Hi I just posted this on another thread, but I believe it is important enough to have its own thread....if I do say so myself. It is very late so hopefully this will make sense...I will check in the morning and make sure.!!!
I have been seeing a lot of people talking about hearing loss and Tobra, amikacin and other aminoglycosides...(gent) I have been doing a lot of research on this topic and I just wanted to post some of the info.
Basically, what it comes down to is this. Hearing loss, is due to oxidative stress...even hearing loss due to aging is due to to a decrease in antioxidants. Injury from load noise is a product of oxidative stress and can be prevented with antioxidant supplementation. As cfers, we are critically low in many of these antioxidants...when subjected to repeated rounds of oto-toxic drugs, our oxidative burdens are sometimes too much and we experience hearing loss. I had terrible ringing four years ago when taking amikacin and tobra..we tried several times and had to discontiue because they were worried about hearing loss. After getting started on a healthy diet, antioxidant supplemention, magnesium and probiotics..I am able to take these drugs with no problem now. The ringing has never recurred and I am a firm believer this had to due with my change in antioxidant status...
As I have stated so many times..I know, I never shut up, my vit, mineral and antioxidant levels have all improved so much from four years ago when I had them all tested...Anyway, just wanted you guys to read some studies from PIER REVIEWD JOURNALS. If you are having a problem with these drugs, you really should consider arming yourself with this knowledge!!!!
I demanded to have all of these antioxidants tested in my blood because I knew what they did not have time to learn....antioxidants matter, glutathione matters, vit e matters, vit c matters. If you are unsure about taking supplements, go have you blood tested...
I saw somewhere that hearing loss is the nature of the beast (of aminoglicosides.) Well put, but unfortunately, very incomplete....We can protect ourselves and we should demand it. Interestingly, when you pub-med search aminoglycosides and antioxidants tons of stuff comes up.....if you add cf, hearing loss, antioxidants aminoglycosides nothing..... we have got to wake some people up <img src="i/expressions/face-icon-small-smile.gif" border="0">
<b>Antioxidant enzyme levels inversely covary with hearing loss after amikacin treatment. </b>
Klemens JJ,
Meech RP,
Hughes LF,
Somani S,
Campbell KC.
Southern Illinois University School of Medicine, Springfield, IL, USA.
This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of amino-glycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p < or = 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds.<b> The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary.
</b>PMID: 12859138 [PubMed - indexed for MEDLINE]
<b>The role of antioxidants in protection from ototoxic drugs.</b>
Sergi B,
Fetoni AR,
Ferraresi A,
Troiani D,
Azzena GB,
Paludetti G,
Maurizi M.
Institute of Otolaryngology, Catholic University of Rome, Italy. carosergi@yahoo.com
A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. <b>In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.
PMID: 15219046
</b>
1: Hear Res. 1995 Jun;86(1-2):15-24. Links
<b>Glutathione protection against gentamicin ototoxicity depends on nutritional status</b>.
Lautermann J,
McLaren J,
Schacht J.
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
This study demonstrates that gentamicin ototoxicity depends on dietary factors and correlates with tissue glutathione levels. After 15 days of gentamicin injections (100 mg/kg/day s.c.) guinea pigs on a regular protein diet (18.5% protein) had an average hearing loss of 9 dB at 3 kHz, 31 dB at 8 kHz and 42 dB at 18 kHz. Guinea pigs on a 7% protein diet showed an increased hearing loss of 52 dB at 3 kHz, 63 dB at 8 kHz and 74 dB at 18 kHz. Supplementing the low protein diet with either essential or sulfur-containing amino acids did not protect against gentamicin ototoxicity. Glutathione levels in the cochlear sensory epithelium were decreased in animals on a low protein diet and could be restored to normal by oral administration of glutathione monoethyl ester (1.2 g/kg/day) in combination with vitamin C (100 mg/kg/day). Glutathione supplementation significantly reduced the magnitude of hearing loss in the low protein diet group at all frequencies (43 dB reduction at 3 kHz, 27 dB reduction at 8 kHz and 21 dB reduction at 18 kHz). In animals on a full protein diet, dietary glutathione neither increased cochlear glutathione levels nor attenuated hearing loss. Serum gentamicin levels did not differ between animals on the various diets with or without glutathione supplement. <b>These results suggest that gentamicin toxicity and detoxifying mechanisms are affected by the metabolic state of the animal and the glutathione content of the tissue. Thus, compounds that could potentially protect against gentamicin ototoxicity may be more correctly assessed in animal models of deficient nutritional states in which endogenous detoxifying mechanisms are compromised. This animal model might also be more realistically related to the clinical situation of a critically ill patient receiving gentamicin treatment. </b>
<b>Glutathione limits noise-induced hearing loss</b>.
Ohinata Y,
Yamasoba T,
Schacht J,
Miller JM.
