Toluene Disrupts Outer Hair Cell Morphometry and Intracellular Calcium Homeostasis in Cochlear Cells of Guinea Pigs

Liu, Ye; Fechter, Laurence D.

doi:10.1006/taap.1996.8059

Cited by 24 publications

(3 citation statements)

References 43 publications

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“…Toluene is an ototoxic organic solvent that increases free intracellular calcium levels in the spiral ganglion and the outer hair cells 16) . Although its action focuses preferently o n c o c h l e a r m i d d l e a n d m i d -a p i c a l t u r n s 1 7 ) , electrocochleographic recording of auditory evoked potentials from the round window show a hearing deficit also in the mid-low frequency region in rats, after toluene exposure 18) .…”

Section: Discussionmentioning

confidence: 99%

Toluene Alters Mu-Opioid Receptor Expression in the Rat Brainstem.

et al. 2001

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Toluene is an ototoxic organic solvent widely used in industry and could be a cause of sleep apnea. Acute toluene administration in rats induces an increase in the number of neural cells immunostained for mu-opioid receptors in several brainstem nuclei, such as the inferior colliculus, dorsal and lateral periaqueductal gray and dorsal raphe, without changes in the superior colliculus and the interpeduncular and lateral reticular nuclei. These data suggest that mu-opioid receptors could be involved in toluene-induced neurotoxic effects on the physiological regulation of breathing during sleep, and auditive function. Key words: Toluene, Mu-opioid receptors, Rat brain Materials and MethodsThe experimental animals were carefully handled and all experiments were carried out in accordance with the law, avoiding animal suffering. Toluene with purity of 99% (Analytical reagent grade, Quimon Chem. Co., Spain) was used. Toluene was diluted with olive oil at a concentration of 1 ml/ml and administered intraperitoneally to the experimental group (n=6) at a dose of 1.3 ml/kg/day for 5 consecutive days. The selected dose was 1/2 of the LD 50 per day. This dose and this kind of administration have been employed to carry out studies on the adverse effects of organic solvents 15) . The LD 50 in rats has been found in our laboratory to be 2.61 ± 0.41 ml/kg/day, calculated by the Bliss method. The control group (n=6) was given 0.9% NaCl solution in the same volume and duration as the experimental group. Two hours after the last treatment, the animals were anaesthetized with Equithensin (2 ml/kg), an alcoholic solution of nembutal and chloral hydrate (Sigma-Aldrich Química S. A.), intraperitoneally and perfused transcardially under deep anaesthesia with saline plus 50 mM phosphate buffer, pH 7.4, followed by 4% paraformaldehyde (Sigma-Aldrich Química S. A.). The brains were removed, cut into smaller pieces and then immersed in the same fixative medium overnight. They were stored for 2 days in 0.1 M phosphate buffer containing

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Section: Discussionmentioning

confidence: 99%

Toluene Alters Mu-Opioid Receptor Expression in the Rat Brainstem.

et al. 2001

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“…While this auditory impairment was recorded in laboratory animals at high toluene exposures as compared to permissible exposure levels (205), Liu and Fechter (206) demonstrated that the toxic effect in cochlear cells can be observed in vitro at toluene concentrations that are more realistic for human occupational exposure. Finally, effects on the thyroid gland (mild reduction of follide size) have been reported after toluene inhalation in female rats (207).…”

Section: Alkylbenzenes: Toluene and Xylenementioning

confidence: 93%

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

Caprino¹,

Togna²

1998

Environmental Health Perspectives

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We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and induded both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture ofthe results of toxicological studies performed in laboratory animals (induding carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics ofthe different gasoline mixtures, and from the difficulties of correcdy handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preeisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the condusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxidty in nonscientific papers and in mass-media messages.

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“…In response to sound stimulation, Ca 2+ influx and Ca 2+ -induced Ca 2+ release (CICR) from the endoplasmic reticulum significantly increase intracellular Ca 2+ in cochlear sensory cells. Factors that cause hearing impairment, such as ototoxic drugs, acoustic overstimulation, and aging, are associated with dysregulation of Ca 2+ homeostasis (Fridberger & Ulfendahl, 1996; Kidd Iii & Bao, 2012; Liu & Fechter, 1997; Richard et al, 2023). Two types of specialized sensory cells in the mammalian cochlea, inner hair cells (IHCs) and outer hair cells (OHCs), are involved in the transduction of sound into electrical responses (Dallos, 1992).…”

Section: Introductionmentioning

confidence: 99%

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

Yang,

Jeng,

Murtha

et al. 2024

Preprint

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Tight regulation of Ca2+is crucial for the function of cochlear outer hair cells (OHCs). Dysregulation of Ca2+homeostasis in OHCs is associated with impaired hearing function and contributes to increased vulnerability to environmental insults, such as noise exposure. Ca2+signaling in developing OHCs can be modulated by oncomodulin (OCM), an EF-hand calcium-binding protein. Here, we investigated whether the lack of OCM disrupts the control of intracellular Ca2+in mature OHCs, and influences vulnerability to noise. Using young adult CBA/CaJ mice, we found that OHCs fromOcm-knockout (Ocm-/-) mice exhibited normal biophysical profiles and electromotile responses compared to littermate control OHCs. Moderate noise exposure (95 dB SPL, 2 hrs) caused temporary hearing threshold shifts inOcm+/+andOcm-/-mice but the loss of hearing was permanent forOcm-/-mice. However, whileOcm+/+fully recovered their hearing 2 weeks after noise exposure,Ocm-/-mice showed permanent threshold shifts. Using a genetically encoded Ca2+sensor (GCaMP6s) expressed inOcm+/+andOcm-/-OHCs, we found that chronic noise exposure (95 dB SPL, 9 hrs) increased ATP-induced Ca2+signaling inOcm-/-OHCs compared toOcm+/+OHCs. Chronic noise exposures also caused higher hearing threshold shifts inOcm-/-mice. Prior to noise exposure, P2X2 expression was already upregulated inOcm-/-mice compared toOcm+/+mice. Following chronic noise, P2X2 receptors were upregulated in theOcm+/+cochlea but not in theOcm-/-cochlea, which retains their pre-noise high expression level. We propose that the lack of OCM increases susceptibility to noise. Increased purinergic signaling and dysregulation of cytosolic Ca2+homeostasis could contribute to early onset hearing loss in theOcm-/-mice.

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Toluene Disrupts Outer Hair Cell Morphometry and Intracellular Calcium Homeostasis in Cochlear Cells of Guinea Pigs

Cited by 24 publications

References 43 publications

Toluene Alters Mu-Opioid Receptor Expression in the Rat Brainstem.

Toluene Alters Mu-Opioid Receptor Expression in the Rat Brainstem.

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

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