The brown algae: Sargassum binderi sonder bears potential nephroprotective activity in in-vivo experimental model.

OBJECTIVES: This study aimed to investigate the protective activity of brown seaweed, the ethanolic and water extracts of Sargassum binderi (S. binderi) were examined. Anticancer drug, cisplatin is normally used for the treatment of solid tumors that cause acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute nephrotoxicity study, animals were divided into several groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The S. bindari ethanolic and water extract were given orally in a dose of 200mg/kg for 5days. Various biomarkers were assessed to observe the nephroprotective potential, while antioxidant activities were investigated using reduced glutathione, catalase and malondialdehyde as oxidative stress. GCMS was performed to validate the presence of important therapeutic moieties. RESULTS: The current result justified that pretreatment with S. binderi inhibited the elevation of antioxidant parameters and also showed protection against lipid peroxidation, induced by cisplatin challenge. The overall impact was the nephroprotection, which has been revealed from the results. GCMS evaluation of hexanes fraction revealed the presence of therapeutically important compounds including heptasiloxane, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecamethyl, cyclooctasiloxane, and hexadecamethyl. These compounds have been reported for their antioxidant, antibacterial, anticancer, and antifungal activities. CONCLUSION: S. binderi showed reno-protective effect by checking their well-known biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

Antioxidant and anti-arthritic activity of Bombax buonopozense P. Beauv. leaves.

BACKGROUND AND AIM: Bombax buonopozense (Bombacaceae) leaves have been used traditionally for arthritis in south-western Nigeria. Therefore, the aim of the study was to investigate the antioxidant and anti-arthritic activity of B. buonopozense in Complete Freund adjuvant-induce arthritic wistar rats. EXPERIMENTAL PROCEDURE: The plant leaves methanol extract and fractions were screened for preliminary phytochemicals and brine shrimp lethality was determined. Total phenolic content (TPC), Total flavonoid content (TFC) as well as anti-oxidant activity of the extract and fractions were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Cyclophosphamide, gallic acid, and ascorbic acid were used as standards respectively. Anti-arthritic activity of crude methanol extract (BBME) at 100, 200 and 400mg/kg was evaluated in complete Freund's adjuvant (CFA) induced arthritis model in rats. Data were analysed using Graph pad prism version 5, two-way and one-way ANOVA, and Bonferroni post hoc test. RESULTS AND CONCLUSION: Phytochemical screening revealed the presence of flavonoids, alkaloids, and phenolics. The brine shrimp lethality assay of the crude extract and fractions gave LC50 value≥1000µg/mL, compared to Cyclophosphamide (LC50=224.7±0.35µg/mL). The BBME had TPC value of 19.8±0.56mg GAE/g, while the TFC of ethyl acetate fraction was the highest (173.5±0.05mg QE/g). The ethyl acetate fraction has the highest antioxidant activity (IC50=20.96±0.23µg/mL) as compared to ascorbic acid (2.8±0.01) and rutin (20.6±9.26µg/mL). BBME significantly reduced the paw circumference. BBME (400mg/kg) prevented biochemical changes to a greater extent than Celecoxib (20mg/kg). Bombax buonopozense leaves could be an effective antiarthritic and holds prospect in the treatment of rheumatoid arthritis.

Anthocyanins: Potential phytochemical candidates for the amelioration of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is described by too much hepatic fat deposition causing steatosis, which further develops into nonalcoholic steatohepatitis (NASH), defined by necroinflammation and fibrosis, progressing further to hepatic cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD is linked to different aspects of the metabolic syndrome like obesity, insulin resistance, hypertension, and dyslipidemia, and its pathogenesis involves several elements including diet, obesity, disruption of lipid homeostasis, and a high buildup of triglycerides and other lipids in liver cells. It is therefore linked to an increase in the susceptibility to developing diabetes mellitus and cardiovascular diseases. Several interventions exist regarding its management, but the availability of natural sources through diet will be a benefit in dealing with the disorder due to the immensely growing dependence of the population worldwide on natural sources owing to their ability to treat the root cause of the disease. Anthocyanins (ACNs) are naturally occurring polyphenolic pigments that exist in the form of glycosides, which are the glucosides of anthocyanidins and are produced from flavonoids via the phenyl propanoid pathway. To understand their mode of action in NAFLD and their therapeutic potential, the literature on in vitro, in vivo, and clinical trials on naturally occurring ACN-rich sources was exhaustively reviewed. It was concluded that ACNs show their potential in the treatment of NAFLD through their antioxidant properties and their efficacy to control lipid metabolism, glucose homeostasis, transcription factors, and inflammation. This led to the conclusion that ACNs possess efficacy in the amelioration of NAFLD and the various features associated with it. However, additional clinical trials are required to justify the potential of ACNs in NAFLD.

