Study Of Lysisin Aspirin,Resveratrol On Their Protection Against Gentamicin Ototoxicity

Aminoglycoside antibiotics (AmAn) are effective drugs in treatment against gram-negative infections, but the ototoxicity and nephrotoxicity brought by them limit their use in clinic. In recent years, some studies demonstrated that mechanism of AmAn ototoxicity lies in the formation of AmAn-iron complex, which catalyze the production of free radicals. The latter cause a serial of impairs in cochlear tissue. However, some kinds of radical scavengers and iron chelators can prevent or attenuate aminoglycoside antibiotic induced deafness, which seems possible to diminish toxicity of AmAn and greatly expand application of AmAn. In this paper, protection effects of lysisin aspirin (LAP) and resveratrol (Res) against gentamicin (GM) ototoxicity were demonstrated and the potential mechanism was also discussed.Part one1 Lysisin aspirin protection against gentamicin ototoxicityIt comprised of 4 groups(randomly divided) of 48 male pigmented guinea pigs in which GM and LAP was injected alone or in combination, besides control group. Acoustic brainstem response(ABR) and cochlear preparation, transmission electric microscope were used to observe the changes on hearing threshold and morphology before and after the injection; to measure the concentration of MDA SOD and iron in cochlear and renal tissue as well as to find out the potential mechanism. Serum levels of GM, BUN and Cr. were also tested.Results: (1)GM group developed a progressive threshold shift reaching40~80dB at 8kHz,concurrently injection of LAP reducing threshold shift to 15~35dB(P<0.01). Hearing loss of high frequency was heavier than that of low frequency. Thresholds of control group and LAP group maintained steadily.(2)Morphological results were consistent with functional changes. The worst damages occurred in the basal circles. Damages in upper circles were lighter. (3)MDA concentration of blood serum in GM+LAP group significantly decreased while SOD levels increased on the day, compared with GM group.(4) BUN and Cr levels in GM+LAP or control group were significantly lower than those in GM group.(5) No obvious difference lied in serum GM level between the GM group and GM+LAP group.Conclusions:(l)GM increases ABR threshold of guinea pig, which can be attenuated by concurrently injection of LAP. (2)GM mainly impairs outer hair cell, on which LAP has protection effect. (3)LAP attenuates renal toxicity of GM by decreasing BUN and Cr level.(4)LAP does not affect the serum levels of GM.(5)GM may enhance peroxidase reaction in blood serum, which can be suppressed by LAP. (6) Relationship between GM toxicity and free radical is not confirmed in this study.2 Observation on the compatibility of gentamicin and lysisin aspirinThe safety of compatibility of GM and LAP was discussed through observing the mixture's color, optical rotation and sediments separately under the temperature of 25 ℃ and 37℃.Results:(1)No change in color and no sediment occurred under the temperature 25℃ and 37℃; Also no obvious difference was seen in the PH value under the two different temperatures.(2)No obvious difference of optical rotation was seen between the mixed drug and purely medical drug.Conclusions:(l)No change in color, PH value, concentration and pellucidity occurs in the mixture of GM and LAP.(2)The effect of the mixed drug is as the same as that of pre-mixture.(3)The ideal percentage of normal Saline is 0.9% when mixing LAP with GM.3 The test of ABR and observation on cochlear preparation after the injection of GM+LAPIn experiment, 20 healthy male pigmented guinea pigs were randomlydivided into two groups (each 10). The usual clinical doses were used both in GM group and GM+LAP group in order to observe the safety and effect of the mixed drug. GM group: 12mg/kg, one injection per day; GM+LAP group: GM 12mg/kg + LAP 135mg/kg, one combined injection under skin per day.Results:(l) (1)GM group developed a progressive threshold shift reaching 17~20dB at 8kHz,concurrently injection of LAP reducing threshold shift to 15~18dB(...