Antagonistic Effects of Melanin on Chromium-Induced Nephrotoxicity: Involvements of Inflammation, Oxidative Stress, and Mitochondrial Dysfunction

 Antagonistic Effects of Melanin on Chromium-Induced Nephrotoxicity: Involvements of Inflammation, Oxidative Stress, and Mitochondrial Dysfunction

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Abstract

Nephrotoxicity is a kidney-specific condition in which excretion fails to take place smoothly because of the negative effects of drugs or toxic chemicals. In the present study, the researchers investigated the potential of renoprotective effect and underlying mechanisms of Lachnum melanin (LM) using a rat model of potassium dichromate-induced nephrotoxicity. The rationale for using LM is based on the fact that research and empirical evidence have identified it as metal chelator with antioxidant properties. Nephrotoxicity was induced by a single injection of K2Cr2O7 (15 mg/Kg) and K2Cr2O7-treated animals were pre-treated by LM (sc, single dose) at three different doses (100, 200 and 300 mg/kg) 30 min before K2Cr2O7 administration. It was established that LM pre-treatment attenuated K2Cr2O7-induced renal dysfunction evaluated by serum creatinine, blood urea nitrogen, proteinuria, serum glutathione peroxidase activity, and urinary excretion of N-acetyl-d-glycosaminidase. Furthermore, it was also observed that LM prevented the K2Cr2O7-induced renal oxidant stress as well the decrease in the activity of the antioxidant. Moreover, K2Cr2O7-induced inflammation was reduced by treatment of LM by suppression of NFkr activities. It was further established that LM decreases the renal Cr(VI) content. Consequently, this empirical finding prompted the researchers to evaluate the potential Cr(VI) chelating properties of this compound. The researchers reported that pretreatment with LM significantly removed the mitochondria dysfunction by resorting the mitochondrial respiratory enzyme and antioxidant activities and decreased the elevated oxidative stress to normal. The nephroprotective effect of LM against Cr(VI)-induced nephrotoxicity may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content.

Keywords: Melanin; Potassium dichromate; Oxidative stress; Inflammation; Nephrotoxicity; Mitochondria

 

Antagonistic Effects of Melanin on Chromium-Induced Nephrotoxicity: Involvements of Inflammation, Oxidative Stress, and Mitochondrial Dysfunction

1.0 Introduction

Chromium, according to Collins et al. (2010), is a naturally-occurring element that ubiquitously exists in different oxidation states. However, the trivalent [Cr (III)] and hexavalent [Cr (VI)] shapes of this element are most essential from both natural and mechanical viewpoints. The toxicity and carcinogenicity of the Cr compound largely depends on the oxidation state as well as the solubility of the Cr types. The Cr(III)-containing compounds are generally insoluble and poorly absorbed from the gastrointestinal tract (Jannetto, Antholine, & Myers, 2001). In contrast, the Cr(VI)-containing compounds are highly water soluble and are easily transported across cell membranes by an anion carrier (Jannetto et al., 2001). Intracellular reduction of Cr (VI) to Cr(III) produce the massive amount of reactive oxygen species (ROS), which is an important characteristic of the Cr(VI) toxicity (Stohs, Bagchi, Hassoun & Bagchi, 2000). Potassium dichromate (K2Cr2O7) is a Cr(VI) form of Cr, and research has been demonstrated that this compound can induce nephrotoxicity in both humans and laboratory animals through an oxidative stress-mediated mechanism (Pedraza-Chaverrí et al., 2005). 

Suarez (2010) describes melanins as polyphenolic amorphous polymers that are widespread in plants, animals, and microbes (Suarez, 2010). On the other hand, Solano (2014) defines melanin as a generic name that is often used to refer to presumably the most heterogeneous, resistant, and ubiquitous pigments found in nature (Solano, 2014). The researcher argues that from a structural point of view, melanins represent “a group of complex pigments with a structure relatively diverse and undefined. Melanins have been widely and traditionally used in various industrial fields, for example, food, cosmetics, and medicine for their antioxidant effect as well as anti-quorum and anti-radiation sensing functionalities (Sun, Zhang, Chen, Zhang, & Zhu, 2016). Tarangini and Mishra (2014) acknowledge that melanin has shown in different model systems that it has several health beneficial properties, for example, metal chelating; anti-HIV, anti-radiation and immunity regulation; liver injury protection; and anti-oxidant action. Lachnum Melanin (LM) is a category of melanin that is derived from saprophytic fungi, which is capable of yielding large amounts of melanins using submerged fermentation approach (Ye et al., 2014).

Kidneys are a critical organ needed by the body to carry out several important functions, including the effective maintenance of the homeostatic balance, regulation of the extracellular environment, for instance, detoxification a