Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats aged 10 days (Exp. A), 45 days (Exp. B) and 70-90 days (Exp. C) were given procarbazine intraperitoneally at doses of 30 mg/kg/day for 5 or 9 weeks (Exps A, B, C), or by gavage at doses of 5 mg/kg/day (equivalent to the therapeutic dose in man) and 50 mg/kg/day, for 9 weeks (Exp. B). A significant mortality rate was noted in immature rats (Exp. A) and in animals receiving 50 mg/kg/day orally (Exp. B). In all groups the rate of body weight gain and the weights of the testes and epididymides were reduced. Procarbazine produced disruption of the normal spermatogenetic architecture that was very severe or total in immature rats (Exp. A) and in rats given the drug at 30 mg/kg/day for 9 weeks and the highest dose (50 mg/kg) in Exp. B. Disruption of spermatogenesis was only partial in the other experimental groups. The number of Sertoli cells was not affected by the different treatments, but a Sertoli cell dysfunction (vacuolization, decreased ABP and elevated FSH concentrations), most probably secondary to germ cell degeneration, was demonstrated in those rats presenting the most severe disruption of spermatogenesis (Exp. B: i.p. and gavage, 50 mg/kg for 9 weeks). Leydig cells, always present in the interstitium, were moderately affected (decrease in serum testosterone values) in some groups at all ages whereas epididymal sperm reserves were decreased after 9 weeks (Exp. B: 30 mg/kg, i.p.; 5 and 50 mg/kg, gavage). Moreover, there was a marked fall in the number of fetuses per female mated by males in all experimental groups. We conclude that the effects of procarbazine on male reproductive function were independent of the route of administration, greater before puberty and proportional to the dose administered as well as to the duration of the treatment.
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PMID:Reproductive effects of the anti-cancer drug procarbazine in male rats at different ages. 318 60

Procarbazine has been implicated as a cause of infertility. Regionalization of drug delivery is a potential method to avoid this problem. We investigated the protective effect of testicular circulatory isolation (TCI) on gonadal toxicity during procarbazine administration in the Sprague-Dawley rat. Four groups (n = 10/group) were used. Animals in group 1 received no treatment. Rats in groups 2 and 3 were anaesthetized and received TCI of the left testis by clamping of the spermatic cord and gubernaculum immediately before a bolus of intravenous procarbazine (400 mg kg-1). The clamping was maintained for 15 min after procarbazine administration in group 2 and for 45 min in group 3. Rats in group 4 received sham surgery immediately before procarbazine administration. On day 70, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurements of testicular weight, sperm head count, repopulation index, and epididymal index. The results indicated that 15 min of TCI did not mitigate testicular toxicity; 45 min of TCI provided moderate protection against procarbazine-induced testicular toxicity.
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PMID:Regional procarbazine delivery reduces testicular toxicity. 813 Sep 42