertility in man. We showed previously that treatment of male rats with low daily doses of cyclophosphamide over a 9-week period caused fetal malformations, a high rate of postimplantation loss and affected epididymal and sperm histology. In the present study, five biochemical measures of epididymal function were used to characterize further the effects of cyclophosphamide on the epididymis. For 1, 3, 6, or 9 weeks, adult Sprague-Dawley rats were gavage-fed daily with saline (control), 5.1 (low dose), or 6.8 (high dose) mg/kg of cyclophosphamide. The specific activities of the two glycolytic enzymes aldolase and lactate dehydrogenase (LDH), the mitochondrial enzyme succinate dehydrogenase, the cytosolic enzyme carnitine acetyltransferase and the lysosomal enzyme acid phosphatase were determined in cytosolic and mitochondrial subcellular fractions from four segments of the epididymis. Cyclophosphamide caused decreases in protein concentrations in all segments of the epididymis only after 6 weeks of treatment with the high dose. The specific activities of aldolase, LDH and succinate dehydrogenase did not differ from control with respect to dose or duration of treatment. In contrast, there were significant effects of cyclophosphamide on carnitine acetyltransferase and acid phosphatase specific activity. After 1 week of treatment, there was a transient dose-related decrease in the specific activity of carnitine acetyltransferase, which was most striking for the corpus epididymidis (76% of control), but which did not differ from control after 3, 6, and 9 weeks. After 6 weeks of treatment with the high dose of cyclophosphamide, carnitine acetyltransferase specific activity in the initial segment and the corpus epididymidis was elevated to 165 and 140%, respectively, as compared with the 1-week high dose values. The specific activity of acid phosphatase did not differ from control after 1 and 9 weeks of treatment. At 3 and 6 weeks, however, there was a dose-related increase in acid phosphatase specific activity for all regions of the epididymis that was most marked in the cauda after the 6-week treatment (140% of control). Therefore, low dose, daily treatment of male rats with cyclophosphamide not only alters specific enzymes in specific segments of the epididymis, but acts in a dose- and time-dependent manner. It is possible that these changes could be mediated by direct, toxic effects of the drug on the epithelium or be secondary to alterations in the spermatozoa as a result of the treatment.
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PMID:Effects of cyclophosphamide on selected cytosolic and mitochondrial enzymes in the epididymis of the rat. 338 43

Rhabdomyolysis is an unusual complication of hematopoietic stem cell transplantation (HSCT). Cyclophosphamide has been one of the key drugs in the most common preparative regimen for HSCT. We present here a rare case of acute rhabdomyolysis following administration of high-dose cyclophosphamide. A 47-year-old woman with adult T-cell leukemia in remission was treated with high-dose cyclophosphamide as a preparative regimen for allogeneic bone marrow transplantation. Nineteen hours later, general convulsions and acidosis suddenly occurred. Levels of serum creatine kinase (skeletal muscle type), myoglobin, and aldolase were markedly elevated to 32870 IU/l, 640 ng/ml, and 240.3 IU/l, respectively. Rhabdomyolysis caused by high-dose cyclophosphamide was diagnosed, and the preparative chemotherapy was discontinued. Subsequently, her muscular signs and symptoms improved, and the results of laboratory examinations returned to normal after 2 weeks. She had previously been treated with conventional doses of cyclophosphamide, doxorubicin, vincristine, and prednisolone without evidence of rhabdomyolysis. Acute rhabdomyolysis may be an adverse effect specific to high-dose cyclophosphamide therapy.
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PMID:Acute rhabdomyolysis following administration of high-dose cyclophosphamide: case report. 1180 38