Crosstalk among apoptosis, inflammation, and autophagy in relation to melatonin protective effect against contrast-induced nephropathy in rats

Abstract

Contrast medium (CM) is a chemical substance that is used for imaging anatomical boundaries and to explore normal and abnormal physiological findings; the use of CM was associated with kidney injury and acute renal failure. Melatonin (M) possesses antioxidant, anti-inflammatory, and antiapoptotic effects in addition to autophagy modulation. This study aimed to investigate the protective effect of M against contrast-induced nephropathy (CIN) and its impact on the crosstalk between inflammasome, apoptosis, and autophagy in CIN. Male albino rats received M (10, 20, and 40 mg/kg/day, intraperitoneally) for 3 days. One hour after the last administration, rats were subjected to CIN induction (10 mg/kg indomethacin, double doses of l-NAME 10 mg/kg, i.v., and meglumine diatrizoate 60% 6 mL/kg, i.v.). CIN-induced kidney damage was evidenced through elevated kidney function biomarkers and induced renal histopathological changes. Pretreatment with M caused a significant decrease in nephrotoxicity biomarkers and histopathological alterations. Moreover, CIN-induced oxidative stress, NLRP3 inflammasome, and apoptosis were attenuated by M. Furthermore, M modulates autophagy in CIN rats. M inhibits CIN-induced NLRP3-inflammasome activation and apoptosis as well as enhances autophagy.

Endogenous and Exogenous Antioxidants as Agents Preventing the Negative Effects of Contrast Media (Contrast-Induced Nephropathy)

“…Association of bilirubin level with CIN was found in [124,125,139]; induction of HO-1 (on animals) [140] Melatonin positive on animal models [146,149,[152][153][154][155] L-carnitine positive on humans [162][163][164][165] Statins positive on humans [170][171][172][173], meta-analyses [174][175][176][177], on animals [178,179] controversial on humans [180] Probucol positive on humans [181,182], meta-analyses [183,185] no results on humans, meta-analysis [184] MESNA positive on humans [190,192] Resveratrol positive on animal models [195,196], in vitro [197][198][199][200] Astaxanthin positive on animal models [204][205][206][207] Table 1. Cont.…”

“…It was shown in a mice model that melatonin mitigates CIN by the activation of Sirtuin-3 (Sirt3), which attenuates tubular epithelial cell apoptosis, oxidative stress and mitochondrial dysfunction [ 146 ]. Melatonin was shown (in rats) to attenuate oxidative stress, NLRP3 inflammasome and apoptosis induced by CIN [ 155 ]. Recently, it was concluded that supplementation with melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis and oxidative stress occur regardless of the mechanism [ 149 ].…”

Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment

“…The immunomodulator rapamycin reduces the apoptosis of renal tubular epithelial cells and protects against CI-AKI by up-regulating Parkin expression, enhancing mitophagy, alleviating mitochondrial damage and oxidative stress caused by ROS overproduction. In addition, melatonin can significantly mitigate renal toxicity biomarkers and kidney damage by repressing oxidative stress, the NLRP3 inflammasome activation, and apoptosis in CI-AKI by activating autophagy [ 81 ]. Recent work has highlighted that inhibition of autophagy can aggravate CI-AKI.…”