Protective effect of melatonin against gentamicin ototoxicity

Lf, Ye; Zz, Tao; Qq, Hua; Bk, Xiao; Xh, Zhou; Li, Jian; Yl, Yuan

doi:10.1017/s002221510800385x

Cited by 26 publications

(26 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment of rats with MLT protected against GM‐induced ototoxicity as shown by the auditory function results and by the histological assays of HCs present in the cytocochleograms. These findings are in accord with Ye et al . (2009), who observed that MLT attenuated HC loss caused by exposure of guinea pigs to an ototoxic level of gentamicin.…”

Section: Discussionsupporting

confidence: 93%

“…Treatment of rats with MLT protected against GM-induced ototoxicity as shown by the auditory function results and by the histological assays of HCs present in the cytocochleograms. These findings are in accord with Ye et al (2009), who observed that MLT attenuated HC loss caused by exposure of guinea pigs to an ototoxic level of gentamicin. MLT has previously been demonstrated to have both antiinflammatory and neuroprotective properties by reducing IL-1b and TNF-a levels and by inhibiting the phosphorylation of p38, JNK and ERK1/2 in a spinal cord injury model (SCI; Esposito et al, 2009).…”

Section: Mlt Treatmentsupporting

confidence: 91%

See 1 more Smart Citation

Efficacy of three drugs for protecting against gentamicin‐induced hair cell and hearing losses

Bas

Water

Gupta

et al. 2012

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE Exposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM)-treated animals and cultures. EXPERIMENTAL APPROACH Wistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro-inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats. KEY RESULTS DXM, MLT and TCR decreased levels of reactive oxygen species in GM-exposed explants. The mRNA levels of TNF-α, IL-1β and TNF-receptor type 1 were significantly reduced in GM + DXM and GM + MLT groups. Phospho-p38 MAPK levels decreased in GM + MLT and GM + TCR groups, while JNK phosphorylation was reduced in GM + DXM and GM + MLT groups. Caspase-3 activation decreased in GM + DXM, GM + MLT and GM + TCR groups. These results were consistent with in vivo results. Local treatment of GM-exposed rat cochleae with either DXM, MLT or TCR preserved auditory function and prevented auditory hair cell loss. CONCLUSIONS AND IMPLICATIONS In organ of Corti explants, GM increased oxidative stress and initiated an inflammatory response that led to the activation of MAPKs and apoptosis of hair cells. The three compounds tested demonstrated otoprotective properties that could be beneficial in the treatment of ototoxicity-induced hearing loss.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Mlt Treatmentsupporting

confidence: 91%

Efficacy of three drugs for protecting against gentamicin‐induced hair cell and hearing losses

Bas

Water

Gupta

et al. 2012

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…This latter complex plays a key role in recognizing intracellular electrophils and also natural phenolics and antioxidant vitamins, thus responding to redox perturbations through the expression of genes that are under the control of the nuclear antioxidant responsive element (121). The broad spectrum of metabolic genes regulated by this signaling with a role in cell protection might contribute to explaining how melatonin prevents the cytotoxic effects of drugs such as gentamicin that was used as a factor to induce ototoxicity in guinea pigs (158) and xenobiotics with neurotoxic and prooxidant activity (159) and testicular toxicity (160).…”

Section: Melatonin Metabolism and Cell Protectionmentioning

confidence: 99%

Melatonin signaling and cell protection function

et al. 2010

View full text Add to dashboard Cite

Besides its well-known regulatory role on circadian rhythm, the pineal gland hormone melatonin has other biological functions and a distinct metabolism in various cell types and peripheral tissues. In different tissues and organs, melatonin has been described to act as a paracrine and also as an intracrine and autocrine agent with overall homeostatic functions and pleiotropic effects that include cell protection and prosurvival factor. These latter effects, documented in a number of in vitro and in vivo studies, are sustained through both receptor-dependent and -independent mechanisms that control detoxification and stress response genes, thus conferring protection against a number of xenobiotics and endobiotics produced by acute and chronic noxious stimuli. Redox-sensitive components are included in the cell protection signaling of melatonin and in the resulting transcriptional response that involves the control of NF-κB, AP-1, and Nrf2. By these pathways, melatonin stimulates the expression of antioxidant and detoxification genes, acting in turn as a glutathione system enhancer. A further and converging mechanism of cell protection by this indoleamine described in different models seems to lie in the control of damage and signaling function of mitochondria that involves decreased production of reactive oxygen species and activation of the antiapoptotic and redox-sensitive element Bcl2. Recent evidence suggests that upstream components in this mitochondrial route include the calmodulin pathway with its central role in melatonin signaling and the survival-promoting component of MAPKs, ERK1/2. In this review article, we will discuss these and other molecular aspects of melatonin signaling relevant to cell protection and survival mechanisms.

show abstract

“…Melatonin was put forward as a potent free radical scavenger and an antiapoptotic agent in utricular hair cells . The studies observed that melatonin attenuated hairy cell loss caused by exposure to an ototoxic level of gentamicin …”

Section: Discussionmentioning

confidence: 99%

“…34 The studies observed that melatonin attenuated hairy cell loss caused by exposure to an ototoxic level of gentamicin. 35,36…”

Section: Discussionmentioning

confidence: 99%