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109-0506, USA.
The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. <b>These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention. </b>
I have been seeing a lot of people talking about hearing loss and Tobra, amikacin and other aminoglycosides...(gent) I have been doing a lot of research on this topic and I just wanted to post some of the info.
Basically, what it comes down to is this. Hearing loss, is due to oxidative stress...even hearing loss due to aging is due to to a decrease in antioxidants. Injury from load noise is a product of oxidative stress and can be prevented with antioxidant supplementation. As cfers, we are critically low in many of these antioxidants...when subjected to repeated rounds of oto-toxic drugs, our oxidative burdens are sometimes too much and we experience hearing loss. I had terrible ringing four years ago when taking amikacin and tobra..we tried several times and had to discontiue because they were worried about hearing loss. After getting started on a healthy diet, antioxidant supplemention, magnesium and probiotics..I am able to take these drugs with no problem now. The ringing has never recurred and I am a firm believer this had to due with my change in antioxidant status...
As I have stated so many times..I know, I never shut up, my vit, mineral and antioxidant levels have all improved so much from four years ago when I had them all tested...Anyway, just wanted you guys to read some studies from PIER REVIEWD JOURNALS. If you are having a problem with these drugs, you really should consider arming yourself with this knowledge!!!!
I demanded to have all of these antioxidants tested in my blood because I knew what they did not have time to learn....antioxidants matter, glutathione matters, vit e matters, vit c matters. If you are unsure about taking supplements, go have you blood tested...
I saw somewhere that hearing loss is the nature of the beast (of aminoglicosides.) Well put, but unfortunately, very incomplete....We can protect ourselves and we should demand it. Interestingly, when you pub-med search aminoglycosides and antioxidants tons of stuff comes up.....if you add cf, hearing loss, antioxidants aminoglycosides nothing..... we have got to wake some people up <img src="i/expressions/face-icon-small-smile.gif" border="0">
<b>Antioxidant enzyme levels inversely covary with hearing loss after amikacin treatment. </b>
Klemens JJ,
Meech RP,
Hughes LF,
Somani S,
Campbell KC.
Southern Illinois University School of Medicine, Springfield, IL, USA.
This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of amino-glycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p < or = 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds.<b> The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary.
</b>PMID: 12859138 [PubMed - indexed for MEDLINE]
<b>The role of antioxidants in protection from ototoxic drugs.</b>
Sergi B,
Fetoni AR,
Ferraresi A,
Troiani D,
Azzena GB,
Paludetti G,
Maurizi M.
Institute of Otolaryngology, Catholic University of Rome, Italy. carosergi@yahoo.com
A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. <b>In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.
PMID: 15219046
</b>
1: Hear Res. 1995 Jun;86(1-2):15-24. Links
<b>Glutathione protection against gentamicin ototoxicity depends on nutritional status</b>.
Lautermann J,
McLaren J,
Schacht J.
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
This study demonstrates that gentamicin ototoxicity depends on dietary factors and correlates with tissue glutathione levels. After 15 days of gentamicin injections (100 mg/kg/day s.c.) guinea pigs on a regular protein diet (18.5% protein) had an average hearing loss of 9 dB at 3 kHz, 31 dB at 8 kHz and 42 dB at 18 kHz. Guinea pigs on a 7% protein diet showed an increased hearing loss of 52 dB at 3 kHz, 63 dB at 8 kHz and 74 dB at 18 kHz. Supplementing the low protein diet with either essential or sulfur-containing amino acids did not protect against gentamicin ototoxicity. Glutathione levels in the cochlear sensory epithelium were decreased in animals on a low protein diet and could be restored to normal by oral administration of glutathione monoethyl ester (1.2 g/kg/day) in combination with vitamin C (100 mg/kg/day). Glutathione supplementation significantly reduced the magnitude of hearing loss in the low protein diet group at all frequencies (43 dB reduction at 3 kHz, 27 dB reduction at 8 kHz and 21 dB reduction at 18 kHz). In animals on a full protein diet, dietary glutathione neither increased cochlear glutathione levels nor attenuated hearing loss. Serum gentamicin levels did not differ between animals on the various diets with or without glutathione supplement. <b>These results suggest that gentamicin toxicity and detoxifying mechanisms are affected by the metabolic state of the animal and the glutathione content of the tissue. Thus, compounds that could potentially protect against gentamicin ototoxicity may be more correctly assessed in animal models of deficient nutritional states in which endogenous detoxifying mechanisms are compromised. This animal model might also be more realistically related to the clinical situation of a critically ill patient receiving gentamicin treatment. </b>
<b>Glutathione limits noise-induced hearing loss</b>.
Ohinata Y,
Yamasoba T,
Schacht J,
Miller JM.
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109-0506, USA.
The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. <b>These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention. </b>