Amrit Pal Singh1, Nirmal Singh2, Preet Mohinder Singh Bedi3. 1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India. 2. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India. 3. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India. Electronic address: preet.pharma@gndu.ac.in.
Abstract
BACKGROUND: Estrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ) in estrogen-mediated protection against renal ischemia reperfusion injury (IRI) in rats. MATERIALS AND METHODS: The renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood urea nitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol A diglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-γ receptor antagonist, was given before estrogen administration followed by IRI in rats. RESULTS: The ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats. CONCLUSIONS: It is concluded that PPAR-γ agonism serves as one of the mechanisms in estrogen-mediated renoprotection.
BACKGROUND: Estrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ) in estrogen-mediated protection against renal ischemia reperfusion injury (IRI) in rats. MATERIALS AND METHODS: The renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood ureanitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol Adiglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-γ receptor antagonist, was given before estrogen administration followed by IRI in rats. RESULTS: The ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats. CONCLUSIONS: It is concluded that PPAR-γ agonism serves as one of the mechanisms in estrogen-mediated renoprotection.
Authors: Michael A Fawzy; Sherif A Maher; Mahmoud A El-Rehany; Nermeen N Welson; Nisreen K A Albezrah; Gaber El-Saber Batiha; Moustafa Fathy Journal: Molecules Date: 2022-02-18 Impact factor: 4.411
Authors: Claudia Weinheimer; Haimei Wang; Jessica M Comstock; Purneet Singh; Zhengming Wang; Brent A Locklear; Kasi L Goodwin; J Alan Maschek; James E Cox; Michelle L Baack; Lisa A Joss-Moore Journal: Reprod Sci Date: 2020-01-06 Impact factor: 3.060