Toxicology of long-term and high-dose administration of methylphenidate on the kidney tissue - a histopathology and molecular study.

The present study aims to assess the influences of oral methylphenidate on kidney function and structure versus vehicle treatment in adult male rats. In this study, thirty adult male rats equally into two treatment groups divided randomly, and among them, MPH has been administered for 21 days, at doses of 20 mg/kg, and the control group has received salin. In renal, under the effect of MPH applying quantitative real-time PCR, we analyzed nephrotoxicity-related molecular pathways like autophagy, inflammation, and apoptosis. Moreover, the levels of GSH, CAT, and SOD were investigated as antioxidant enzymes. Afterward, stereological analysis in MPH-treated rats has been performed. Analysis of qPCR displayed inflammation, impaired autophagy, and enhanced apoptosis with histological changes in the kidney's tissue, also an important rise in the antioxidant enzymes' level. Besides, 20 mg/kg of MPH led to a decline in the mean of Bowman's space thickness and renal corpuscle's volume in comparison to the control rats. Collectively, our histological and molecular data implicit that in the kidney region, administrating of MPH evoked discriminative expression alterations in nephrotoxicity-associated signaling cascades, specifically autophagy, inflammation, and apoptosis paired with important damage to kidney tissue.

A review of the protective effects of quercetin-rich natural compounds for treating ischemia-reperfusion injury.

Ischemia-reperfusion (IR) injury causes dysfunction of tissues and organs, and oxidative stress plays an important role. During IR, reactive oxygen species (ROS) are increased. Antioxidants are used to decrease ROS associated with IR. We review the protective effects of quercetin-rich natural antioxidants against IR. We searched PubMed, ScienceDirect, Scopus and Cochrane databases using the keywords: ischemic reperfusion, quercetin, antioxidant and herbal medicine. The effects of quercetin during IR have been reported for animal models in vitro and in vivo. Quercetin-rich plants including Abelmoschus esculentus, coriander, Hypericum perforatum, onion, Psidium guajava, buckwheat and Rosa laevigata Michx have been used to reduce oxidative stress damage to various organs during IR.

Caffeine modulates apoptosis, oxidative stress, and inflammation damage induced by tramadol in cerebellum of male rats.

Tramadol, an opioid used as analgesic, can induce neurotoxic effects associated to cognitive dysfunction. Moreover, caffeine has been reported to have neuroprotective effects. In this regard, we hypothesized that administration of caffeine can modulate tramadol-induced damages in cerebellum. For this study, forty male Wistar rats were divided into four groups: the control group, the tramadol group (50 mg/kg), the caffeine group (37.5 mg/kg), and the tramadol+caffeine group (50 mg/kg tramadol+37.5 mg/kg caffeine). At the end of study (day 21), after performing rotarod behavioral test, cerebellum tissue samples were removed and prepared for further evaluations including biochemical profile markers (MDA, GPx, and SOD), immunohistochemistry for Caspase-3, as well as the expression of genes involved in cellular processes such as inflammation markers (IL-1ß, HMGB1, IL-6, and TNF), apoptosis markers (Caspase-3, Caspase-8, Bax, and P21), and autophagy markers (LAMP2, ATG5, BECN1, and ATG12). Stereological evaluations were performed to determine the total volume of granular and molecular layers and white matter of cerebellum tissue and numerical density of the Purkinje cells. Our results showed that the stereological parameters, biochemical profiles (except MDA) and behavioral function were significantly higher in the tramadol+caffeine group compared to the tramadol group. Autophagy-related genes were significantly upregulated in tramadol+caffeine group compared to the tramadol group. While the expression of inflammatory and apoptosis genes, MDA level, as well as density of apoptosis cells were significantly lower in the tramadol+caffeine group compared to the tramadol group. Briefly, it can be concluded that administration of caffeine has neuroprotective effects in cerebellar damages induced by tramadol.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

Long-term administration of high-dose methylphenidate-induced cerebellar morphology and function damage in adult rats.

BACKGROUND AND AIM: Stated in previous studies, physicians are typically prescribing methylphenidate (MPH), commonly known as Ritalin, for children diagnosed with attention deficit hyperactivity disorder (ADHD). Nevertheless, researchers have not still understood mechanisms of this stimulant medication. Research has also found an association between apoptosis signaling pathway, neurological disorder, as well as treatment targets for neurological diseases. Therefore, the present study investigated effects of 3-week Ritalin oral (20 mg/kg) administration versus vehicle therapy on cerebellar morphology and function in adult male rats. MATERIALS AND METHODS: A total number of 30 adult male rats were randomly but equally divided into control and treatment groups. In fact, the treatment group was administered by Ritalin at doses of 20 mg/kg for 21 days and the control group only received saline. At the end of weeks 1, 2, and 3 following drug treatment, rotarod performance test was fulfilled. Once the study ended, tissues of the cerebellum were separated; then, inflammation parameters (i.e. tumor necrosis factor [TNF- α] and interleukin 1 beta [IL-1ß]), pro-apoptotic genes (that is, bcl-2-associated X [bax] and caspase-8 proteins), along with histological changes were analyzed. RESULTS: According to the findings, Ritalin with the high dose of 20 mg/kg could remarkably enhance the levels of bax and caspase-8 genes compared with those in the control group (p < 0.05). It should be noted that treatment with Ritalin could significantly increase TNF-α and IL-1ß levels in isolated cerebellar cells (p < 0.05). Moreover, 20 mg/kg of Ritalin decreased mean volumes of granular layer, white matter, as well as molecular layers. It also reduced the number of Purkinje cells compared with those in control rats. In addition, lower coordination movement was observed in the group receiving Ritalin. CONCLUSION: Data analysis showed that chronic treatment with increased dose of Ritalin could possibly lead to neuroinflammation and neurodegeneration in the cerebellum of adult rats.

Effect of quercetin on the number of blastomeres, zona pellucida thickness, and hatching rate of mouse embryos exposed to actinomycin D: An experimental study.

BACKGROUND: Quercetin is a flavonoid with the ability to improve the growth of embryos in vitro, and actinomycin D is an inducer of apoptosis in embryonic cells. OBJECTIVE: The aim was to evaluate the effect of quercetin on the number of viable and apoptotic cells, the zona pellucida (ZP) thickness and the hatching rate of preimplantation embryos exposed to actinomycin D in mice. MATERIALS AND METHODS: Two-cell embryos were randomly divided into four groups (Control, Quercetin, actinomycin D, and Quercetin + actinomycin D group). Blastocysts percentage, hatched blastocysts, and ZP thickness of blastocysts was measured. The number of blastomeres was counted by Hoechst and propidium iodide staining and the apoptotic cells number was counted by TUNEL assay. RESULTS: The results showed that the use of quercetin significantly improved the growth of embryos compared to the control group (p=0.037). Moreover, quercetin reduced the destructive effects of actinomycin D on the growth of embryos significantly (p=0.026). CONCLUSION: quercetin may protect the embryos against actinomycin D so that increases the number of viable cells and decreases the number of apoptotic cells, which can help the expansion of the blastocysts, thinning of the ZP thickness and increasing the hatching rate in mouse embryos.