Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

Abstract

Cyclophosphamide (CP) is widely used in treatment of different cancers. Nephrotoxicity is one of the dose-limiting side effects of CP. This study was carried out to investigate the effect of melatonin (MEL) on CP-induced nephrotoxicity in mice. In this study, 50 Swiss albino mice (20-25 g) were randomly divided into five groups. Mice were pretreated with MEL intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days, and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose of MEL. Then on day 6, blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidneys were used for histological examination, biochemical assays and real-time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity were assessed in renal tissue. In addition, the expression of SOD2 and PGx1 was measured using real-time PCR method in renal tissue. Results showed that CP administration significantly increases Cr, BUN, MDA, PC, NO level and MPO activity. It also decreases renal GSH level, SOD, GPx and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days prevented these changes; however, it did not affect the SOD activity. Our results revealed that MEL might be useful for prevention of the nephrotoxicity induced by CP through ameliorative effects on biochemical indices and oxidative stress parameters.

Melatonin attenuates homocysteine‐induced injury in human umbilical vein endothelial cells

“…The data are in line with previous studies indicating that melatonin prevented LPO and ROS overproduction induced by acrylamide in PC12 cells [30]. It is also indicated that melatonin decreased LPO and reversed the cyclophosphamideinduced oxidative stress and nephrotoxicity in mice [31].…”

Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway

“…The present data thus indicate that SCHPs-F1 treatment significantly relieved CTX-induced renal oxidative stress, inflammatory responses, and apoptosis in mice, likely by enhancing the antioxidant protective system comprising GSH-Px, SOD, CAT, and T-AOC, and by suppressing the lipid peroxidation product MDA, the pro-inflammatory cytokines IL-1β, IL-6, TNF-α and IFN-γ, and the pro-apoptotic Bax/Bcl-2 ratio. It is known that acrolein has a severe adverse effect on the kidneys, which results in the robust activation of oxidative stress responses and further aggravation of renal injury [1,30,31]. GSH-Px, SOD, CAT, and T-AOC are critical indicators for evaluating the capacity of the cellular antioxidant defense system [32,33].…”

“…GSH-Px, SOD, CAT, and T-AOC are critical indicators for evaluating the capacity of the cellular antioxidant defense system [32,33]. An imbalance in oxidative stress defense leads to insufficient antioxidant responses and lipid peroxidation to generate MDA [31,34]. As mentioned, SCHPs-F1 increased the antioxidant defense parameters GSH-Px, SOD, CAT, and T-AOC and decreased levels of the lipid peroxidation marker MDA, thereby potentially alleviating oxidative stress of CTX-exposed kidneys.…”

Anxiolytic‐like effects of the new arylpiperazine derivatives containing isonicotinic and picolinic nuclei: behavioral and biochemical studies

“…Moreover, oxidative stress induces protein oxidation, DNA oxidation, and mitochondrial damage. ROS activity is balanced in the body by an antioxidant defense system (ADS), the main components of which are antioxidants and antioxidant enzymes . Depending on their operation, free radical production is substantially decreased, and that already formed are converted into O 2 or H 2 O.…”