title: Role of progesterone in melatonin-mediated protection against acute kidney injury.
abstract: BACKGROUND
  Melatonin is released by pineal gland and maintains circadian rhythm in the body. It has been reported as renoprotective agent because of its antioxidant property. Recently, a cross talk between progesterone and melatonin has been observed in various preclinical studies. The present study investigated the involvement of progesterone receptors in melatonin-mediated protection against ischemia reperfusion induced acute kidney injury (AKI) in rats.
  
  
  METHODS
  The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, potassium level, fractional excretion of sodium, lactate dehydrogenase activity, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, reduced glutathione level, and catalase activity. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. The melatonin (4 and 10 mg/kg, intraperitoneally) and progesterone receptor antagonist mifepristone (5 mg/kg, intraperitoneally) were used in the present study.
  
  
  RESULTS
  The renal ischemia reperfusion induced AKI as indicated by significant change in serum, urinary, and tissue parameters that was ameliorated by prior treatment with melatonin. No significant difference in serum progesterone level was observed between various groups used in the present study. The prior administration of mifepristone abolished melatonin-mediated protection against AKI.
  
  
  CONCLUSIONS
  It is concluded that melatonin treatment affords protection against ischemia reperfusion induced AKI. Moreover, progesterone receptors are essentially involved in mediating protective role of melatonin against AKI in rats.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Sehajpal
authors.affiliation: Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, Punjab, India.
authors.forename: Tajpreet
authors.initials: T
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Bhatti
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India. Electronic address: apsingh82@gmail.com.
authors.forename: Amrit Pal
authors.initials: AP
authors.lastname: Singh
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D019610:Cytoprotection; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000097:blood / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015735:Mifepristone; D011374:Progesterone; D008550:Melatonin
keywords: Ischemia; Kidney; Melatonin; Oxidative stress; Progesterone