Antioxidant and cytotoxicity activity of a nanoemulsion from Satureja kermanica (Lamiaceae).

OBJECTIVE: Satureja kermanica is a native species with a relatively wide distribution in Iran, which has been studied less. Due to the low stability of the plants, in this study, the methanolic extract of S. kermanica (MSK) along with a nanoemulsion (NEK) preparation was evaluated in terms of antioxidant and cytotoxic activity. MATERIAL AND METHODS: The aerial parts of S. kermanica were collected and after studying the organoleptic characteristics and quality control parameters, were extracted with methanol. Total phenolic compounds and total flavonoids of the plant were measured. A nanoemulsion preparation was prepared using ultrasonication method from S. kermanica extract. After measuring the particle size of nanoemulsion, both MSK and NEK were evaluated for their antioxidant and cytotoxic activity using DPPH scavenging assay and MTT colorimetric method on breast cancer cell line (MCF-7) respectively. RESULTS: Phytochemical studies exhibited the presence of secondary metabolites including flavonoids, tannins, steroids and carbohydrates in the plant. Based on the histogram of the SBL nanosizer, the average diameter of nanoemulsion was determined as 37.09nm. Both MSK and NEK showed dose-dependent antioxidant and cytotoxic activity. The IC50 value of MSK and NEK for DPPH inhibition was 30.105±2.781 58.14±0.84µg/mL and for toxicity toward MCF-7 cell line was 1251.088 and 201.745±4.554µg/mL respectively. CONCLUSION: MSK and NEK showed antioxidant and cytotoxic activity, but in NEK, the antioxidant and cytotoxic potential of the plant was more prominent, which may be due to the rapid release of the bioactive component from the nanoemulsion.

The influence of harvest time on total phenolic and flavonoid contents, antioxidant, antibacterial and cytotoxicity of Rheum khorasanicum root extract.

INTRODUCTION: For many centuries, medicinal herbs and their derivatives have been used to treat or prevent various diseases. However, environmental factors such as the season for collection of plant may change the therapeutic efficacy. The present work investigates seasonal variations of phenolic, flavonoid content, antioxidant, antibacterial, and cytotoxic potential of hydroalcoholic extract of Rheum khorasanicum (HER). METHODS: R. khorasanicum was collected in three different months: December, February, and April. The Folin-Ciocalteu assay was applied to measure the total phenolic content of HER. Antioxidant activities (DPPH and FRAP) were also determined. Next, the extracts were evaluated for antibacterial potential against some Gram-positive and Gram-negative strains. The minimal inhibitory concentration (MIC) was determined by the microdilution method. Finally, the effect of extracts on the viability of C6, A549, and HT-29 cells was evaluated via the MTT assay. RESULTS: All three extracts contained considerable phenolic and flavonoid contents and showed desirable antioxidant activity. The April sample exhibited the greatest phenolic and flavonoid content and significant antioxidant activity potential in the FRAP test. In addition, the April sample had the highest antibacterial activity and cytotoxic effect on the cancerous cell lines. CONCLUSION: The April extract showed more antioxidant, antibacterial and cytotoxic effect, probably because of its higher phenolic and flavonoid contents than other samples. These results demonstrate that the harvest timing of R. khorasanicum affects the plant's phenolic content and its antioxidant and cytotoxicity activities.

Cadmium chloride generates cytotoxic reactive species that cause oxidative damage and morphological changes in human erythrocytes.

