scholarly journals Telmisartan Attenuates Kanamycin-Induced Ototoxicity in Rats

2021 ◽  
Vol 22 (23) ◽  
pp. 12716
Author(s):  
Chang Ho Lee ◽  
So Min Lee ◽  
So Young Kim

Telmisartan (TM) has been proposed to relieve inflammatory responses by modulating peroxisome proliferator activator receptor-γ (PPARγ) signaling. This study aimed to investigate the protective effects of TM on kanamycin(KM)-induced ototoxicity in rats. Forty-eight, 8-week-old female Sprague Dawley rats were divided into four groups: (1) control group, (2) TM group, (3) KM group, and (4) TM + KM group. Auditory brainstem response was measured. The histology of the cochlea was examined. The protein expression levels of angiotensin-converting enzyme 2 (ACE2), HO1, and PPARγ were measured by Western blotting. The auditory threshold shifts at 4, 8, 16, and 32 kHz were lower in the TM + KM group than in the KM group (all p < 0.05). The loss of cochlear outer hair cells and spiral ganglial cells was lower in the TM + KM group than in the KM group. The protein expression levels of ACE2, PPARγ, and HO1 were higher in the KM group than in the control group (all p < 0.05). The TM + KM group showed lower expression levels of PPARγ and HO1 than the KM group.TM protected the cochlea from KM-induced injuries in rats. TM preserved hearing levels and attenuated the increase in PPARγ and HO1 expression levels in KM-exposed rat cochleae.

2020 ◽  
Vol 21 (10) ◽  
pp. 3503 ◽  
Author(s):  
Chang Ho Lee ◽  
Da-hye Lee ◽  
So Min Lee ◽  
So Young Kim

Previous studies have described the effects of zingerone (ZO) on cisplatin (CXP)-induced injury to the kidneys, liver, and other organs but not to the cochlea. This study aimed to investigate the effects of ZO on CXP-induced ototoxicity. Eight-week-old Sprague–Dawley rats were used and divided into a control group, a CXP group, and a CXP + ZO group. Rats in the CXP group received 5 mg/kg/day CXP intraperitoneally for five days. Rats in the CXP + ZO group received 5 mg/kg/day CXP intraperitoneally for five days and 50 mg/kg/day ZO intraperitoneally for seven days. Auditory brainstem response thresholds (ABRTs) were measured before (day 0) and after (day 10) drug administration. Cochlear histology was examined using hematoxylin and eosin (H&E) staining and cochlear whole mounts. The expression levels of cytochrome P450 (CYP)1A1, CYP1B1, inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), and interleukin 6 (IL6) were estimated using quantitative reverse transcription-polymerase chain reaction. The expression levels of heme oxygenase 1 (HO1) and caspase 3 were analyzed via Western blotting. The auditory thresholds at 4, 8, and 16 kHz were attenuated in the CXP + ZO group compared with the CXP group. The mRNA expression levels of CYP1A1, CYP1B1, iNOS, NFκB, TNFα, and IL6 were lower in the CXP + ZO group than in the CXP group. The protein expression levels of HO1 and caspase 3 were lower in the CXP + ZO group than in the CXP group. Cotreatment with ZO exerted otoprotective effects against CXP-induced cochlear injury via antioxidative and anti-inflammatory activities involving CYPs, iNOS, NFκB, and TNFα.


2021 ◽  
pp. 1-13
Author(s):  
Selis Gulseven Guven ◽  
Onur Ersoy ◽  
Ruhan Deniz Topuz ◽  
Erdoğan Bulut ◽  
Gulnur Kizilay ◽  
...  

