Soya Rungsung1, Thakur Uttam Singh2, Kirthika Perumalraja3, Archana Mahobiya1, Meemansha Sharma1, Madhu Cholenahalli Lingaraju1, Subhashree Parida1, Monalisa Sahoo4, Dinesh Kumar1. 1. Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. 2. Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. tusingh80@gmail.com. 3. Division of Animal Biochemistry, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. 4. Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India.
Abstract
BACKGROUND: Luteolin, a naturally occurring flavonoid, is thought to have health-promoting properties as a part of human diet and has been reported to possess a wide range of pharmacological activities. Therefore, the present study was undertaken to evaluate the effect of luteolin pre-treatment on vascular dysfunctions in sepsis induced by caecal ligation and puncture (CLP) in the mouse model. METHODS: Mice were divided into four groups: sham, luteolin plus sham, CLP, and luteolin plus CLP. Luteolin was administered (0.2 mg/kg body weight) intraperitoneally one hour (h) before CLP surgery in mice. 20 ± 2 h post CLP surgery, the isolated thoracic aorta of mice was assessed for its vascular reactivity to noradrenaline (NA) and acetylcholine (ACh). To explore the underlying mechanism, aortic mRNA expressions of α1D adrenoceptors, eNOS and iNOS were investigated. RESULTS: In mice with CLP-induced sepsis luteolin pre-treatment markedly increased the survival time and attenuated serum lactate level. The CLP group manifested the reduced vascular reactivity to NA and this deficit was restored by luteolin pre-treatment. However, luteolin pre-treatment did not improve α1D adrenoceptors down-regulation observed in septic mice aorta. In the presence of 1400 W, the NA contractile response was significantly restored in CLP mice aortic tissue in comparison with the respective control of septic mice and further enhanced in the presence of luteolin. Luteolin reduced the iNOS mRNA expression and iNOS-derived nitrite production. Pre-treatment with luteolin restored the endothelial dysfunction in septic mice aorta by improving eNOS mRNA expression and enhanced eNOS-derived nitric oxide (NO) production in septic mice aorta and aortic iNOS gene expression and inducible NO production. CONCLUSION: The present study suggests that the vasoplegic state to NA in aorta was restored through the iNOS pathway and endothelial dysfunction was reversed via eNOS and NO production pathway.
BACKGROUND: Luteolin, a naturally occurring flavonoid, is thought to have health-promoting properties as a part of human diet and has been reported to possess a wide range of pharmacological activities. Therefore, the present study was undertaken to evaluate the effect of luteolin pre-treatment on vascular dysfunctions in sepsis induced by caecal ligation and puncture (CLP) in the mouse model. METHODS: Mice were divided into four groups: sham, luteolin plus sham, CLP, and luteolin plus CLP. Luteolin was administered (0.2 mg/kg body weight) intraperitoneally one hour (h) before CLP surgery in mice. 20 ± 2 h post CLP surgery, the isolated thoracic aorta of mice was assessed for its vascular reactivity to noradrenaline (NA) and acetylcholine (ACh). To explore the underlying mechanism, aortic mRNA expressions of α1D adrenoceptors, eNOS and iNOS were investigated. RESULTS: In mice with CLP-induced sepsis luteolin pre-treatment markedly increased the survival time and attenuated serum lactate level. The CLP group manifested the reduced vascular reactivity to NA and this deficit was restored by luteolin pre-treatment. However, luteolin pre-treatment did not improve α1D adrenoceptors down-regulation observed in septic mice aorta. In the presence of 1400 W, the NA contractile response was significantly restored in CLP mice aortic tissue in comparison with the respective control of septic mice and further enhanced in the presence of luteolin. Luteolin reduced the iNOS mRNA expression and iNOS-derived nitrite production. Pre-treatment with luteolin restored the endothelial dysfunction in septic mice aorta by improving eNOS mRNA expression and enhanced eNOS-derived nitric oxide (NO) production in septic mice aorta and aortic iNOS gene expression and inducible NO production. CONCLUSION: The present study suggests that the vasoplegic state to NA in aorta was restored through the iNOS pathway and endothelial dysfunction was reversed via eNOS and NO production pathway.
Authors: Ari Moskowitz; Yasser Omar; Maureen Chase; Sharukh Lokhandwala; Parth Patel; Lars W Andersen; Michael N Cocchi; Michael W Donnino Journal: J Crit Care Date: 2016-12-02 Impact factor: 3.425
Authors: Amanda Ruth; Courtney E McCracken; James D Fortenberry; Matthew Hall; Harold K Simon; Kiran B Hebbar Journal: Pediatr Crit Care Med Date: 2014-11 Impact factor: 3.624
Authors: Jianhui Sun; Huacai Zhang; Di Liu; Li Cui; Qiang Wang; Lebin Gan; Dalin Wen; Jun Wang; Juan Du; Hong Huang; Anqiang Zhang; Jin Deng; Jianxin Jiang; Ling Zeng Journal: Front Genet Date: 2021-09-03 Impact factor: 4.599