Cadmium chloride (CdCl2) is a widely used industrial compound that exhibits multiple organ toxicity. Cadmium is transported through blood where erythrocytes are exposed to its action. Here the effect of CdCl2 on human erythrocytes was examined under in vitro conditions. Human erythrocytes were treated with 0.01-0.5 mM CdCl2 for 24 h at 37 °C. Lysates were made from CdCl2 treated and untreated (control) cells and used for further analysis. CdCl2 treatment resulted in marked hemolysis of erythrocytes and oxidation of hemoglobin to methemoglobin. This will result in anemia and also reduce the oxygen carrying ability of erythrocytes. Hemoglobin oxidation was accompanied by degradation of heme and release of free ferrous iron moiety. Further analysis showed elevated lipid hydroperoxides and formation of advanced oxidation protein products along with reduction in total sulfhydryl content, indicating the generation of oxidative stress condition in the cell. Incubation of erythrocytes with CdCl2 enhanced generation of reactive oxygen and nitrogen species, decreased the antioxidant power and inhibited pathways of glucose metabolism. Plasma membrane was damaged as indicated by enhanced osmotic fragility and inhibition of membrane bound enzymes. This was confirmed by electron microscopy which showed formation of echinocytes. These results show that CdCl2 generates reactive species which impair the antioxidant system resulting in oxidative damage to erythrocytes.

Attenuation of Hg(II)-induced cellular and DNA damage in human blood cells by uric acid.

Mercury (Hg) is a widespread environmental pollutant and toxicant that induces multiple organ damage in humans and animals. Hg toxicity is mediated by the induction of oxidative stress in the target cells. We used uric acid (UA), a potent antioxidant found in biological fluids, to protect human red blood cells (RBC) and lymphocytes against Hg-mediated cell, organelle, and genotoxicity. RBCs were incubated with mercuric chloride (HgCl2), an Hg(II) compound, either alone or in the presence of UA. Incubation of RBCs with only HgCl2 increased the production of nitrogen and oxygen radical species, enhanced methemoglobin levels, heme degradation, free ferrous iron, oxidation of proteins and membrane lipids, and reduced the antioxidant capacity of cells. UA enhanced the antioxidant capacity of RBCs and restored metabolic, plasma membrane-bound, and antioxidant enzyme activities. Scanning electron microscopy showed that UA prevented HgCl2-mediated morphological changes in RBCs. HgCl2 dissipated the mitochondrial membrane potential and increased lysosomal membrane damage in lymphocytes, but UA pre-treatment attenuated these effects. Genotoxicity analysis by comet assay showed that UA protected lymphocyte DNA from HgCl2-induced damage. Importantly, UA itself did not exhibit any deleterious effects on RBCs or lymphocytes. Thus, UA protects human blood cells from Hg(II)-mediated oxidative damage, reducing the harmful effects of this extremely toxic metal. We suggest that UA has a similar protective role in plasma against heavy metal toxicity.

p-Chloro-diphenyl diselenide modulates Nrf2/Keap1 signaling and counteracts renal oxidative stress in mice exposed to repeated dexamethasone administrations.

Dexamethasone is a synthetic glucocorticoid that has been associated with oxidative stress in central and peripheral tissues. p-Chloro-diphenyl diselenide ((p-ClPhSe)2) is an antioxidant organoselenium compound. The present study evaluated whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1) signaling contributes to the (p-ClPhSe)2 antioxidant effects in the kidney of mice exposed to dexamethasone. Adult Swiss mice received dexamethasone (intraperitoneal) at a dose of 2 mg/kg or its vehicle for 21 days. After that, mice were treated with (p-ClPhSe)2 (intragastric) (1, 5, or 10 mg/kg) for 7 days. Samples of kidneys were collected for biochemical assays. (p-ClPhSe)2 at a dose of 1 mg/kg reversed the renal reactive oxygen species (ROS) and carbonyl protein (CP) levels increased by dexamethasone. (p-ClPhSe)2 at doses of 5 and 10 mg/kg was effective against the increase of thiobarbituric acid reactive substances, ROS, and CP, as well as the decrease of δ-aminolevulinic acid dehydratase activity and nonprotein sulfhydryl levels induced by dexamethasone. At 5 mg/kg, (p-ClPhSe)2 reduced the renal levels of 4-OH-2-HNE and heme oxygenase (HO-1), as well as modulated the Nrf2/Keap-1 signaling in mice exposed to dexamethasone. The present findings revealed that (p-ClPhSe)2 antioxidant effects were associated with the modulation of Nrf2/Keap-1 signaling pathway in the kidney of mice exposed to dexamethasone.

