Physiological and pharmacological concentrations of melatonin protect against cisplatin‐induced acute renal injury

Abstract

Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side-effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham-operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP-induced renal injury.

Beneficial Effects of Montelukast against Cisplatin-Induced Acute Renal Damage in Rats

“…Although the mechanisms of CP-induced nephrotoxicity are not fully understood, one mechanism of this toxicity is believed to involve ROS generation and inflammatory machine in the pathophysiology of CP-induced ATN after even a single dose of the drug. 4,[29][30][31] These agents likely account for the pathophysiology of CP-induced nephrotoxicity. CP-induced nephrotoxicity is the main adverse effect, and monitoring its plasma concentration is therefore recommended.…”

“…Behind the therapeutic effect of montelukast, the aim of this study was to investigate the possible protective effects of montelukast; therefore, montelukast was administered before CP treatment. Moreover, 24 h after the last injection, a time chosen according to a CP-related study, 4 all rats were killed and the kidneys were quickly removed, decapsulated, and divided equally into two longitudinal sections. One half was placed in formaldehyde solution for routine histopathological examination by light microscopy.…”

“…The mechanisms of CP-induced nephrotoxicity are not fully understood. 3,4 The primary targets of CP in the kidneys are proximal convoluted, straight, and distal convoluted tubules, where it accumulates and promotes cellular damage. 5,6 There are many studies concerning the role of reactive oxygen radical species (ROS) in the pathophysiology of CP-induced nephrotoxicity.…”

The Antioxidant Effect of Melatonin on Myocardial Ischemia Reperfusion Injury in Experimental Studies

“…Melatonin reduces the I/R damage to the other organs such as the kidney [14], testis [30] and liver [31] in rats. Similarly, melatonin protects against cardiotoxicity induced by chemotherapeutic drugs, which are often in cardiac tissue [32].…”

“…Melatonin has more potent free radical scavenging properties against OH-from all known antioxidants. Since the functions of the pineal gland and melatonin levels decrease with aging, these circumstances lead to decrease and increase the diseases, to decrease antioxidant capacity and the diseases associated with an increased oxidative stress (Fig 3) [14,15]. Normal level: 60-70 pg/ml…”