Biomedical subjects

M Kaneto

Publications and source records attributed to M Kaneto.

7 recordsLinked to original sources

PubMed2001

Collaborative study on rat sperm motion analysis using CellSoft Series 4000 semen analyzer.

A collaborative study was conducted to determine useful and sensitive rat sperm motion parameters in a CellSoft Series 4000 semen analyzer to detect the effects of compounds on sperm motion. The effects on the sperm motion parameters were investigated using alpha-chlorohydrin, boric acid, ethinylestradiol, ethyl methanesulfonate, nitrazepam, nitrobenzene, ornidazole, sulfasalazine or valproic acid which are well known to induce reproductive or testicular toxicities. All compounds used in this study decreased percentage of motile sperm (% motile). Curvilinear velocity (VCL), maximum and mean amplitude of lateral head displacement (ALH max and ALH mean) were decreased by treatment with all compounds except for valproic acid. Treatment with alpha-chlorohydrin, ornidazole or sulfasalazine under mid-dosage regimens decreased only these parameters. Beat cross frequency (BCF) was increased by treatment with sulfasalazine. There were some treatments which caused either decreased or increased changes irrespective of dosage regimen in linearity, average radius, percentage of circular-swimming sperm out of motile sperm (circular/motile) and percentage of circular-swimming sperm out of all sperm (circular/all). Based on these results, we concluded that % motile, VCL, ALH max and ALH mean are considered useful and sensitive parameters for evaluating the effects of compounds on sperm motion. A parameter of BCF can be useful to detect the effects of specific compounds on sperm motion. Linearity, average radius, circular/motile and circular/all are not considered useful or sensitive indicators to detect the effects of compounds on sperm motion.

Animals↗

PubMed2001

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (1)--A study on oral administration prior to and in the early stages of pregnancy in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to rats at doses of 100, 300 or 1000 mg potency/kg/day prior to and in the early stage of pregnancy to assess its adverse effects on parental reproductive ability and embryo-fetal development. Loose and/or reddish brown feces were observed in both males and females of all the S-1090 dosing groups, and abdominal distention was also observed in males throughout the dosing period. No drug-related deaths occurred in either males or females. In males, body weight and food consumption were increased at a dose of 1000 mg potency/kg/day throughout the dosing period. In females, body weight gain was restrained during late pregnancy, and food consumption was decreased transiently following the initiation of dosing, and then remained high on the day before parturition in all the S-1090 dosing groups. Necropsy of male and female rats revealed an increase in the cecum weight. The reproductive ability of males and females was normal in all the S-1090 dosing groups. No effects of S-1090 were observed in the implantation ratio, embryo-fetal viability, fetal body weight, and incidence of external, skeletal and visceral anomalies. Based on these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for parental general toxicity, 1000 mg potency/kg/day for reproductive toxicity, and 1000 mg potency/kg/day for developmental toxicity in embryo-fetuses under the conditions of the present study.

Administration, Oral↗

PubMed2001

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (2)--A study on oral administration during the period of organogenesis in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Days 7 to 17 of pregnancy to assess its effects on dams and on development of the embryo-fetuses and offspring. Loose or reddish-brown feces were observed in dams of all the S-1090 dosing groups. Body weight gain was increased from the early stage of administration to the end of pregnancy, food consumption was transiently decreased at the early stage of administration, and water consumption was increased from the middle to the end of pregnancy in all the S-1090 dosing groups. However, no effects on pregnancy, parturition and lactation were observed. Necrospy revealed an increased cecum weight in pregnant and lactating dams of all the S-1090 dosing groups. No effects of S-1090 were observed in viability, growth, incidences of external, skeletal and visceral anomalies, and degree of ossification in F1 fetuses. No effects of S-1090 were observed in such parameters as viability, incidence of external and skeletal anomalies, physical development, sensory functions/reflexes, behavior and reproductive function in F1 offspring. No adverse effects were observed in F2 offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, 1000 mg potency/kg/day for maternal reproductive toxicity and the developmental toxicity in the embryo-fetuses and offspring under the conditions of the present study.

Abnormalities, Drug-Induced↗

PubMed2001

[Reproductive and developmental toxicity studies of S-1090, cefmatilen hydrochloride hydrate (4)--A study on oral administration during the perinatal and lactation periods in rats].

Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Day 17 of pregnancy to Day 20 of lactation to assess its effects on pregnant/lactating females and on development of the offspring. In dams, loose feces/reddish brown feces, increased cecum weight, decreased weights of the heart, spleen and submaxillary gland in all the S-1090 dosing groups and a decreased weight of the thymus in the 1000 mg potency/kg dosing group were observed. However, no effects on parturition and lactation were observed in any of the dosing groups. In F1 offspring, although increased cecum weight was found at weaning in all the S-1090 dosing groups, no abnormalities in viability, physical development, sensory functions/reflexes, behavior and reproductive function were observed. No adverse effects were observed in F2 fetuses and offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, and 1000 mg potency/kg/day for maternal reproductive toxicity and for developmental and reproductive toxicity in offspring under the conditions of the present study.