Anticonvulsant activity of oxaprozin in a rat model of pentylenetetrazole-induced seizure by targeting oxidative stress and SIRT1/PGC1α signaling.

The effect of oxaprozin (OXP) on an experimental model of seizures in rats was investigated in this study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg). The anticonvulsant effect of OXP (100, 200, and 400 mg/kg, intraperitoneally) was evaluated in a seizure model. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for antioxidant assays (nitric oxide (NO) and glutathione (GSH)). The animals' brains were also isolated to gauge the relative expression of genes in the oxidative stress pathway (sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)). Intraperitoneal injection of OXP increased the mean latency of myoclonic jerks and generalized tonic-clonic seizure (GTCS) and decreased the number of myoclonic jerks and GTCS duration compared with the PTZ group. Biochemical tests showed that pretreatment with OXP was able to restore GSH serum levels and reverse the augmented NO serum levels caused by PTZ induction to the normal level. The quantitative polymerase chain reaction results also revealed that OXP counteracts the negative effects of PTZ by affecting the expression of the Sirt1 and Pgc1α genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal, anti-inflammatory OXP drug in a model of neural impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

The herbicide paraquat alters growth and melanin production on the Cryptococcus neoformans/Cryptococcus gattii species complex.

Paraquat (1,10-dimethyl-4,4-bipyridinium dichloride; PQ) is a free-radical producing herbicide that affects cell membranes and can upset the environmental balance of microorganisms present in soil, such as Cryptococcus spp. This study aimed to evaluate the in vitro activity of PQ against Cryptococcus spp. in planktonic and biofilm forms, as well as the protective effect of antioxidant agents against the antifungal effect of PQ and the kinetics of melanin production in response to PQ. Susceptibility to PQ was evaluated by microdilution. Cryptococcus sp. strains exposed to PQ were grown in media with ascorbic acid (AA) and glutathione (GSH). Melanin production was assessed in the presence of l-3,4-dihydroxyphenylalanine (l-DOPA) + PQ. The minimum inhibitory concentration of PQ against Cryptococcus spp. ranged from 8 to 256 µg/mL. Furthermore, PQ reduced biofilm formation. AA and GSH restored the fungal growth of Cryptococcus spp. exposed to PQ. In addition, l-DOPA + PQ delayed melanin production by 24 and 48 h for C. deuterogattii and C. neoformans sensu lato, respectively, suggesting that PQ induces a fitness trade-off in melanin production. Taken together, our data suggest that the antifungal effect of PQ against Cryptococcus spp. possibly exerts selective pressures interfering with biofilm formation and melanin production by these yeasts.

Antiparkinsonian activity of Tabebuia impetiginosa bark and biochemical analysis of dopamine in rat brain homogenates.

OBJECTIVES: Improving economy and well-being in developing nations like India has expanded life expectancy and changed the attention from transmittable to non transmittable diseases such as Parkinson's disease. Tabebuia impetiginosa has been utilized by cultivators as a general tonic, immunostimulant, adaptogen and also in motor disorders. The present investigation was to explore the antiparkinsonian activity of Tabebuia impetiginosa bark by experimental methods. MATERIALS AND METHODS: Control group-I was served with distilled water. Group-II was considered as pathological control [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 2mg/nostrils i.n, Reserpine 40mg/kg s.c, Haloperidol 0.5mg/kg, i.p]. Group-III served with standard drug (Apomorphine 40mg/kg, s.c). Group IV and V received aqueous extract of Tabebuia impetiginosa bark in doses of 300 and 500mg/kg/day respectively. Tremor, hypokinesia, muscular rigidity, catatonia, postural immobility, postural instability and catalepsy were assessed for antiparkinsonian activity. RESULTS: The bark extract served group exhibited the increased levels of dopamine (5700±1.84ng/g) when compared to control groups (4300±3.17ng/g). The extract at both the doses displayed a significant reduction in postural flexion, moderate decrease in tremor, muscular rigidity and postural immobility scores but do not exhibit significant lowering of hypokinesia score in reserpine induced Parkinsonian model. The reduction in catatonia and catalepsy scores is more remarkable in case of high dose of extract (500mg/kg) compared to standard drug in Neuroleptic induced Parkinsonism. CONCLUSION: The findings demonstrate that Tabebuia impetiginosa bark extract has significant anti-cataleptic potentials and the antioxidant effect of the bark may also be a significant contributor to its antiparkinsonian activity.

