Prophylactic administration of carnosine and melatonin abates the incidence of renal toxicity induced by an over dose of titanium dioxide nanoparticles

Abstract

The alleviative effects of two antioxidants, carnosine (Car) and melatonin (Mel), against titanium dioxide nanoparticles (TiO -NPs) toxicity-induced oxidative and inflammatory renal damage were examined in rats. Administration of these antioxidants along with TiO -NPs effectively reduced serum urea, uric acid, creatinine, glucose, tumor necrosis factor-α, interleukin-6, C-reactive protein, immunoglobulin G, vascular endothelial growth factor, and nitric oxide, as well as a significant amelioration of the decrease in glutathione levels in renal tissue was observed, compared to those in rats treated with TiO -NPs alone. The renoprotective properties of the antioxidants were confirmed by reduced intensity of renal damage as demonstrated by histological findings. In conclusion, Car and Mel play protective roles against TiO -NPs-induced renal inflammation and oxidative injury, likely due to their antioxidant and anti-inflammatory properties.

<p>Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods</p>

“…In the atelectatic areas, blackish-brown pigmented particles were found in the cytoplasm of macrophages or extracellularly, the latter surrounded by focal minimal lymphocytosis, hyperemia, and non-specific extravasation, as also seen previously. 16 In contrast, the structure of the kidney cortex and medulla was not altered in any of the treated groups. No inflammatory reaction or focal extravasation was induced by the nanorods.…”

“…In the lungs of rats treated identically in a previous study, several pro-inflammatory cytokines (such as IL-1α and CINC1) were elevated, and these findings are in line with the changes of the oxidative stress indicators presented in this study. 16 Light microscopy of HE stained lung sections showed histological alterations in the nano-TiO 2 treated rats. Intermingled areas with mild atelectasis or emphysema were seen with destroyed alveolar septa in the latter.…”

“…15 The kidneys, exerting the function of removing xenobiotics, showed oxidative stress, increased inflammation markers, as well as functional and histological damages due to tubular necrosis in rats treated orally with (unspecified) nano-TiO 2 . 16 In another study, lipid peroxidation, reduced antioxidant activity, and proximal tubular apoptosis has been observed in the kidneys of rats after oral administration of spherical TiO 2 NPs of <100 nm in size for 3 weeks. 17 Inhaled NPs can reach the brain by crossing the alveolar and blood-brain barriers (BBB) or by migrating along olfactory and other afferent nerve fibers.…”

Morphofunctional state of rat kidneys under the conditions of cisplatin-induced acute kidney injury and its correction by melatonin

“…In our opinion, these nephroprotective effects may be explained first and foremost by the powerful antioxidant properties of this hormone at the level of the renal tubular cells -both direct antioxidant effect of the "scavenger" of free radicals, and indirect as a stimulator of antioxidant enzymes activity [1,7,26]. Probably, the anti-inflammatory effects of melatonin as a result of the inhibition of lipoxygenase activity may also contribute to the cytoprotective action of melatonin in conditions of cisplatin-induced AKI [12,13].…”

“…An important advantage of melatonin as a drug is a minimal risk of side effects, even when a high-dose therapy or a long-term treatment is used [9]. Multiple effects of melatonin, as well as its ability to affect the main pathogenetic links of the pathological process, give rise to the numerous experimental and clinical researches into the mechanisms of action and organoprotective potential of exogenous melatonin under the conditions of various pathologies, including renal [10][11][12].…”