Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury.
Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p < 0.001) ameliorates increased serum creatinine and BUN. In parallel to this, pomegranate also exhibits anti-apoptotic activity through the reduction of active caspase-3 expression in kidneys. Additionally, in-silico studies also confirmed a renoprotective effect of pomegranate. The above findings suggest that pomegranate can be used as a dietary supplement in the treatment of cisplatin-induced kidney injury by reducing apoptosis, oxidative stress and inflammation.
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. surenderaiims@gmail.com.
Ritu
R
Karwasra
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. surenderaiims@gmail.com.
Prerna
P
Kalra
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. surenderaiims@gmail.com.
Yogendra Kumar
YK
Gupta
Department of Pharmaceutical Chemistry, Kurukshetra University, Kurukshetra 136119, India.
Deepika
D
Saini
Department of Pharmaceutical Chemistry, Kurukshetra University, Kurukshetra 136119, India.
Ajay
A
Kumar
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. surenderaiims@gmail.com.
Surender
S
Singh
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004610:Ellagic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015850:Interleukin-6; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D004610:Ellagic Acid; D005707:Gallic Acid; D003404:Creatinine; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D002945:Cisplatin