Evaluation of antioxidant potential of Heliotropium bacciferum Forssk extract and wound healing activity of its topical formulation in rat.

Wound healing is a dynamic process that occurs in the tissue under the skin. During this process, oxidative stress biomarkers are excessively produced, which finally lead to inflammation and cellular damage. In this study, efforts have been made to evaluate the antioxidant effect and wound healing activity topical formulation containing Heliotropium bacciferum Forssk extract. The in vitro antioxidant properties were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities and the ferric reducing antioxidant power (FRAP) assay. The herbal ointments (2.5% w/w and 5% w/w) were prepared from the hydroalcoholic extract of H. bacciferum Forssk and administrated on the induced wounds in Wistar rats. The chromatic assay, percentage of wound contraction, and histopathological studies were used for evaluating the wound healing activity. For the evaluation of reactive oxygen species (ROS), catalase (CAT) activity, superoxide dismutase (SOD), and glutathione (GSH) levels were examined. The DPPH method showed tremendous radical scavenging activities at the corresponding concentrations with EC50 value of 80µg/mL. Topical application of the ointment (5% w/w) showed the highest wound contraction in comparison to the positive control (treated with CICALFATE™) and the control group (treated with normal saline). Similarly, the histological study of the group treated with the extract ointment (5% w/w) showed full collagen tissue deposition with a complete epidermal regeneration. The results of the assessment of GSH levels as well as CAT and SOD activities in the treated group (5% w/w) confirmed the scavenging property of the extract ointment. Our findings indicated the proper wound healing impact of the topical formulation of H. bacciferum Forssk due to its notable antioxidant capacity.

L-ergothioneine and metformin alleviates liver injury in experimental type-2 diabetic rats via reduction of oxidative stress, inflammation, and hypertriglyceridemia.

Type-2 diabetes (T2D) is associated with liver toxicity. L-ergothioneine (L-egt) has been reported to reduce toxicity in tissues exposed to injury, while metformin is commonly prescribed to manage T2D. Hence, this study evaluates the hepatoprotective role of L-egt, with or without metformin, in T2D male rats. A total of 36 adult male Sprague-Dawley rats were randomly divided into non-diabetic (n = 12) and diabetic (n = 24) groups. After induction of diabetes, animals were divided into six groups (n = 6) and treated orally either with deionized water, L-egt (35 mg/kg bodyweight (bwt)), metformin (500 mg/kg bwt), or a combination of L-egt and metformin for 7 weeks. Body weight and blood glucose were monitored during the experiment. Thereafter, animals were euthanized and liver tissue was excised for biochemical, ELISA, real-time quantitative PCR, and histopathological analysis. L-egt with or without metformin reduced liver hypertrophy, liver injury, triglycerides, oxidative stress, and inflammation. Also, L-egt normalized mRNA expression of SREBP-1c, fatty acid synthase, nuclear factor kappa B, transforming growth factor ß1, nuclear factor erythroid 2-related factor 2, and sirtuin-1 in diabetic rats. Furthermore, co-administration of L-egt with metformin to diabetic rats reduced blood glucose and insulin resistance. These results provide support to the therapeutic benefits of L-egt in the management of liver complications associated with T2D.

Role of 7-chloro-4-(phenylselanyl) quinoline in the treatment of oxaliplatin-induced hepatic toxicity in mice.

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg-1) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg-1) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

Toxicity of Mangifera Indica aqueous stem bark extract evaluated in drosophila melanogaster used as model organism.

