Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A(2) enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury


ÇAKIR M., TEKİN S. , TAŞLIDERE A. , Cakan P., DÜZOVA H. , Gul C. C.

JOURNAL OF CELLULAR BIOCHEMISTRY, cilt.120, ss.3822-3832, 2019 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 120 Konu: 3
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/jcb.27664
  • Dergi Adı: JOURNAL OF CELLULAR BIOCHEMISTRY
  • Sayfa Sayıları: ss.3822-3832

Özet

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A(2) (PLA(2)) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-(p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA(2) enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.