The aim of this study was to investigate electromagnetic radiation (EMR) transmitted by wireless devices (2.45 GHz), which may cause physiopathological or ultrastructural changes, in the testes of rats. We addressed if the supplemental gallic acid (GA) may reduce these adverse effects. Six-week-old male Sprague Dawley rats were used in this study. Forty eight rats were equally divided into four groups, which were named: Sham, EMR only (EMR, 3 h day for 30 days), EMR + GA (30 mg/kg/daily), and GA (30 mg/kg/daily) groups. Malondialdehyde (MDA) and total oxidant status (TOS) levels increased (p = 0.001 for both) in EMR only group. TOS and oxidative stress index (OSI) levels decreased in GA treated group significantly (p = 0.001 and p = 0.045, respectively). Total antioxidant status (TAS) activities decreased in EMR only group and increased in GA treatment group (p = 0.001 and p = 0.029, respectively). Testosterone and vascular endothelial growth factor (VEGF) levels decreased in EMR only group, but this was not statistically significant. Testosterone and VEGF levels increased in EMR+GA group, compared with EMR only group (p = 0.002), and also increased in GA group compared with the control and EMR only group (p = 0.044 and p = 0.032, respectively). Prostaglandin E (PGE ) and calcitonin gene releated peptide (CGRP) staining increased in tubules of the testes in EMR only group (p < 0.001 for both) and decreased in tubules of the testes in EMR+GA group (p < 0.001 for all parameters). In EMR only group, most of the tubules contained less spermatozoa, and the spermatozoon counts decreased in tubules of the testes. All these findings and the regenerative reaction, characterized by mitotic activity, increased in seminiferous tubules cells of the testes in EMR+GA group (p < 0.001). Long term EMR exposure resulted in testicular physiopathology via oxidative damage and inflammation. GA may have ameliorative effects on the prepubertal rat testes physiopathology. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1771-1784, 2016.

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

Parkinson's disease (PD) is the second most common neurodegenerative disease. In recent years, it has been shown that leucine-rich repeat kinase 2 (LRRK2) has a crucial function in both familial and sporadic forms of PD. LRRK2 pathogenic mutations are thought to result in an increase in LRRK2 kinase activity. Thus, inhibiting LRRK2 kinase activity has become a main therapeutic target. Many compounds capable of inhibiting LRRK2 kinase activity with high selectivity and brain availability have been described. However, the safety of long-term use of these ATP-competitive LRRK2 kinase inhibitors has been challenged by several studies. Therefore, alternative ways of targeting LRRK2 activity will have a great benefit. In this review, we discuss the recent progress in the development of allosteric inhibitors of LRRK2, mainly via interfering with GTPase activity, and propose potential new intra and interprotein interactions targets that can lead to open doors toward new therapeutics.

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Objective: Endoplasmic reticulum stress (ERS) and neuroinflammation are triggers for neurodegenerative disorders. Salubrinal is a selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phosphorylated eukaryotic initiation factor-2a (eIF2a), the key crucial pathway in the ERS. Therefore, this study assessed the effects of inhibition of the ERS with salubrinal in the intranigral hemi-Parkinson disease (PD) model. Materials and methods: Animals were treated with salubrinal for one week after the PD model was created by intranigral lipopolysaccharide (LPS) administration. Apomorphine-induced rotation, rotarod, cylinder, and pole tests were performed to evaluate behavioral changes. Proinflammatory cytokines and the expression level of the dual specificity protein phosphatase 2 (DUSP2), PP1, and p-eIF2a were evaluated. Nigral expression of inducible nitric oxide synthase (iNOS), nuclear factor kappaB (Nf-jB), and cyclooxygenase (COX)-2 was determined. Finally, tyrosine hydroxylase and caspase-3/ caspase-9 expressions were assessed by immunohistochemistry. Results: Salubrinal reduced the motor impairments and dopamine-related behavioral deficiencies caused by the LPS. Salubrinal attenuated the LPS-induced increased levels of interleukin (IL)-1b, IL-6, tumor necrosis factor-a, and salubrinal rescued the loss of TH expression and dopamine levels and prevented the caspase-3/9 increase in the substantial nigra (SN). LPS potently increased iNOS, Nf-jB, and COX-2 expression, but this effect was reduced after salubrinal treatment. Additionally, salubrinal attenuated the LPS-induced PP1 and DUSP2 increase. Conclusion: Our results reveal that salubrinal is attenuating several inflammatory mediators and thereby decreased the inflammatory effects of LPS in the neurons of the SN. Together this results in increased cellular survival and maintained integrity of SN. Taken together our data show the beneficial effects of inhibition of ERS to restrict neuroinflammatory progression and neuronal loss in a PD model.