A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse
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概要
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The present study was designed to investigate testicular effects of Acyclovir [9-(2-hydroxyethoxymethyl)-9H-guanine] in mouse. Swiss albino male mice (N=6/group/dose/sample time) were treated (i.p.) every day with 4, 16, 32, and 48mg/kg body weight of Acyclovir for 15d. The testis was examined for histopathological changes and the seminiferous tubular diameter (STD) and epithelial height (SE) were measured. The sperm count, sperm motility and sperm morphology assay in caudae epididymes, and intra-testicular levels lactate dehydrogenase (LDH) and testosterone were estimated on 7d, 14d, 21d, 28d, 35d, and 70d, following the last exposure. Acyclovir did not affect the body weight, but decreased the testis weight on 21d and 28d at two higher dose-levels, and on 35d at all dose-levels. The STD was decreased on 21d at 16-48mg/kg dose-levels (p<0.01), on 28d and 35d, at all dose-levels (p<0.01-0.001). The SE was decreased on 14d at two higher dose-levels (p<0.01), thereafter up to 35d at all dose-levels (p<0.001). Acyclovir decreased the sperm count from 7-35d (p<0.001) with a recovery observed on 70d, except at 48mg/kg dose-level (p<0.05), and inhibited the sperm motility (p<0.001) from 7-35d with a maximum effect on 28-35d. On the other hand, sperm abnormalities increased on 21d, 28d and 35d at 16-48mg/kg, at 32-48mg/kg, and at 32mg/kg dose-levels, respectively (P<0.05). LDH activity was increased (p<0.05-0.001) from 7d (except at 4mg/kg) to 35d. Only 48mg/kg dose group showed increase in LDH concentration on 70d. In conclusion, Acyclovir is cytotoxic to germ cells inducing the cellular destruction, and reducing the sperm count and motility, and increasing sperm abnormalities. Further, Acyclovir also caused cellular destruction thus releasing LDH from the cells, and affecting the Leydig cell function. All adverse effects of Acycovir are reversible by 70d, except the sperm count and LDH level, which appear to be affected over an extended period of time at a higher dose-level.
- 日本トキシコロジー学会の論文
- 2008-02-15
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- A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse