Protective role of melatonin in ochratoxin a toxicity in rat heart and lung

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by different fungi. The most pronounced adverse effect of OTA is hepatonephrotoxicity. Melatonin (MEL) has an antioxidant effect and has free-radical scavenger properties. The effects of OTA on heart and lung tissue and possible ameliorating effects of MEL were investigated in rats. Twenty-four rats were allocated to three groups (each with eight rats): control; OTA-treated group (OTA dose 289 microg kg(-1) per day); and OTA + MEL-treated group (MEL dose 10 mg kg(-1) per day). After 30 days of treatment, the histopathological changes in the heart and lung of all groups were examined. Compared with the control rats, myocardial tissue of rats treated with OTA showed extensive cytoplasmic vacuole formation, necrosis of the myocytes, dissolution of the nucleus, clumped fibres, fibrillolysis, swollen myocardial fibres, small haemorrhagic areas and hyperaemic vessels (P <0.05). In addition, lungs of rats treated with OTA showed alveolar congestion, alveolar cell hyperplasia, prominent alveolar septal vessels, variable intensity loss of alveolar architecture, intraparenchymal inflammatory infiltration, intraparenchymal hyperaemic vessels, respiratory epithelial proliferation, perivascular and peribronchial inflammation, pneumonic infiltration, distorted appearance of lung parenchyma and emphysematous areas (P <0.05). In comparison with the OTA groups, the ameliorating effects of MEL in the lung damage parameters were on alveolar cell hyperplasia, prominent alveolar septal vessels, variable intensity loss of alveolar architecture, intraparenchymal inflammatory infiltration, perivascular inflammatory inflammation, distorted appearance of lung parenchyma and focal emphysematous areas in lung (P <0.05). Melatonin also significantly reduced myocardial damage in most of the parameters: extensive cytoplasmic vacuole formation, necrosis of the myocytes, clumped fibres, fibrillolysis, small haemorrhagic areas and hypaeremic vessels in heart (P <0.05). On the other hand, MEL did not lower the degree of damage in lung and heart to the level of the control rats, except for the parameters of the interstitial oedema and small haemorrhagic areas only in myocardial tissue. Histopathological findings showed that OTA induced damage in heart and lung and MEL treatment significantly reduced the degree of damage.

Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway

“…Compared with the OTA group, the ASX+OTA group significantly improved the adverse status of mice. At the end of the test, OTA significantly reduced body weight and heart weight, decreased heart rate, increased QT and RR intervals, and caused abnormal ECG changes in mice, which was consistent with previous studies [11,12,25,26]. This study identified pathological changes in the heart by HE staining and ultrastructural changes in the heart by transmission electron microscopy.…”

“…It has been shown that OTA administration to rats (288.8 μg/kg) by gavage led to accumulation in the lung, liver, kidney, heart, fat, intestine, and testis of rats [10]. Okutan et al reported that low doses of OTA caused pathological damage to the rat heart as well as myocardial cell necrosis, myocardial fiber swelling, and vascular congestion [11]. Acute OTA exposure caused ultrastructural changes in the myocardium of rats [12].…”

Ochratoxin A-Induced Mutagenesis in Mammalian Cells Is Consistent with the Production of Oxidative Stress

“…It is interesting to mention that, similarly to OTA, reactive species derived from NO have been shown to induce an increase of spontaneous mutagenesis (62). OTA indeed induces oxidative and nitrosative stress (17,51,(63)(64)(65)(66)(67)(68)(69), and as expected, antioxidants are able to prevent its toxic effects (70)(71)(72)(73)(74). Different mechanisms for oxygen and nitrogen radical production by OTA have been proposed as follows: (i) oxido-reduction mechanisms directly involving OTA and Fe 3+ (68,75), (ii) perturbation of Ca 2+ homeostasis (65,66), (iii) generation of hydroquinone/quinone species from OTA oxidation (64,(76)(77)(78), (iv) OTA-mediated reduction of antioxidant cellular defenses (73), and (v) induction of the expression of inducible nitric oxide synthase (iNOS) (79) that is dominantly expressed during inflammatory reactions.…”

Immunotoxic activity of ochratoxin A

“…Necrotic changes were observed in rat liver (Aydin et al. , 2003), rat myocytes (Okutan et al. , 2004), and in germinal centers of spleen and lymph nodes of Wistar rats (Kanisawa et al.…”

“…In addition to apoptosis, necrosis also occurred under OTA burden. Necrotic changes were observed in rat liver (Aydin et al, 2003), rat myocytes (Okutan et al, 2004), and in germinal centers of spleen and lymph nodes of Wistar rats (Kanisawa et al, 1977) and dogs (Kitchen et al, 1977). The type of cell death stimulated by OTA appears to be determined by the dose and exposure time.…”