Silvane Souza Roman

Hepatoprotective effect of 3-alkynyl selenophene on acute liver injury induced by D-galactosamine and lipopolysaccharide.

The aim of this study was to investigate the hepatoprotective effect of 3-alkynyl selenophene (compound a), a selenophene compound, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in rats. The animals received compound a (25 and 50 mg/kg; per oral, p.o.) in the first day of treatment. In the second day, the rats received D-GalN (500 mg/kg; intraperitoneal, i.p.) and LPS (50 microg/kg; intraperitoneal, i.p.). Twenty-four hours after D-GalN/LPS administration animals were euthanized to the biochemical and histological analysis. Compound a (25 and 50 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by D-GalN/LPS. Compound a at 50 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by D-GalN/LPS. The inhibition of delta-aminolevulinic dehydratase (delta-ALA-D) activity and the decrease of ascorbic acid levels caused by D-GalN/LPS were protected by compound a (25 and 50 mg/kg). Glutathione S-transferase (GST) and catalase activities were not altered in all groups. The histological data showed that sections of liver from D-GalN/LPS-treated rats presented massive hemorrhage, the presence of inflammatory cells and necrosis. Compound a attenuated D-GalN/LPS-induced hepatic histopathological alterations. Based on the results, we demonstrated the hepatoprotective effect of compound a on acute liver injury induced by D-GalN/LPS.

Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice

The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.

Anticonvulsant effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole in a pilocarpine model in mice

AIM This study investigated the in vitro antioxidant activity of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), the anticonvulsant effect of BPD on seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and 4-aminopyridine (4-AMP) and the mechanism involved. METHODS BPD antioxidant activity in vitro was investigated using sodium nitroprusside (SNP) and malonate-induced thiobarbituric acid reactive species (TBARS) and sodium azide-induced reactive species (RS) production. Thiol peroxidase and oxidase as well as δ-aminolevulinate dehydratase (δ-ALA-D) activities were examined. Mice were pretreated via oral route (p.o.) with BPD (1-100 mg/kg) before intraperitoneal (i.p.) administration of PC (400 mg/kg), PTZ (80 mg/kg) or 4-AMP (12 mg/kg). To investigate the antioxidant effect of BPD on oxidative stress induced by PC, the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT) as well as the levels of RS and TBARS were determined in brains of mice. δ-ALA-D, acetylcholinesterase (AChE) and Na(+), K(+) ATPase activities were verified. KEY FINDINGS BPD (5 μM) reduced RS production and lipid peroxidation induced by SNP and malonate. BPD (1-50 μM) did not show thiol peroxidase and oxidase activities and did not alter δ-ALA-D activity. BPD (5 mg/kg) increased the latency to the seizure onset on PTZ and 4-AMP models. BPD (100 mg/kg) abolished seizures and death induced by PC in mice. BPD protected against the increase in RS and TBARS levels. The activity of Na(+), K(+) ATPase and AChE inhibited by PC remained unaltered in the BPD group. SIGNIFICANCE BPD showed anticonvulsant and antioxidant effects on seizures induced by PC in mice.

Lycopene treatment prevents hematological, reproductive and histopathological damage induced by acute zearalenone administration in male Swiss mice

Zearalenone (ZEA) is a mycotoxin commonly found as a contaminant in cereals. ZEA toxicity targets mainly the reproductive system, and oxidative stress plays an etiological role in its toxic effects. Therefore, the present study aimed to investigate the effect of lycopene, a potent carotenoid antioxidant, on markers of oxidative stress in liver, kidney and testes, and on reproductive, hematological and histopathological parameters after ZEA administration. Adult Swiss albino male mice received lycopene (20mg/kg, p.o.) for ten days before a single oral administration of ZEA (40mg/kg, p.o.), and 48h thereafter tissues (liver, kidney, testes and blood) were collected for biochemical, hematological and histological analyses. Lycopene prevented ZEA-induced changes in hematological parameters (increased number of leukocytes, segmented neutrophils, sticks, eosinophils and monocytes and decreased number of red blood cells (RBC), number of lymphocytes and platelets). Moreover, lycopene prevented the reduction in the number and motility of spermatozoa and the testicular tissue damage induced by ZEA. In addition, lycopene prevented the decrease in glutathione-S-transferase activity in kidney and testes and increased glutathione-S-transferase activity per se in the liver, kidneys and testes as well as superoxide dismutase activity in the liver. In summary, lycopene was able to prevent ZEA-induced acute toxic effects in male mice, suggesting that this antioxidant carotenoid may represent a promising prophylactic strategy against ZEA toxicity.

Involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide on testicular damage induced by cadmium in mice.

The involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide (PhSe)(2) on testicular damage caused by cadmium in mice was investigated. Mice received a single dose of CdCl(2) (5mg/kg, intraperitoneally). Thirty minutes after the CdCl(2) injection, they received a single oral dose of (PhSe)(2) (400micromol/kg). Twenty-four hours after CdCl(2) administration, blood samples were collected and mice were killed and had their testes dissected. Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and lactato dehydrogenase (LDH) activities as well as creatinine levels) were determined. The activity of delta-aminolevulinate dehydratase (delta-ALA-D), the levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and nonprotein thiols (NPSH) and histological analysis were determined in collected samples. Results demonstrated that (PhSe)(2) protected against toxicity induced by CdCl(2) on delta-ALA-D activity, ascorbic acid and NPSH levels. (PhSe)(2) protected against the increase in plasma AST, ALT and LDH activities caused by CdCl(2). Testes of mice exposed to CdCl(2) showed marked histopathological alterations that were ameliorated by administration of (PhSe)(2). (PhSe)(2) protected against toxicity induced by CdCl(2) in testes of mice. Ascorbic acid and NPSH, non-enzymatic antioxidant defenses, are involved in the protective effect of (PhSe)(2) against testicular damage caused by CdCl(2) in mice.

Involvement of catalase in the protective effect of binaphthyl diselenide against renal damage induced by glycerol

In the present study, the protective effect of binapthyl diselenide [(NapSe)(2)] was investigated on glycerol-induced renal damage in rats. Adult male Wistar rats were treated with (NapSe)(2) (50 mg/kg, orally) or vehicle. After 24 h (NapSe)(2) treatment, the animals received an intramuscular injection of glycerol (8 ml/kg, dissolved in saline) or vehicle as a divided dose into the hind limbs. Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Non-protein thiol (NPSH) levels and catalase (CAT) activity were evaluated in renal homogenates. Histopathological evaluations were also performed in kidneys of rats. The rats exposed to glycerol presented swelling of the proximal and distal tubules with evidence of cell damage and death. Glycerol-exposed rats presented an increase in renal failure markers (plasmatic urea and creatinine levels) and a reduction in renal CAT activity. No change was observed in NPSH levels in kidneys of rats exposed to glycerol. (NapSe)(2) protected against the alterations caused by glycerol in rats. (NapSe)(2) increased per se NPSH levels (33%) in kidneys of rats. In conclusion, the results demonstrated that treatment with (NapSe)(2) protected against renal damage induced by glycerol in rats, probably due to its antioxidant effect.

Diphenyl diselenide prevents hepatic alterations induced by paraquat in rats.

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.

The peroxisome proliferator‐activated receptor‐γ agonist pioglitazone protects against cisplatin‐induced renal damage in mice

Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non‐diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR‐γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg–1). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg–1 day–1, per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non‐enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S‐transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin‐induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR‐γ agonists in human application for protecting against drugs‐induced nephrotoxicity. Copyright

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti-inflammatory mechanisms

Propolis has been highlighted for its antioxidant, anti‐inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV‐2) in female BALB/c mice. The treatment was divided in 5 days of pre‐treatment with HPE [50 mg·kg–1, once a day, intragastric (i.g.)], HSV‐2 infection [10 µl of a solution 1 × 102 plaque‐forming unit (PFU·ml–1 HSV‐2), intravaginal inoculation at day 6] and post‐treatment with HPE (50 mg·kg–1) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non‐protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV‐2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV‐2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti‐inflammatory properties. Copyright

Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice.

Chrysin is a flavonoid which is found in bee propolis, honey and various plants. Antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. Conversely, neurochemical factors associated with this effect require further investigations. Thus, we investigated the possible involvement of pro-inflammatory cytokines, kynurenine pathway (KP), 5-hydroxytryptamine (5-HT) metabolism and caspases activities in the effect of chrysin in mice exposed to unpredictable chronic stress (UCS). UCS applied for 28 days induced a depressive-like behavior, characterized by decrease in the time of grooming in the splash test and by increase in the immobility time in the tail suspension test. Oral treatment with chrysin (5 or 20mg/kg, 28 days), similarly to fluoxetine (10mg/kg, positive control), culminated in the prevention of these alterations. UCS elevated plasma levels of corticotropin-releasing hormone and adrenocorticotropic hormone, as well the tumor necrosis factor-α, interleukin-1β, interleukin-6 and kynurenine levels in the prefrontal cortex (PFC) and hippocampus (HP). UCS induced the decrease in the 5-HT levels in the HP and the increase in the indoleamine-2,3-dioxygenase, caspase 3 and 9 activities in the PFC and HP. Treatment with chrysin, similarly to fluoxetine, promoted the attenuation of these alterations occasioned by UCS. These results corroborated with the antidepressant potential of chrysin in the treatment of psychiatric diseases. Furthermore, this work indicated the association of pro-inflammatory cytokines synthesis, KP, 5-HT metabolism and caspases activities with the action exercised by chrysin in mice exposed to UCS.