Diphenyl diselenide prevents hepatic alterations induced by paraquat in rats

https://doi.org/10.1016/j.etap.2013.07.009Get rights and content

Highlights

  • We evaluated the protective effects of (PhSe)2 against hepatic injury induced by PQ.

  • We evaluated some parameters of oxidative stress, inflammation and hepatic damage.

  • The results show that (PhSe)2 has beneficial effects against PQ-induced injury.

  • This protection appears to involve the antioxidant and anti-inflammatory properties.

Abstract

This study aimed to investigate the beneficial effect of diphenyl diselenide (PhSe)2 on paraquat (PQ) induced alterations in rats liver. Adult male Wistar rats received (PhSe)2 at 10 mg kg−1, by oral administration (p.o.), during five consecutive days. Twenty-four hours after the last (PhSe)2 dose, rats received PQ at 15 mg kg−1, in a single intraperitoneally injection (i.p.). Seventy-two hours after PQ exposure, animals were sacrificed by decapitation for blood and liver samples obtainment. Histological alterations induced by PQ exposure, such as inflammatory cells infiltration and edema, were prevented by (PhSe)2 administration. Moreover, (PhSe)2 prevented hepatic lipid peroxidation (LPO) induced by PQ and was effective in reducing the myeloperoxidase (MPO) activity in liver, which was enhanced by PQ exposure. (PhSe)2 also was effective in protecting against the reduction in ascorbic acid and non-protein thiols (NPSH) levels induced by PQ. The inhibition of glutathione S-transferase (GST) activity, in rats exposed to PQ, was normalized by (PhSe)2 pre-treatment, whereas the inhibition of catalase (CAT) activity was not prevented by (PhSe)2. The serum alkaline phosphatase (ALP) inhibition, induced by PQ administration, was also prevented by (PhSe)2 pre-treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were not modified by PQ and/or (PhSe)2 administration. Therefore, (PhSe)2 pre-treatment was effective in protecting against the hepatic alterations induced by PQ in rats. This protective effect can involve the antioxidant and anti-inflammatory properties of (PhSe)2.

Introduction

Paraquat (PQ, 1,10-dimethyl-4,40-bipyridinium dichloride) is a commonly used herbicide. It is a fast acting and non-selective compound, which destroys tissues of green plants on contact and by translocation within the plant (Pasi, 1978). PQ is relatively nontoxic when used under the appropriate conditions. However, it has demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades (Pasi, 1978, Autor, 1977, Bismuth et al., 1990). The fatality rate resulting from PQ intoxications is still very high due to the lack of effective treatments (Dinis-Oliveira et al., 2008).

The biochemical mechanism of PQ toxicity involves its cyclic NADPH cytochrome c-catalyzed reduction and also its subsequent re-oxidation of the resulting PQ free radical by molecular oxygen. Being, then, the lung damages and pulmonary fibrosis the most widespread injuries and the majority causes of death (Mohammadi-Karakani et al., 2006). However, due to selective accumulation of PQ in the lungs, most of the previous studies focused on this organ. Consequently, there is little awareness of the effects of PQ at various forms of poisoning on other key organs including the liver (Malekinejad et al., 2010). Nevertheless, during the past decades a great number of studies have been conducted to clarify the toxic effects of PQ on liver tissue (Bando et al., 2007, Samai et al., 2008).

Recognizing that the mechanism in which the PQ induces its toxic effects is the oxidative stress one, researchers and clinicians have placed great emphasis on the use of antioxidants as a treatment modality for PQ toxicity (Suntres, 2008). Thus, organic forms of selenium (generally referred as organoselenium compound) have been suggested as possible antioxidant agents because they exhibit glutathione peroxidase-like activity (Mugesh et al., 2001, Nogueira et al., 2004). Diphenyl diselenide ((PhSe)2) is a specimen of this class. This organoselenium compound has beneficial effects in several studies, including improvements against damage from heavy metals (Brandão et al., 2008, Borges et al., 2008), neurotoxicity (Ghisleine et al., 2003), inflammation (Savegnago et al., 2007), anxiety (Savegnago et al., 2008) and lipid peroxidation (LPO) (Meotti et al., 2004). In this way, the aim of this study was to assess the potential protective capacity of the (PhSe)2 as pre-treatment against PQ-induced injury in rats liver.

Section snippets

Animals

Adult male Wistar rats from our own breeding colony (250–300 g) were used. The animals were kept on a 12 h light/dark cycle, with lights on at 7:00 a.m., at a room temperature of 22 ± 2 °C, with free access to food (Guabi, RS, Brazil) and water. Animals were used according to the guidelines of the Committee on Care and Use of Experimental Animal Resources of the Federal University of Santa Maria, Brazil.

Chemicals

(PhSe)2 was synthesized according to the literature method (Paulmier, 1986). Analysis of the 1H

Histological analysis

Histological analysis (Fig. 1) revealed cell swelling in liver lobules and sinusoidal dilatation in those animals exposed to PQ. Presence of nuclear hyperchromatism processes between hepatocytes and early cellular necrosis and edema formation was also observed. In animals exposed to PQ and pre-treated with (PhSe)2 the hepatic tissue is apparently normal. A reduction in sinusoidal dilatation and an absence of inflammation and tissue necrosis are also observed.

ALP, AST and ALT activities

Two-way ANOVA of ALP activity

Discussion

The present study revealed that the pre-administration of (PhSe)2 prevented the hepatic alterations induced by PQ in rats. This organoselenium compound was effective in preventing the histological alterations and LPO induced by PQ. In addition, (PhSe)2 prevented the decrease in ascorbic acid and NPSH levels, the inhibition in GST and ALP activities, as well as the increase in MPO activity provoked by PQ.

Our histological results suggest that treatment of rats with a toxic dose of PQ induces

Conflict of interest statement

All the authors declare that there are no conflicts of interest.

Acknowledgements

The financial support by FAPERGS, CAPES, and CNPq is grate fully acknowledged. Additional support was given by CNPq/FAPERGS/DECIT/SCTIE-MS/PRONEM #11/2029-1.

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