<b><i>Introduction:</i></b> The effect of orally consumed monosodium glutamate (MSG), which is a common additive in the food industry, on the cochlea has not been investigated. The present study aimed to investigate the possible cochleotoxic effects of oral MSG in guinea pigs using electrophysiological, biochemical, and histopathological methods. <b><i>Methods:</i></b> Thirty guinea pigs were equally divided into control and intervention groups (MSG 100 mg/kg/day; MSG 300 mg/kg/day). At 1 month, 5 guinea pigs from each group were sacrificed; the rest were observed for another month. Electrophysiological measurements (distortion product otoacoustic emission [DPOAE] and auditory brainstem response [ABR]), glutamate levels in the perilymph and blood samples, and histopathological examinations were evaluated at 1 and 2 months. <b><i>Results:</i></b> Change in signal-to-noise ratio at 2 months was significantly different in the MSG 300 group at 0.75 kHz and 2 kHz (<i>p</i> = 0.013 and <i>p</i> = 0.044, respectively). There was no statistically significant difference in ABR wave latencies of the guinea pigs given MSG compared to the control group after 1 and 2 months; an increase was noted in ABR thresholds, although the difference was not statistically significant. In the MSG groups, moderate-to-severe degeneration and cell loss in outer hair cells, support cells, and spiral ganglia, lateral surface junction irregularities, adhesions in stereocilia, and partial loss of outer hair cell stereocilia were noted. <b><i>Conclusion:</i></b> MSG, administered in guinea pigs at a commonly utilized quantity and route of administration in humans, may be cochleotoxic.


2014 ◽  
Vol 128 (4) ◽  
pp. 331-335 ◽  
Author(s):  
S J Daniel ◽  
M McIntosh ◽  
O V Akinpelu ◽  
C V Rohlicek

AbstractObjective:To determine the effect of experimentally induced hypoxia, in the first 10 days of life, on physiological hearing in a Sprague–Dawley rat model.Methods:A prospective, controlled animal study was carried out using 22 male rat pups. The rats in the hypoxic group (n = 12) were reared in hypoxia for the first 10 days of life, and subsequently reared in normoxia, while those in the control group (n = 10) were reared in normoxia for the duration of the experiment. Hearing was assessed using auditory brainstem response testing at approximately 72 days of age.Results:The hypoxia group had higher auditory brainstem response thresholds for all frequencies tested (more pronounced at 16 kHz), compared with controls. Wave I–V inter-peak latencies were more prolonged in the hypoxic rats, while both groups had similar wave I latencies.Conclusion:Chronic postnatal hypoxia induced permanent hearing loss in this Sprague–Dawley rat model. Prolonged wave I–V inter-peak latencies suggested functional abnormality in the central auditory pathway.


2021 ◽  
Vol 19 ◽  
Author(s):  
Anni Du ◽  
Rui Cai ◽  
Jingshan Shi ◽  
Qin Wu

Background: Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Icariin (ICA) is a flavonoid derived from the genus Epimedium which is a traditional Chinese herb, a potential therapeutic drug for TBI. This study aims to explore the protective effect of ICA on TBI and its mechanism Methods: Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received ICA (15 mg/kg, 30 mg/kg and 60 mg/kg), while the sham group was gavaged with equal volumes of saline. The beam-balance testing and prehensile traction test were used for neurological scoring. Pathological changes were observed by H&E staining. The protein expression levels of inflammatory factors were measured by Western blot analysis Results: It was found that ICA significantly improved the neuroethology function and alleviated the pathological injury in TBI rats. The protein expression levels of inflammatory factors COX-2, IL-1β, and TNF-α and its regulatory proteins p-NF-κB-p65, p-ERK1/2, p-JNK, and p-p38 were increased in the cerebral cortex injured by TBI. The protein expression levels of inflammatory cytokines were markedly decreased in cerebral cortex of TBI rats when administrated with ICA. Conclusion: The present study demonstrates that ICA may be a promising therapeutic strategy for reducing inflammation in TBI.


2003 ◽  
Vol 14 (03) ◽  
pp. 124-133 ◽  
Author(s):  
Kathleen C.M. Campbell ◽  
Deb L. Larsen ◽  
Robert P. Meech ◽  
Leonard P. Rybak ◽  
Larry F. Hughes

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine. El glutatión (GSH) brinda una importante vía antioxidante y de cetoxificación. Realizamos una prueba para determinar si la administración directa de GSH o del éster de GSH podía reducir la ototoxicidad inducida por cisplatino (CDDP). Hicimos una evaluación en ocho grupos de cinco ratas cada uno: un grupo control, un grupo que recibió CDDP intraperitoneal a 16 mg/kg en una ínfusión durante 30 minutos y seis grupos que recibieron intraperitonealmente GSH o el éster de GSH a 500, 1000 o 1500 mg/kg, 30 minutos antes del CDDP a 16 mg/kg. Se midieron umbrales de respuestas auditivas del tallo cerebral tanto para clicks como para bursts tonales, al inicio y 3 días después. La pérdida de células ciliadas externas (OHC) fue establecida a nivel de las vueltas apical, media y basal. La dosis de 500 mg/kg de éster de GSH redujo la hipoacusia y la pérdida de OHC, pero la protección disminuyó conforme la dosis se incrementó, sugiriendo una posible toxicidad. EL GSH no resultó significativamente protector. El mejor efecto protector del éster de GSH fue menor que el previamente reportado con D-Metionina.


