Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats.

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

Zearalenone-induced changes in biochemical parameters, oxidative stress and apoptosis in cardiac tissue: Protective role of crocin.

Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in food commodities and is known to cause reproductive disorders. Several in vivo studies have shown that ZEN is haematotoxic and hepatotoxic and causes several alterations of immunological parameters. Meantime, the available information on the cardiotoxic effects of ZEN is very much limited. In the present study, we investigated the toxic effects of ZEN in heart tissues of Balb/c mice. We demonstrated that ZEN (40 mg kg(-1) body weight (b.w.)) increased creatine phosphokinase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, total cholesterol and triglyceride levels and induced oxidative stress as monitored by measuring the malondialdehyde level, the generation of protein carbonyls, the catalase and superoxide dismutase activity and the expression of the heat shock proteins (Hsp 70). We also demonstrated that acute administration of ZEN triggers apoptosis in cardiac tissue. Furthermore, we aimed to evaluate the safety and efficacy of crocin (CRO), a natural carotenoid, to prevent ZEN-induced cardiotoxicity in mice. In fact, combined treatment of ZEN with different doses of CRO (50, 100, and 250 mg kg(-1) b.w.) showed a significant reduction of ZEN-induced toxicity for all tested markers in a dose-dependent manner. It could be concluded that CRO was effective in the protection against ZEN-induced toxicity in cardiac tissue.

Monosporascus eutypoides, a Cause of Root Rot and Vine Decline in Tunisia, and Evidence that M. cannonballus and M. eutypoides Are Distinct Species.

Three Monosporascus eutypoides-like isolates recovered from cucurbit plants with symptoms of Monosporascus root rot and vine decline in Tunisia were compared to 28 isolates of M. cannonballus from 12 countries for phenotypic, genomic, and pathogenicity characteristics. Morphologically, M. cannonballus and M. eutypoides-like cultures were similar, each producing fertile perithecia in culture containing globose, smooth, dark brown to black ascospores. Nevertheless, all M. cannonballus isolates had one ascospore per ascus, while M. eutypoides-like isolates had mainly two to three ascospores per ascus (rarely one). The employment of the internal transcribed spacer (ITS) of nuclear ribosomal DNA, the elongation factor 1-α (EF-1α), and the ß-tubulin (ß-tub) gene sequence diversity analyses and the resulting phylogenies identified a level of polymorphism that enabled separation of M. cannonballus and M. eutypoides-like isolates. All isolates of M. cannonballus had identical EF-1α and ß-tub sequences irrespective of very diverse geographic origins, which were different from the EF-1α and ß-tub sequences of the M. eutypoides-like isolates (96 and 97% similarity, respectively). Similar results were obtained for the ITS region of rDNA. In addition, of three M. eutypoides-like isolates tested for pathogenicity, all three were pathogenic on watermelon, two were pathogenic on muskmelon, but only one was pathogenic on cucumber. The results demonstrate that the M. eutypoides-like isolates belong to the species M. eutypoides, and that M. cannonballus and M. eutypoides are distinct species.

Protective effect of aqueous extract of Allium sativum against zearalenone toxicity mediated by oxidative stress.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. Several reports suggest that oxidative damage seems to be a key determinant of ZEN induced toxicity in vitro and in vivo. The aim of the current study was to evaluate the protective effects of aqueous extract of Allium sativum (AEA), against ZEN-induced cytotoxicity, reactive oxygen species (ROS) generation and DNA fragmentation in cultured Vero cells. Indeed, cytotoxicity effects were studied using MTT viability assay, ROS generation measurement and catalase activity induction. To check whether the oxidative stress induction was associated to DNA lesions, we looked for DNA fragmentation using Comet test. Our results indicated that ZEN induced several toxic effects and significant alterations mediated by oxidative stress mechanism. Treatment by ZEN combined to the lowest dose of AEA (250 µg/ml) showed a significant reduction of ZEN induced damages for all tested markers and a noticeable reduction of DNA fragmentation. It could be concluded that A. sativum aqueous extracts is effective in the protection against ZEN hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental toxic effects mediated by oxidative stress process and therefore prevents multiple human diseases.

Differences in preovulatory follicle dynamics and timing of preovulatory LH surge affect fertility of maiden sheep reared in semi-arid extensive conditions.

In the current study follicular dynamics, pituitary function, ovulatory response and luteal activity of 30 maiden Barbarine sheep were analyzed according to oestrus occurrence and lambing outcome after oestrus synchronisation with cloprostenol. Animals were retrospectively classified in three groups named as O- (n=7, ewes not displaying oestrus), O+L- (n=7, ewes showing oestrus but failing to lamb) and O+L+ (n=16; ewes showing oestrus and lambing thereafter). All the sheep ovulated and daily transrectal ultrasonographies revealed that preovulatory follicles were present at cloprostenol injection in all the animals. In sheep O+L+ and O+L-, 50% and 57% of the ovulatory follicles were the largest follicles at cloprostenol treatment (mean size of 4.1+/-0.26 mm and 4.3+/-0.74 mm, respectively). In O- ewes, the same percentage was higher (86%, P<0.05 when compared to group O+L+; mean size of 4.0+/-0.46 mm). The number of large follicles and the final diameter of the ovulatory follicles at oestrous tended thereafter to be higher in group O+L+ (1.4+/-0.1 and 6.4+/-0.2) than in groups O+L- (1+/-0.2 and 5.7+/-0.36) and O- (0.9+/-0.2 and 5.9+/-0.5, respectively). Conversely, the number of medium follicles at oestrus detection was higher in the group O+L- (2.1+/-0.3, P<0.05) than in the other two groups (1+/-0.2 and 1+/-0.3 for O+L+ and O- respectively). Timing of preovulatory LH surge was earlier for ewes O- (24.0+/-4.75, P<0.05) than for sheep O+L+ and O+L- (37.9+/-2.45 h and 38.0+/-4.75 h, respectively) and 94% of O+L+ ewes had a LH surge between 16 h and 64 h after cloprostenol injection compared to 57% in O+L- and O- groups (P<0.05). Thus, maiden Barbarine sheep failing to display oestrus or conceive showed alterations in their follicular dynamics and, thereafter, pituitary function and ovulatory response.