Role of vitamin E on intestinal and renal autophagy (Gut renal axis) in high fat - high fructose fed and endotoxemic rat models /
دور فيتامين هـ فى الالتهام الذاتى للامعاء والكلى فى نماذج من الفئران مسممة الخلايا ومغذاة بنسبة عالية من الدهون والفركتوز
Neamat Mahmoud Abdelgilil ; Supervised Magda Mahmoud Elhamzawy , Nevien Mahmoud Mustafa , Asmaa Mohammed Shams Eldeen
- Cairo : Neamat Mahmoud Abdelgilil , 2020
- 238 P. : charts , facimiles ; 25cm
Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Physiology
Background and aims: Despite the plentiful researches that have been conducted to clarify the underling pathophysiology of the effect of HFD and fructose on the intestinal homeostasis and the disturbance of this homeostasis (dysbiosis) under septic conditions yet, there are a few studies which focused on the renal affection not only by the direct effect of both HFHF diet and sepsis but also through a gut-renal axis which depends on the leakage of endotoxins together with short chain fatty acids (SCFAs) which modulate renal functions. Autophagy and ER stress are cellular events which play fundamental roles in injury to keep the intestinal and renal homeostasis under stressful conditions.Thus, the main aim of the present study was to shed the light on the potential modulatory effects which are triggered by intestinaland renal ER stress on autophagic machinery in maintaining the intestinal homeostasis in response to HFHF over-nutrition especially under septic status and the impact of these modulations via the gut-renal axis on renal functions.The second objective in the study was to investigate the impact of vitamin E supplementation on these autophagy-mediated and ER-stress related modulations. Methods: Fifty four adult male albino rats were randomly allocated into three main experimental groups in addition to the control group for comparison. Each of the main groupswas subdivided as follows; Control group:which was subdivided into three subgroups ( control-diet , control-vehicle and control-drug i.e. vitamin E), High fat-high fructose (HFHF) fed groupwhich was subdivided into subgroups HFHF-V (vehicle-treated) and HFHF-E (Vitamin E-treated), septic group (LPS) which was subdivided into subgroups LPS-V (vehicle-treated) and LPS-E i.e. Vitamin E-treated and lastly combined group (HFHF+LPS)which was also subdivided into subgroups HFHF+LPS-V (vehicle-treated) and HFHF+LPS-E i.e. Vitamin E-treated).At the end of the experimental protocol, serum LPS and SCFAs, intestinal integrity markers (Occludin and ZO-1), renal functions (urea, creatinine, BUN and serum NGAL)and protein and gene expression of the inflammatory markers TLR4 , NF-kB were estimated.Autophagy and ER stress parameters (mTOR, Beclin, LC3) and (CHOP,XBP1, ATF4 and ATF6)respectively were also assessed in intestinal and renal tissues. In addition, the jejunal and renal architectures were assessed histologically