Implication of endoplasmic reticulum stress and mitochondrial perturbations in remote liver injury after renal ischemia/reperfusion in rats: potential protective role of azilsartan
Rania A. Elrashidy,
Esraa M. Zakaria,
Rehab A. Hasan,
Asmaa M. Elmaghraby,
Dina A. Hassan,
Ranya M. Abdelgalil,
Shaimaa R. Abdelmohsen,
Amira M. Negm,
Azza S. Khalil,
Ayat M. S. Eraque,
Reem M. Ahmed,
Walaa S. Sabbah,
Ahmed A. Ahmed,
Samah E. Ibrahim
Affiliations
Rania A. Elrashidy
Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
Esraa M. Zakaria
Pharmacology Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
Rehab A. Hasan
Histology and Cell Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Asmaa M. Elmaghraby
Histology and Cell Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Dina A. Hassan
Histology and Cell Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Ranya M. Abdelgalil
Anatomy and Embryology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Shaimaa R. Abdelmohsen
Anatomy and Embryology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Amira M. Negm
Medical Physiology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Azza S. Khalil
Medical Physiology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Ayat M. S. Eraque
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Reem M. Ahmed
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Walaa S. Sabbah
Anatomy and Embryology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Ahmed A. Ahmed
Medical Student, Faculty of Medicine, Kasr Al Ainy, Cairo University, Cairo, Egypt
Samah E. Ibrahim
Medical Physiology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Objectives: Distant liver injury is a complication of renal ischemia-reperfusion (I/R) injury, which imposes mortality and economic burden. This study aimed to elucidate the cross-talk of endoplasmic reticulum (ER) stress and mitochondrial perturbations in renal I/R-induced liver injury, and the potential hepatoprotective effect of azilsartan (AZL).Methods: Male albino Wister rats were pre-treated with AZL (3 mg/kg/day, PO) for 7 days then a bilateral renal I/R or sham procedure was performed. Activities of liver enzymes were assessed in plasma. The structure and ultra-structure of hepatocytes were assessed by light and electron microscopy. Markers of ER stress, mitochondrial biogenesis and apoptosis were analyzed in livers of rats.Results: Renal ischemic rats showed higher plasma levels of liver enzymes than sham-operated rats, coupled with histological and ultra-structural alterations in hepatocytes. Mechanistically, there was up-regulation of ER stress markers and suppression of mitochondrial biogenesis-related proteins and enhanced apoptosis in livers of renal ischemic rats. These abnormalities were almost abrogated by AZL pretreatment.Discussion: Our findings uncovered the involvement of mitochondrial perturbations, ER stress and apoptosis in liver injury following renal I/R, and suggested AZL as a preconditioning strategy to ameliorate remote liver injury in patients susceptible to renal I/R after adequate clinical testing.
