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Can J Physiol Pharmacol. 2019 May;97(5):422-428. doi: 10.1139/cjpp-2018-0641. Epub 2019 Feb 7.

Two different melatonin treatment regimens prevent an increase in kidney injury marker-1 induced by carbon tetrachloride in rat kidneys.

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a Medical Faculty, University of Niš, Clinical center Niš-Clinic of urology, Niš, Serbia.
b Clinical-Hospital Center, Pristina, Gracanica, Serbia.
c Faculty of Medicine, University of Priština, Kosovska Mitrovica, Serbia.
d Faculty of Medicine, University of Niš, Zorana Ðinđića 81, Niš, Serbia.


Acute kidney injury is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin is one of the most powerful natural antioxidants and has numerous beneficial properties. We evaluated the nephroprotective potential of 2 melatonin treatment regimens (pre- and post-intoxication) in a CCl4-induced acute kidney injury model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes. The two treatment regimens were found to preserve kidney function, as judged from the evaluated standard serum parameters. Only when administered after the intoxication, melatonin preserved total kidney antioxidant capacity; pre-treatment melatonin only preserved reduced glutathione levels. An increase in tissue KIM-1 level was found to be prevented by both treatment regimens, which correlated with the morphological changes seen in the kidney tissues of animals treated with melatonin and CCl4. The findings of our study are in agreement with the known actions of melatonin in relieving kidney tissue oxidative burden, but also contribute to the understanding of its action by preventing an increase in KIM-1.


KIM-1; carbon tetrachloride; changements mitochondriaux; insuffisance rénale; kidney damage; lésions oxydatives; melatonin; morphological changes; mélatonine; oxidative damage; tétrachlorure de carbone


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