Effect of tacrolimus on the cauda epididymis in rats: analysis of epididymal biochemical markers or antioxidant defense enzymes.
The effect of tacrolimus on epididymal biochemical markers was investigated following single daily subcutaneous doses of 1, 2 and 3 mg kg(-1) day(-1) for 2 weeks to male adult rats. The tacrolimus 2 and 3 mg kg(-1) day(-1) groups showed a significant and dose-dependent decrease in sperm count in the cauda epididymis. Among tissue levels of L-carnitine, alpha-glucosidase and acid phosphatase, only L-carnitine level in the cauda epididymis was significantly reduced in the tacrolimus 3 mg kg(-1)day(-1) group. However, no significant difference was seen in the plasma L-carnitine. It was suggested that lowering of L-carnitine in the cauda epididymis was attributable to the adverse effect on epididymal function to transport and/or concentrate L-carnitine. Since L-carnitine has been reported to have antioxidant potential, antioxidant defense enzymes in the cauda epididymis such as superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione reductase were evaluated. The results showed no significant differences in activities, confirming that the treatment with tacrolimus did not affect the activities of these antioxidant enzymes. In conclusion, this study indicates that tacrolimus induces a decrease in L-carnitine level in the cauda epididymis, which is probably caused by impairment of epididymal function to transport and/or concentrate L-carnitine from bloodstream, and a decrease in sperm count.
Hisatomi
Akihiko
A
Drug Safety Research Laboratories, Astellas Pharma Inc., 1-6 Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan. akihiko.hisatomi@jp.astellas.com
Sakuma
Shozo
S
Fujiwara
Michio
M
Seki
Jiro
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000097:blood / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013076:Sperm Count; D013482:Superoxide Dismutase / Q000378:metabolism; D016559:Tacrolimus / Q000009:adverse effects*
D000975:Antioxidants; D015415:Biomarkers; D007166:Immunosuppressive Agents; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D002331:Carnitine; D016559:Tacrolimus