Involvement of progesterone receptors in ascorbic acid-mediated protection against ischemia-reperfusion-induced acute kidney injury.
BACKGROUND
Ascorbic acid (AA) is an established antioxidant and has been used for treatment of various disorders. Recent reports suggest that administration of AA increases the level of steroids such as progesterone in the body. The present study investigated the protective role of progesterone against ischemia-reperfusion-induced acute kidney injury (AKI) and possible involvement of progesterone receptors in AA-mediated renoprotection in rats.


METHODS
The male rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The rats were treated with progesterone (5 and 10 mg/kg, intraperitoneally) and AA (500 mg/kg, intraperitoneally for 1, 2, and 5 d) before AKI. In separate groups, mifepristone, the progesterone receptor antagonist was administered to rats before progesterone (10 mg/kg) and AA treatment (5 d). Various parameters including creatinine clearance, serum urea, uric acid, potassium level, fractional excretion of sodium, lactate dehydrogenase, and microproteinuria were used to assess kidney injury. Moreover, renal tissues were subjected to quantification of oxidative stress and evaluation of histopathologic changes.


RESULTS
The exogenous administration of progesterone afforded protection against AKI in a dose-dependent manner that was abolished by mifepristone. The administration of AA for 1, 2, and 5 d induced significant increase in serum progesterone levels and afforded protection against AKI. The antioxidant and renoprotective effect of AA was abolished by prior treatment with mifepristone.


CONCLUSIONS
It is concluded that exogenous administration of progesterone exerts significant antioxidant and renoprotective effect. Moreover, the progesterone receptors find their explicit involvement in AA-mediated renoprotection against ischemia-reperfusion-induced AKI in rats.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
Jasmine
J
Sandhi
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
Jaswinder Pal
JP
Singh
Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, Punjab, India.
Tajpreet
T
Kaur
Department of Veterinary Gynaecology and Obstetrics, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India.
Sarvpreet Singh
SS
Ghuman
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India. Electronic address: apsingh82@gmail.com.
Amrit Pal
AP
Singh
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011188:Potassium / Q000097:blood; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011980:Receptors, Progesterone / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood
D000975:Antioxidants; D011980:Receptors, Progesterone; D014527:Uric Acid; D011374:Progesterone; D014508:Urea; D007501:Iron; D001205:Ascorbic Acid; D011188:Potassium
Acute kidney injury; Ascorbic acid; Ischemia-reperfusion; Oxidative stress; Progesterone