Role of progesterone in melatonin-mediated protection against acute kidney injury Q6 Jyotsna Sehajpal, a Tajpreet Kaur, b Rajbir Bhatti, a and Amrit Pal Singh a, * a Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India Q1 b Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, Punjab, India article info Article history: Received 14 February 2014 Received in revised form 8 April 2014 Accepted 9 April 2014 Available online xxx Keywords: Melatonin Progesterone Kidney Ischemia Oxidative stress 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 Q2 present study investigated the involvement of progesterone re- ceptors in melatonin-mediated protection against ischemia reperfusion induced acute kidney injury (AKI) in rats. Materials and methods: The rats were subjected to bilateral renal ischemia for 40 min fol- lowed 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 hematoxylineeosin 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 abol- ished 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. ª 2014 Elsevier Inc. All rights reserved. 1. Introduction Acute kidney injury (AKI) is characterized by reduced glomer- ular filtration rate and sudden decline in kidney function that results in accumulation of nitrogenous and other biochemical wastes in body. AKI accounts for 1% of hospital admissions and around 7% in hospitalized patients [1]. The patients with AKI have mortality rate of 10% that increases to 80% in cases with renal replacement therapy. AKI is a major risk factor for non- renal complications such as sepsis, delirium, and respiratory failure [2]. Ischemia is a state of blood and oxygen deprivation to a tissue resulting in reduced washout of metabolites. The reperfusion resumes blood supply to ischemic areas but itself initiates cascade of adverse reactions that cause damage to the * Corresponding author. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab, India. Tel.: þ91- 183-2258802-09x3467, þ91 985 545 5354; fax: þ91 183225 8819. E-mail address: apsingh82@gmail.com (A.P. Singh). Available online at www.sciencedirect.com ScienceDirect journal homepage: www.JournalofSurgicalResearch.com journal of surgical research xxx (2014) 1 e7 0022-4804/$ e see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.04.025 5.2.0 DTD  YJSRE12693_proof  30 April 2014  8:36 pm  ce 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129