ABSTRACT
The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2-microglobulin. A slight increase with ribostamycin was observed in alpha-fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days.
Subject(s)
Anti-Bacterial Agents/toxicity , Gentamicins/toxicity , Kidney Diseases/chemically induced , Ribostamycin/toxicity , Animals , Enzymes/urine , Gentamicins/metabolism , Kidney/pathology , Kidney/physiopathology , Kidney Cortex/metabolism , Kidney Diseases/physiopathology , Kidney Diseases/urine , Kidney Medulla/metabolism , Male , Polyuria/chemically induced , Proteinuria/chemically induced , Rats , Ribostamycin/metabolism , Urine/cytologyABSTRACT
The effect of dactimicin on the inner ear of guinea pigs was investigated by comparing it with the effects of ribostamycin, astromicin and amikacin. At doses of 200 and 400 mg/kg/day for 4 weeks, no pinna reflex loss was observed, but 2 animals receiving 400 mg dactimicin/kg/day showed unilateral loss of the outer hair cells in the cochlea and very scattered loss of the hair cells in the vestibular organ. At doses of 400 and 500 mg dactimicin/kg/day for 5 weeks, all surviving animals showed no abnormality of the outer hair cells, the inner hair cells and the spiral ganglion cells in the cochlea except for scattered unilateral loss of the outer hair cells and loss of the stria vascularis. Based on these observations, it is concluded that the ototoxicity of dactimicin on the inner ear of guinea pigs is the same as or a little stronger than that of ribostamycin, weaker than or the same as that of astromicin and weaker than amikacin.
Subject(s)
Amikacin/toxicity , Aminoglycosides , Anti-Bacterial Agents/toxicity , Cochlea/drug effects , Ear, Inner/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Cochlea/ultrastructure , Guinea Pigs , Male , Microscopy, Electron, Scanning , Ribostamycin/toxicity , Vestibule, Labyrinth/drug effectsABSTRACT
The vestibular toxicities of dibekacin, ribostamycin, gentamicin, and streptomycin were compared in guinea pigs. The animals were given the drugs for 21 days, examined for functional disturbances by electronystagmography (ENG), and then killed to observe morphologic changes in the vestibular sensory hairs on scanning electron microscopy (SEM). The degree of functional impairment was rated according to the duration of the postrotatory nystagmus and classified into three categories: normal, slight impairment, and severe impairment. The results of the SEM examination were similarly classified into three categories by severity of the degenerative changes in the vestibular sensory hairs, i. e., bending, fusion, ballooning, giant hair formation, or disappearance. Under these experimental conditions, the results of ENG and SEM observations showed good correlation and indicated that the vestibular toxicity was highest in the streptomycin-treated animals and lowest in the dibekacin- or ribostamycin-treated animals.
Subject(s)
Anti-Bacterial Agents/toxicity , Dibekacin/toxicity , Kanamycin/analogs & derivatives , Saccule and Utricle/drug effects , Vestibule, Labyrinth/drug effects , Aminoglycosides/toxicity , Animals , Electronystagmography , Guinea Pigs , Microscopy, Electron, Scanning , Ribostamycin/toxicity , Saccule and Utricle/ultrastructure , Vestibule, Labyrinth/ultrastructureABSTRACT
The cochlear toxicities of six aminoglycoside antibiotics were functionally and morphologically evaluated in guinea pigs. Forty-six Hartley strain guinea pigs were allocated into seven groups, including a control, and given intramuscular injections of one of the drugs or saline solution daily for 28 days. The hearing thresholds of all the animals were measured by the differential frequency pinna reflex test before, during, and after treatment to assess changes in cochlear function. Scanning electron microscopy was used to examine morphological changes in the cochlea after treatment and to detect degenerative changes in the auditory hairs of the basal turn. The results obtained from the functional and morphological examinations were well correlated, indicating the most severe changes in animals given gentamicin followed, in order, by amikacin, tobramycin, kanamycin, dibekacin, and ribostamycin.
Subject(s)
Anti-Bacterial Agents/toxicity , Cochlea/ultrastructure , Dibekacin/toxicity , Kanamycin/analogs & derivatives , Amikacin/toxicity , Aminoglycosides/pharmacology , Aminoglycosides/toxicity , Animals , Anti-Bacterial Agents/pharmacology , Cochlea/drug effects , Gentamicins/toxicity , Guinea Pigs , Kanamycin/toxicity , Ribostamycin/toxicity , Tobramycin/toxicityABSTRACT
Ribostamycin ototoxicity was tested in a group of 28 albino guinea-pigs of both sexes, body-weight about 250-450 g with auricular Prayer's reflex present. The mounting of the cochlea on a metal support and the scanning electron microscope observations are described, The cochleacytogram of the group treated daily with 200 mg/kg ten days consecutively is comparable to that of the non-treated group.
Subject(s)
Anti-Bacterial Agents/toxicity , Cochlea/drug effects , Ribostamycin/toxicity , Animals , Cochlea/ultrastructure , Female , Guinea Pigs , Hair Cells, Auditory/ultrastructure , Hair Cells, Auditory, Inner/ultrastructure , Labyrinth Supporting Cells/ultrastructure , Male , Microscopy, Electron, Scanning , Organ of Corti/ultrastructureABSTRACT
The effects of three aminoglycoside antibiotics on the rat isolated phrenic nerve-diaphragm preparation and on the sciatic nerve-gastrocnemius muscle preparation were investigated. Tobramycin, amikacin and ribostamycin produced dose-dependent neuromuscular blockade of the diaphragm twitches. Comparison of results showed that the neuromuscular blocking potency was as follows: tobramycin greater than amikacin greater than ribostamycin. The neuromuscular blockade produced gy these antibiotics was reversed by calcium chloride, whereas it was not influenced by neostigmine methylsulfate. Furthermore, the neuromuscular blocking potency in vitro of these three aminoglycosides was paralleled by their activity in vivo on the sciatic nerve-gastrocnemius muscle preparation.
