Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway

Abstract

Background/Aims: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue’s NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. Methods: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method. All groups’ β2-MG in urine in 24h, serum Cr and BUN were compared, and UAER were calculated. Nitric oxide synthase (NOS), cGMP-dependent protein kinase (PKG), Caspase-3 expression were all determined by western blot. Nitric oxide (NO), NOS and cGMP levels were also examined by using ELISA. All groups’ nephridial histomorphology and kidney tubules score were evaluated and compared. Results: β2-MG and UAER in urine, serum Cr and BUN, in renal tissue were all elevated in Model of RIRI, indicating the success of animal model of RIRI establishment, and above index in CUR + Model group were all lower than those in Model group. Furthermore, iNOS, NO, cGMP, PKG and Caspase-3 in renal tissue were all increased in Model of RIRI, indicating the NO signaling pathway was activated, which is one of the pathogenesis of RIRI, and above index in CUR + Model group were all lower than those in Model group, suggesting that inactivation of iNOS/NO/cGMP/PKG signaling pathway is one of the reasons that explain the protective effect of curcumin in RIRI. Conclusion: The activation of iNOS/NO/cGMP/PKG signaling pathway and the consequent promoted apoptosis of renal tubules are significantly involved in the pathogenesis of development of RIRI, and curcumin treatment could protect renal tubules against RIRI, at least partially, by suppressing the activated iNOS/NO/cGMP/PKG signaling pathway.

Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase

“…The detected decrease in serum NO level in AP group treated with curcumin in our study may be due to inhibition of induction of iNOS, which resulted in decrease in NO level, which is in agreement with Liu et al (2017) who have demonstrated that the iNOS/NO signaling pathway was suppressed with curcumin treatment indicating that the preventive effect of curcumin could be mediated by its ability to suppress the transcription of iNOS and attenuate the downstream signaling pathway of iNOS/NO. iNOS rather than eNOS is the major NOS that is responsible for the dramatic increase in the production of NO and activation of the signaling pathway.…”

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

“…However, curcumin, apocynin and diphenyliodonium have antioxidant functions that inhibit nitric oxide synthesis, xanthine oxidase, cytochrome P450 reductase, and mitochondrial enzymes. For these reasons, definitively attributing the neutralization of ischemia-reperfusion injury by apocynin and diphenyliodonium to NOX enzyme inhibition is difficult [62-67]. …”

Mammalian STE20-Like Kinase 1 Deletion Alleviates Renal Ischaemia-Reperfusion Injury via Modulating Mitophagy and the AMPK-YAP Signalling Pathway

“…Unfortunately, although reperfusion restores blood flow to infarcted kidney tissues, the reperfusion itself also induces additional damage to the kidney tissue, which is referred to as ischemia-reperfusion (I/R) injury [2, 3]. In spite of the extensive research that has been carried out over the past six decades in the field of renal IR injury [4, 5], the pathogenesis of reperfusion-mediated kidney damage is poorly understood [6]. …”