[Ototoxic effect of BB-K8 administered to pregnant guinea pigs on development of inner ear of intrauterine litters (author's transl)].
Transplacental ototoxic effects of BB-K8 on development of inner ear in intrauterine guinea pigs were evaluated by differential frequency pinna reflex test in range of 20 kHZ to 500 HZ and histopathological examination of spiral and vestibular organs in new born guinea pigs from pregnant ones given BB-K8 i.m. during gestation.


METHODS
Twenty-five pregnant guinea pigs of the Hartley strain and 63 new-born guinea pigs from the pregnant ones were used in the study. Following antibiotics were given i.m. daily to the 20 pregnant guinea pigs from 7th day of gestation for 56 days. BB-K8 was given at the dose level of 100 mg/kg and 200 mg/kg, respectively. Kanamycin (KM) was administered at the dose level of 100 mg/kg and 200 mg/kg, respectively. Physiological saline solution (1.0 ml/kg) was given i.m. to the pregnant guinea pigs for 56 days. The differential frequency pinna reflex test was performed in the frequency range from 20 kHZ to 500 HZ to determine an extent of frequency of pinna reflex loss. The test was carried out before the start of administration of the antibiotics and once a week during the administration. After the last injection of the antibiotics, intravital perfusion fixation was carried out in the new born animals under anesthesia with nembutal. Histopathological examination was made in celloidin serial sections of the cochlea and vestibulum of the new born animals to observe an extent or degree of hair cell damage.


RESULTS
(1) The differential frequency pinna reflex test revealed that new born guinea pigs from the pregnant ones given BB-K8 and KM respectively at the dose level of 100 mg/kg did not show occurrence of pinna reflex loss at any frequency tested. At the dose level of 200 mg/kg, BB-K8 did not result in transplacental hearing impairment in new born guinea pigs, but KM caused transplacental pinna reflex loss in the highest frequencies from 20 k to 15 kHZ in 3 of 10 animals. (2) Histopathological examination detected that unilateral incomplete loss of outer hair cells of the spiral organ confined to the basal end of cochlea was found in 3 of 13 new born guinea pigs from the pregnant ones treated with BB-K8 (100 mg/kg). In the animals, slight damage of hair cells in the vestibular organs occurred in 100%. These hair cell damages were enhanced slightly in the new born guinea pigs from the pregnant ones treated with BB-K8 (200 mg/kg) and much more in the new born ones from the pregnant ones treated with KM (100 mg/kg, 200 mg/kg). (3) These results suggest that BB-K8 has a mild potency to cause transplacental ototoxic damage in the inner ear of intrauterine guinea pigs within the pregnant ones treated for 56 days (normal gestation period approximately 70 days).
D000583:Amikacin / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D007758:Ear, Inner / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006168:Guinea Pigs; D007612:Kanamycin / Q000031:analogs & derivatives*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012018:Reflex / Q000187:drug effects
D007612:Kanamycin; D000583:Amikacin