Natasha Frasson Pavin

Antinociceptive and anti-hypernociceptive effects of Se-phenyl thiazolidine-4-carboselenoate in mice

In this study, the antinociceptive, anti-hypernociceptive and toxic effects of orally administered (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC, 1-50 mg/kg) were evaluated in mice. Se-PTC did not change plasma aspartate (AST) and alanine aminotransferase (ALT) activities or urea and creatinine levels. Furthermore, in an open field test, Se-PTC did not alter the number of crossings and rearing. Se-PTC significantly reduced the amount of writhing when assessed by acetic acid-induced visceral nociception and attenuated the licking time of the injected paw in the early and late phases of a formalin test. In addition, Se-PTC reduced nociception produced by intra-plantar (i.pl.) injection of glutamate, capsaicin, cinnalmaldehyde, bradykinin, phorbol myristate acetate and 8-Bromo-cAMP. Se-PTC caused a significant increase in hot plate and tail-immersion response latencies, but the antinociceptive effect of Se-PTC in the tail immersion was not abolished by pretreatment with the non-selective opioid receptor antagonist, naloxone. Se-PTC (25 mg/kg) significantly inhibited nociceptive behavior induced by intrathecal (i.t.) injection of glutamate, N-methyl-D-aspartate (NMDA) and (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), but failed to affect nociception induced by kainate and α-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA). Mechanical hypernociception induced by carrageenan and Complete Freunds Adjuvant was attenuated by Se-PTC administration. These results indicate that Se-PTC produces antinociception in several models of nociception.

Antinociceptive and anti-hyperalgesic effects of bis(4-methylbenzoyl) diselenide in mice: Evidence for the mechanism of action

Abstract Context: The organoselenium compounds have been described to demonstrate several biological activities, including pain management. Objective: This study investigated the antinociceptive, hyperalgesic, and toxic effects of oral administration of bis(4-methylbenzoyl) diselenide (BMD) in mice. Materials and methods: The antinociceptive and anti-hyperalgesic effects of BMD (1, 5, 10, 25, and 50 mg/kg, p.o.) were evaluated using models of nociception: formalin, capsaicin, bradykinin (BK), cinnamaldehyde, phorbol myristate acetate (PMA), 8-bromo-cAM, and glutamate-induced nociception; and mechanical hyperalgesia induced by carrageenan (Cg) or complete Freunds adjuvant (CFA). The acute toxicity was evaluated by biochemical markers for hepatic and renal damages. Results: BMD significantly inhibited the licking time of the injected paw in the early and late phases of a formalin test with ED50 values of 14.2 and 10.8 mg/kg, respectively. This compound reduced nociception produced by capsaicin (ED50 of 32.5 mg/kg), BK (ED50 of 24.6 mg/kg), glutamate (ED50 of 28.7 mg/kg), cinnamaldehyde (ED50 of 18.9 mg/kg), PMA (ED50 of 9.6 mg/kg), and 8-bromo-cAMP (ED50 of 24.8 mg/kg). In the glutamate test, the pretreatment with nitric oxide (NO) precursor, l-arginine, reversed antinociception caused by BMD or Nω-nitro-l-arginine (L-NOARG), but the effect of BMD was not abolished by naloxone. Mechanical hyperalgesia induced by Cg and CFA was attenuated by BMD, 70 ± 4% and 65 ± 4%, respectively. Furthermore, a single oral dose of BMD did not change plasma aspartate (AST) and alanine aminotransferase (ALT) activities or urea and creatinine levels. Conclusion: BMD demonstrated as a promising compound because of the antinociceptive and anti-hyperalgesic properties in mice.

Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

Alzheimers disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5 mg/kg) or vehicle (canola oil) was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

Comparative effect of Camellia sinensis teas on object recognition test deficit and metabolic changes induced by cafeteria diet

Objectives: Consumption of high-fat and high-sugar diets in Western countries has increased significantly causing major global health problems including metabolic syndrome and obesity. In addition, studies have suggested that obesity can lead to learning and memory deficits. In this context, the use of natural compounds with low costs, minor side effects and increased antioxidant activity, such as teas, could reduce the damages induced by obesity. We investigated the effect of white, green, red, and black teas (Camellia sinensis) and their possible neuroprotective mechanisms in an experimental obesity model induced by a cafeteria diet (CD). Methods: Female Swiss mice (20–30 g) were used; they received a normal diet or a hypercaloric diet (CD) during 8 weeks. Concomitantly, some mice received orally white, green, red, or black teas (1% dose) or water. Results: The mice subjected to CD showed weight gain, body fat accumulation, increased glucose, cholesterol, and triglycerides, associated to recognition memory deficits and increased reactive species (RS) levels and acetylcholinesterase (AChE) activity in the hippocampus. All teas significantly reduced AChE activity and partially reduced fat accumulation. Green and red teas reduced memory deficit. White, green, and black teas reduced RS levels, while only green and black tea reduced plasma triglyceride levels. Discussion: According to the results obtained it is possible to conclude that green tea was better than other teas in reducing effects of the CD model, being able to protect a greater number of parameters.

Selenofuranoside improves long-term memory deficits in rats after exposure to monosodium glutamate: Involvement of Na+, K+-ATPase activity

Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects of this additive, including functional, learning, and behavioral alterations, have been observed in experimental animals and humans. Studies have shown learning and memory impairment in adult animals exposed to MSG. However, studies relating exposure to MSG to acetylcholinesterase (AChE) and Na+, K+-ATPase activities and memory damage are still scarce in the literature. The aim of the present study was to assess the possible protective effects of selenofuranoside, an organoselenium compound, against the impairment of long-term memory, Na+, K+-ATPase and AChE activities, and oxidative stress after MSG exposure in rats. MSG (2g/kg) and/or selenofuranoside (5mg/kg) were administered orally to 5-week-old male Wistar rats for 10days. On the 10th day, after the administration of last dose of the drug(s), the rats were subjected to behavioral tests: the open-field test and step-down passive avoidance task (SDPA). The blood, liver, kidney, cortex, and hippocampus were removed to determine the oxidative stress parameters, such as the levels of reactive species, lipid peroxidation, antioxidant enzyme activities, and endogenous nonenzymatic antioxidant content. Furthermore, the cortex and hippocampus were used to determine the Na+, K+-ATPase and AChE activities. The results demonstrate that the administration of MSG led to long-term memory impairment, as shown in the SDPA task, and also hippocampal and cortical Na+, K+-ATPase inhibition. There were no alterations in the AChE activity and oxidative stress parameters. Treatment with selenofuranoside attenuated memory impairment associated with MSG exposure by improving the hippocampal Na+, K+-ATPase activity.

Tribulus terrestris Protects against Male Reproductive Damage Induced by Cyclophosphamide in Mice

Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 β-HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.