Angiotensin II receptor blocker irbesartan attenuates sleep apnea-induced cardiac apoptosis and enhances cardiac survival and Sirtuin 1 upregulation.
3区 · 医学
作者: Pei-Ying Pai ; Yi-Yuan Lin ; Shao-Hong Yu ; Ching-Yuang Lin ; Yi-Fan Liou ; Xu-Bo Wu ; James K S Wong ; Chih-Yang Huang ; Shin-Da Lee
The purpose of this study was to investigate whether or not angiotensin II type 1 receptor blocker irbesartan (ARB) with a partial agonist of PPAR-γ could protect against chronic nocturnal intermittent hypoxia (CIH)-induced cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis.
Sprague-Dawley rats were in a normoxic control group (CON-G), or rats were in a chronic nocturnal intermittent hypoxia group (HP-G, from 3 to 7% oxygen versus 21% oxygen per forty seconds cycle, nocturnally 8 h per day for 1 month), or rats were in a chronic nocturnal intermittent hypoxia group pretreated with ARB (50 mg/kg/day, S.C.) (ARB-HP-G). Echocardiography, H&E staining, TUNEL staining, and Western blotting were measured in the left ventricle.
Hypoxia-induced SIRT1 degradation, Fas receptors, FADD, active caspase-8 and caspase-3 (Fas/FasL apoptotic pathway) and Bax, tBid, active caspase-9 and -3 (mitochondrial apoptotic pathway) and TUNEL-positive apoptosis were reduced in ARB-HP-G when compared with HP-G. IGF-I, IGF1 receptor, p-PI3k, p-Akt, Bcl2, and Bcl-XL (IGF1/PI3K/AKT pro-survival pathway) were increased in ARB-HP-G compared to HP-G.
Our findings suggest that the ARB may prevent cardiac Fas/FasL to mitochondrial apoptotic pathways and enhance cardiac IGF1/PI3K/AKT pro-survival pathway in the sleep apnea model associated with JNK de-activation and SIRT1 upregulation. ARB prevents chronic sleep apnea-enhanced cardiac apoptosis via enhancing survival pathways.
2017-06-01·International journal of pediatric otorhinolaryngology3区 · 医学
Protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss.
3区 · 医学
作者: Deniz Tuna Edizer ; Ozgur Yigit ; Zehra Cinar ; Mehmet Gul ; Eyyup Kara ; Birgul Yigitcan ; Duygu Hayır ; Ahmet Atas
Aminoglycosides, used to combat with life-threatening infections, have a substantial risk of hearing loss. Nigella sativa is an annual herbaceous plant and used for treatment of many diseases for ages. We aimed to investigate the protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss in an animal model.
METHODS AND MATERIALS:
Twenty eight guinea pigs were randomly divided into four groups: i-control, ii- Intratympanic nigella sativa oil (IT-NSO), iii- Intraperitoneal gentamicin (IP-G) and iv- Intraperitoneal gentamicin and intratympanic nigella sativa oil (IP-G + IT-NSO). Preoperative and postoperative hearing thresholds were determined with auditory brainstem response with click and 8 kHz tone-burst stimuli. Histological analysis of the cochlea specimens were performed under light microscope. Semiquantitative grading of the histological findings was carried out and compared between the groups.
Highest posttreatment hearing thresholds were detected in IP-G group. Posttreatment mean hearing threshold of the IP-G group with click stimulus was significantly higher than the IP-G + IT-NSO group (p = 0.004). whereas the difference was not significant with 8 kHz tone-burst stimulus (p = 0.137). Both IP-G and IP-G + IT-NSO groups had significantly higher hearing thresholds compared to control and IT-NSO groups (p > 0.05). Histological examination of the control and IT-NSO groups demonstrated normal appearance of cochlear nerve, stria vascularis and organ of Corti. IP-G group showed the most severe histological alterations including hydropic and vacuolar degenerations, hair cell damage and deformation of the basilar mambrane. Histological evidence of damage was significantly reduced in IP-G + IT-NSO group compared to IP-G group.
Addition of intratympanic NSO to systemic gentamicin was demonstrated to have beneficial effects in hearing thresholds which was supported by histological findings.