Arch Toxicol (1992) 66:198-203
Archives of
Toxicology 9 Springer-Verlag 1992
Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats Koji Mori 1, Masanobu Kaido 2, Kazuya Fujishiro t , Naohide Inoue 1, and Osamu Koide2 1 Department of Environmental Toxicology, Institute of Industrial Ecological Sciences, and 2 Department of Pathology and Surgical Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807, Japan Received 18 April 199t/Received after revision 3 September 1991/Accepted 5 September 1991
Abstract. Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and ~-glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat. Key words: Pyridoxine- Vitamin B6 - Testis - Reproductive system - Spermatogenesis - Rat
the active form of vitamin B6 and acts as a coenzyme for many decarboxylation and transamination reactions (Holtz and Palm 1964). Although the minimum daily requirement for n0rmal adults is 2 to 4 mg, megadoses of pyridoxine (600-4000 mg/day) have been used in some therapeutic applications including homocystinuria (Barber and Spaeth 1969; Carson and Carte 1969; Mudd et al. 1970), premenstrual syndrome (Abraham and Hargrove 1980), autistic children (Rimland et al. 1978), carpal tunnel syndrome (Ellis et al. 1981) and galactorrhea-amenorrhea syndrome (McIntosh 1976). Since Schaumburg et al. (1983) reported a case, there has been an increasing number of reports in the literature suggesting that a high-dose administration of pyridoxine induced sensory neuropathy in humans (Cohen and Bendich 1986). Recently, it has been indicated thai many neurotoxicants, such as 2,5-hexanedione, acrylamide, lead, cadmium, tri-o-cresyl phosphate and ethylene oxide also cause reproductive toxicity (reviewed by Chapin et al. 1990). With regard to pyridoxine, however, the other adverse effects of pyridoxine, including those on the sexual organs, have not been documented. In the present study, we investigated the effects of megadoses of pyridoxine on the male reproductive system. We measured sexual organ weights, mature spermatid counts in the testis, sperm counts in the epididymis, plasma testosterone concentration and some marker enzymes of the testicular cells as endpoints, since we could evaluate both the functions of seminiferous tubules and Leydig cells without histopathological examinations.
Materials and methods Introduction Pyridoxine (vitamin B6) is an essential and water-soluble vitamin. It is metabolized to pyridoxal phosphate, which is Offprint requests to: Koji Moil
Chemicals. Pyridoxine hydrochloride was purchased from Wako Pure Chemicals Industries Ltd. (Osaka, Japan). All chemicals used were of reagent grade. Animals. Male Wistar rats, approximately 8 weeks of age, were obtained
from Seiwa Experimental Animals Ltd (Fukuoka, Japan). They were acclimated to our laboratory conditions for 5 weeks, and divided into five groups, the control, 125 mg/kg, 250 mg/kg, 500 mg/kg and 1000 mg/kg
199 i 500
0 n'~J/kg ~, 125 mg/kg 9 250 mg/kg A 500 rng/kg 9 1,000 mg/kg o
3O{
Exposure period (weeks) fig. 1. Effects of pyridoxine on body weight gain. Each point indicates the mean of each group. The number of experiments is six in all the groups at 2 weeks, or nine in the control, seven in the 1000 mg/kg or six in the other groups at 6 weeks. Significantly different from control, *p
Archives of
Toxicology 9 Springer-Verlag 1992
Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats Koji Mori 1, Masanobu Kaido 2, Kazuya Fujishiro t , Naohide Inoue 1, and Osamu Koide2 1 Department of Environmental Toxicology, Institute of Industrial Ecological Sciences, and 2 Department of Pathology and Surgical Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807, Japan Received 18 April 199t/Received after revision 3 September 1991/Accepted 5 September 1991
Abstract. Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and ~-glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat. Key words: Pyridoxine- Vitamin B6 - Testis - Reproductive system - Spermatogenesis - Rat
the active form of vitamin B6 and acts as a coenzyme for many decarboxylation and transamination reactions (Holtz and Palm 1964). Although the minimum daily requirement for n0rmal adults is 2 to 4 mg, megadoses of pyridoxine (600-4000 mg/day) have been used in some therapeutic applications including homocystinuria (Barber and Spaeth 1969; Carson and Carte 1969; Mudd et al. 1970), premenstrual syndrome (Abraham and Hargrove 1980), autistic children (Rimland et al. 1978), carpal tunnel syndrome (Ellis et al. 1981) and galactorrhea-amenorrhea syndrome (McIntosh 1976). Since Schaumburg et al. (1983) reported a case, there has been an increasing number of reports in the literature suggesting that a high-dose administration of pyridoxine induced sensory neuropathy in humans (Cohen and Bendich 1986). Recently, it has been indicated thai many neurotoxicants, such as 2,5-hexanedione, acrylamide, lead, cadmium, tri-o-cresyl phosphate and ethylene oxide also cause reproductive toxicity (reviewed by Chapin et al. 1990). With regard to pyridoxine, however, the other adverse effects of pyridoxine, including those on the sexual organs, have not been documented. In the present study, we investigated the effects of megadoses of pyridoxine on the male reproductive system. We measured sexual organ weights, mature spermatid counts in the testis, sperm counts in the epididymis, plasma testosterone concentration and some marker enzymes of the testicular cells as endpoints, since we could evaluate both the functions of seminiferous tubules and Leydig cells without histopathological examinations.
Materials and methods Introduction Pyridoxine (vitamin B6) is an essential and water-soluble vitamin. It is metabolized to pyridoxal phosphate, which is Offprint requests to: Koji Moil
Chemicals. Pyridoxine hydrochloride was purchased from Wako Pure Chemicals Industries Ltd. (Osaka, Japan). All chemicals used were of reagent grade. Animals. Male Wistar rats, approximately 8 weeks of age, were obtained
from Seiwa Experimental Animals Ltd (Fukuoka, Japan). They were acclimated to our laboratory conditions for 5 weeks, and divided into five groups, the control, 125 mg/kg, 250 mg/kg, 500 mg/kg and 1000 mg/kg
199 i 500
0 n'~J/kg ~, 125 mg/kg 9 250 mg/kg A 500 rng/kg 9 1,000 mg/kg o
3O{
Exposure period (weeks) fig. 1. Effects of pyridoxine on body weight gain. Each point indicates the mean of each group. The number of experiments is six in all the groups at 2 weeks, or nine in the control, seven in the 1000 mg/kg or six in the other groups at 6 weeks. Significantly different from control, *p
