Immunomodulatory and protective activity of combined treatment with curcumin and melatonin in damaged rat liver and lungs induced after renal ischemia-reperfusion (Is-Rp).

Ischemia and reperfusion (Is-Rp) of the kidney constitutes the leading cause of acute kidney injury (AKIn). This is an evolving process that is frequently linked to the failure of several organs. The distant organ injuries such as acute liver and lung injuries are the side effects of AKIn. In the current study, bilateral renal Is-Rp was induced in rats, and the impact of curcumin and melatonin on the lung and liver was investigated. Thirty-five adult rats, aged 10-12 weeks, were randomly assigned to five groups: the Control Group (Group 1), which underwent no surgical procedure. All other groups underwent 45 min of kidney ischemia, followed by 2 h of reperfusion. Group 2 was not administered any substance. Prior to reperfusion, the following treatments were applied: Group 3 received Is-Rp combined with melatonin (MEL), Group 4 received Is-Rp with curcumin (CUR), and Group 5 received Is-Rp with both MEL and CUR. Histological analysis was performed using Hematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), Toluidine Blue (TB), and Masson's Trichrome (TRI) staining techniques. The preparations were evaluated for changes, and severity was graded on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The scores were aggregated and presented as liver and lung injury indices for each rat. The liver tissues of the rats were assessed for leukocyte accumulation, fibrotic alterations, sinusoidal expansion, and vascular congestion. Simultaneously, the lung tissues were evaluated for alveolar collapse, intra-alveolar bleeding, mononuclear leukocyte presence within the alveoli, intravascular leukocyte accumulation, and necrotic changes. Statistically significant differences were observed among the groups in lung injury scores, liver injury scores, and mast cell counts (p < 0.000∗∗). The use of melatonin-curcumin together reduces distant organ damage caused by renal Is-Rp injury. The concurrent use of these two antioxidants exhibits a more effective therapeutic effect than their individual application.