2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.


2003 ◽  
Vol 14 (03) ◽  
pp. 134-143 ◽  
Author(s):  
James J. Klemens ◽  
Robert P. Meech ◽  
Larry F. Hughes ◽  
Satu Somani ◽  
Kathleen C.M. Campbell

This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of aminoglycoside (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 ≤ 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. 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.


Author(s):  
Ryuni Kim ◽  
Hyebeen Kim ◽  
Minju Im ◽  
Sun Kyu Park ◽  
Hae Jung Han ◽  
...  

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.


2020 ◽  
Vol 19 (2) ◽  
pp. 296-303
Author(s):  
Eni Widayati ◽  
Taufiqurrachman Nasihun ◽  
Azizah Hikma Savitri ◽  
Nurina Tyagita

Objective: The effect of Pimpinela alpina Molk (PaM) on decrease in Bax and Caspase-3 protein expression in liver cells apoptosis have been proven. However, the difference result between 7 and 15 days treatment duration of PaM need to be confirmed. This study aimed to confirm that treatment of PaM during 15 days is more effective decreasing Bax and Caspase-3 protein expression in liver cells following UVB irradiation. Methods: In the post test only control group design, 35 Sprague Dawley male rats, 300 gram body weight were divided into two arms, consisting of three groups respectively. First arm comprise Neg-7, PaM7-100, and PaM7-150. Second arm comprise Neg-15, PaM15-100, and PaM15-150. Nor-G was added as normal control neither exposed to UVB nor PaM treatment. In negative group was only radiated to UVB and PaM groups were exposed to UVB and treatment with 100, and 150 mg PaM per oral for 7 and 15 days respectively. At day 8 (first arm) and 16 (second arm), liver organ was taken and Bax and Caspase-3 protein expression assessed by Immunohistochemical staining method. Result: Post Hoc LSD analysis indicated that Bax and Caspase-3 protein expression in PaM15-100 and PaM15-150 was significant lower compared to that of Nor-G, PaM7-100, and PaM7-150, p < 0.05. Conclusion: Ttreatment of PaM with doses 100 and 150 mg for 15 days was better in decreasing Bax and Caspase-3 protein expression of liver cells following UVB irradiation. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.296-303


2020 ◽  
Vol 23 (4) ◽  
pp. 570-579
Author(s):  
Mahboubeh Sheikhan ◽  
◽  
Mohammad Reza Kordi ◽  
Hamid Rajabi ◽  
◽  
...  

Background and Aim: Several microRNAs are involved in regulating muscle mass, which plays an essential role in hypertrophy and atrophy of skeletal muscle, The present study examined the expression of some genes as regulators of muscular atrophy following a period of inertia in rats. Methods & Materials: For this purpose, 18 male Sprague-Dawley rats were divided into three groups (Control, Exercise+inactivity, and Inactivity). The exercise+inactivity group run on the treadmill for 18 weeks and five times per week. The hindlimb of the animal was immobilized for seven days with the casting method. Soleus muscle was extracted and the expression of the genes was measured by the RT-PCR method. Univariate ANOVA and Tukey post hoc test was used to determine the differences (α=0.05). Ethical Considerations: The Ethics Committee of the Tehran University of Medical Sciences Research approved this study (Code: IR.SUMS.REC.1396.S 463). Results: Results showed that immobilization in both Exercise+ inactivity and inactivity groups, compare to the control group, increased expression of miR-1 genes (P<0.10), FOXO3a (P<0.001) and decreased expression of miR-206 (P<0.007) and IGF-1 (P<0.001). This difference was statistically significant. Conclusion: According to the results of this study, it can be said that changes in the expression of RNAs by chromatography cause changes in the expression of muscle regulating genes, and although endurance exercises have protective effects, they cannot prevent these changes.


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