Administration, Oral↗

PubMed1999

Characterization of epididymal sperm motion and its correlation with stages of target cells in rats given alpha-chlorohydrin, cyclophosphamide or nitrazepam.

Epididymal sperm motion in rats was characterized by computer-aided sperm motion analysis (CASA) with its correlation to testicular lesions in the 2-week treatment study, using three compounds which are known to affect different stages of germ cells. Mature male rats were treated daily for 2 weeks with alpha-chlorohydrin (alpha-CH, 5 mg/kg), cyclophosphamide (CP, 20 mg/kg) or nitrazepam (NZ, 20, 40, 60 mg/kg). Changes in sperm motion were detected only in the alpha-CH and 60-mg/kg NZ-treated groups. Of the sperm motion parameters, velocity and amplitude of lateral head displacement (ALH) were concomitantly reduced in these two groups with good correlation. With respect to the distribution of the values in parameters, however, alpha-CH shifted the values down within a small range with high percentages of motile sperm, while NZ distributed them over a wide range with low percentages of motile sperm. CP treatment showed no histopathological changes in advanced germ cells, though it showed a decrease in the number of early germ cells. NZ treatment affected round and elongating spermatids (approximately step 14) at doses of 20 and 40 mg/kg, and affected also more advanced spermatids (approximately step 19) at the dose of 60 mg/kg. alpha-CH treatment did not affect testicular histopathology. These findings indicate that 60-mg/kg NZ treatment reduced sperm motion as a result of lesions affected in elongated spermatids and alpha-CH reduced it by direct effects on epididymal spermatozoa. The present study indicates that in addition to percentage of motile sperm, the velocity and ALH can be useful to detect the changes in sperm motion caused by different actions of NZ and alpha-CH, though each compound showed a distinct distribution pattern of these parameters.

Animals↗

PubMed1985

Radiolytic hydroxylation of 1-substituted thymines promoted by transition metal salts in N2- and N2O-saturated aqueous solutions.

The effect of high-valent transition metal salts on the radiation-induced hydroxylation of thymine (1a), 1-methylthymine (1b), and thymidine (1c) to the corresponding thymine glycol derivatives (2a-c) was studied at pH 7.0 in N2- and N2O-saturated aqueous solutions. The selectivities of (2a-c) based on converted (1a-c) increased to attain the maxima of 35-69% and then decreased, with increasing the one-electron reduction potential [E(M (n+1)+/Mn+)] of metal salts in the range of 0-1.0 V vs. NHE less than. Metal salts with E(M (n+1)+/Mn+) 0 or greater 1.0 V vs. NHE caused little change in the yields of (2a-c).

Hydroxylation↗

PubMedDate not supplied

Epididymal sperm motion as a parameter of male reproductive toxicity: sperm motion, fertility, and histopathology in ethinylestradiol-treated rats.

The present study was designed to characterize the effect of ethinylestradiol (EE) on epididymal sperm motion using a computer-assisted sperm analysis system (CASA), and to elucidate the correlation between sperm motion endpoints and other measures including fertility, histopathologic, and endocrinologic endpoints. EE was orally given to adult male rats at a daily dosage of 10 mg/kg for 3 and 5 d, and at daily dosages of I and 10 mg/kg for 1, 2, 3, and 4 weeks. Changes in sperm motion were first detected after one week of treatment. Of nine sperm motion parameters, the percentage of motile sperm, velocity, and amplitude of the lateral head displacement (ALH) were decreased in the 10 mg/kg dosing group. Accompanying the decreases in those parameters, the male fertility indices in the 10 mg/kg dosing group were reduced after one week of treatment, and no males in this group could impregnate intact females after 2 weeks or more of treatment. The number of sperm heads in the cauda epididymis in the 10 mg/kg dosing group was reduced to about one-half that in the control group after one week of treatment, whereas the total number of homogenization-resistant advanced spermatids in the testis was not altered and only a slight change was detected in the number and morphology of germ cells in the testis. These results suggest that reduction in the number of epididymal sperm and in sperm motion are not secondary to testicular alteration. However, after 3 weeks of treatment, the number of sperm heads in the testis was drastically reduced with severe atrophy of the seminiferous tubules both in the 1 and 10 mg/kg dosing groups. The profiling of epididymal luminal fluid proteins indicated that two major bands that migrated with molecular weights of about 22 and 23 kDa were weakened and their density was reduced to approximately 70% of the control after 5-d and one week treatments in the 10 mg/kg dosing group. Circulating testosterone declined drastically after 3 d of treatment and remained at undetectable levels with a concomitant decline of circulating LH and FSH, suggesting that EE inhibits testosterone secretion immediately via a negative feedback system, and there follow changes in the accessory reproductive organs including the epididymis. These results indicate that EE affects epididymal spermatozoa before testicular germ cells via a testosterone deficiency, when it is administered at extremely high dosages. The reduction in the sperm motion manifested as decreases in the percentage of motile sperm, ALH, and velocity, is considered to be responsible for the onset of infertility. Sperm motion analysis could be particularly useful for detecting the toxic effects of chemicals that act through the endocrinologic system on the epididymis.

Animals↗