Effects of Lycopene Alone or Combined with Melatonin on Methotrexate-Induced Nephrotoxicity in Rats

Abstract

Methotrexate (Mtx), used for its anticancer and immunsuppresive properties, is known to be a nephrotoxic agent. We aimed to investigate the effects of lycopene (Lyc) alone or combined with melatonin (Mel) on Mtxinduced nephrotoxicity since both of these agents have antioxidant and anti-inflammatory effects. Nephrotoxicity was induced by intraperitoneal administration of methotrexate at a dose of 20 mg/kg. Treatment both with Lyc alone and Lyc combined with Mel provided significant reduction in tumor necrosis factor-alpha, interleukin 1-beta and ceruloplasmin levels in Mtx administered rats. Hovewer, Lyc combined with Mel provided a significant reduction also in NO levels. Hstopathological examination showed that there was an obvious improvement in the degenerative changes compared to Mtx administrated group with the Lyc combined Mel group giving best protection. In conclusion Lyc alone and combined with Mel provided significant improvement against renal damage caused by Mtx, preseumably via antioxidant and anti-inflammatory activities.

Lycopene improves methotrexate-induced functional alterations of the Madin–Darby kidney cells in a concentration-dependent manner

“…Application of Lyc in combination with MTX prevented a decline in the MDCK cells' ability to metabolize MTT and to a certain extent to accumulate NR. These results align with previously reported beneficial properties of Lyc-in MTX-induced rat kidney damage in vivo (Stojiljković et al 2018;Oguz et al 2015).…”

“…The partially inconsistent results between in vivo and in vitro studies might be explained through different exposure/treatment time, metabolism of Lyc, and its interactions with different cellu- lar molecules. In the present in vitro study, we applied Lyc at fixed concentrations during 24 h on a single cell type, while in in vivo studies, the Lyc is mostly administered in various concentrations during several days and it most certainly affects different cell types (Stojiljković et al 2018;Ramanathan and Ramalakshmi 2017;Guil-Guerrero et al 2011;Oguz et al 2015). Additionally, in in vivo conditions, Lyc passes numerous metabolic "barriers" (i.e., enterocytes, liver, etc.…”

Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis

“…Supplementation of NDEA mice with LycT modulated the serum levels of these cytokines by inhibiting their production and induction of apoptosis thus showing its anti-inflammatory effect. Literature also supported the amelioration of these inflammatory markers upon administration of lycopene [47][48][49] . NDEA treatment also exhibited enhanced plasma LPO and reduced GSH levels in comparison to control and LycT animals.…”

Melatonin-lycopene combination improves methotrexate-induced liver toxicity in rats via anti-inflammatory effect

“…Moreover, the anti-inflammatory effects of MLT are well known (23). In a study, it is similar between LYC and LYC + Mel treated groups in levels of TNF-α and IL-1 β, in renal tissue (24). In the same study, the levels nitric oxide was similar with LYC and combination of LYC + MLT.…”