BACKGROUND: Mangifera indica has been used for treating health complications with little data on its toxicological impact on survival, geotaxis, reproduction, and the antioxidant system. METHODS: Total phenol and flavonoid contents were estimated. The ingestion method of exposure (extract was mixed in flies' food) was used. Each concentration was administered per 10g fruit flies diet. 7-day LC50 was determined by exposing 50 flies for 7 days to Mangifera indica concentration ranging from 100mg extract/10g diet to 2000mg extract/10g diet. 28 days survival assay was performed by exposing 50 fruit flies each to 25mg extract/10g diet, 50mg extract/10 diet g, and 100mg extract/10g diet for 28 days. A 6-day short term exposure was also conducted to assess Mangifera indica toxic effect on climbing activity, survival, reproduction, and antioxidant system in Drosophila melanogaster. RESULTS: Total phenol and flavonoid content were 0.226±0.02 and 0.027±0.05mg/g dry weight of the extract, respectively. There was a significant mortality rate (P<0.05), and the 7-day LC50 was 353mg extract/10g diet. At 25mg extract/10g diet 50mg extract/10g diet and 100mg extract/10g diet, the survival-rate of fruit flies significantly dropped (P<0.05) with arise in Mangifera indica concentration. Short-term exposure also showed a significant reduction (P<0.05) in GST-activity, survival-rate, and emergence of young fruit flies with an increase in concentration. Total thiol, locomotor, AChE, and CAT activities decreased non-significantly (P>0.05). CONCLUSION: The significant adverse effect of Mangifera indica extract as seen in the decrease in survival rate, the emergence of young flies, climbing, and antioxidant activities of fruit flies suggests its cautious application and use in herbal medicine.

Therapeutic potential of selanyl amide derivatives in the in vitro anticholinesterase activity and in in vivo antiamnesic action.

The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of mice. In conclusion, the present study evidenced the in vitro anticholinesterase effect of two new selanyl amide derivatives in the cerebral structures of mice. Moreover, compound 1, a selanyl amide derivative containing a furan ring, demonstrated antiamnesic action due to its antioxidant and anticholinesterase activities in cerebral structures.

Evaluation of antioxidant activity and toxicity of sulfur- or selenium-containing 4-(arylchalcogenyl)-1H-pyrazoles.

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats.

Since cisplatin-induced nephrotoxicity has very important clinical consequences, the purpose of this study was to determine the potential protective effect of aminoguanidine on the acute kidney injury caused by cisplatin. Experiments were done on 40 Wistar rats divided into four groups. The CIS group received cisplatin in a single dose of 8 mg/kg, while the CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) by intraperitoneal injections. Animals in the AG group received only aminoguanidine (100 mg/kg) and those in the C group received saline. Quantitative evaluation of structural and functional alterations in the kidneys was performed by analysis of biochemical and parameters of oxidative stress and by histological and morphometric analysis of renal sections. Histological sections of kidney showed structural damage of proximal tubules and glomeruli that were induced by cisplatin. Morphometric analysis revealed statistically significant differences in the area of proximal tubules and the size and cellularity of glomeruli between the CIS and CISAG groups. Glomerular basement membrane thickness was increased in the CIS group, while aminoguanidine attenuated these changes in the CISAG group of rats. Our results suggest that aminoguanidine acts protectively and repairs structural and functional damage of kidney by engaging the existent antioxidative potential at the level of renal tissue.

In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model.

Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.

Haptoglobin phenotypes with weak antioxidant capacity increase risk factors of cardiovascular disease in Ghanaian HIV-infected patients on highly active antiretroviral therapy.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has considerably reduced HIV/AIDS-related morbidity and mortality; however, the therapy has been associated with the development of cardiovascular disease (CVD), and genetic predisposition factors may aggravate disease outcome. This study was aimed at investigating the relationship between haptoglobin phenotypes and risk factors of CVD in HIV patients. METHODS: A total of 105 HIV sero-positive patients on HAART and 75 HIV-infected HAART-naïve individuals were enrolled in the study. Socio-demographics and clinical characteristics of the participants were obtained using a well-structured questionnaire. Lipid profile, lactate dehydrogenase (LDH) and haptoglobin (Hp) phenotypes were analysed from serum whiles haemoglobin (Hb) level, CD4+ cell count and HIV viral RNA load were determined using whole blood. RESULTS: Atherogenic index of plasma (AIP) was significantly higher in patients on HAART than the naïve group (P < 0.05). Age, BMI, visceral fat, systolic blood pressure LDH and lipid variables strongly and positively correlated with AIP (P < 0.05), with the exception of HDL-c (P < 0.001) which showed a negative correlation. HAART was associated with hypertension (χ2  = 4.33, P = 0.037), hypercholesterolaemia (χ2  = 10.99, P < 0.001), elevated LDL-c (χ2 = 10.30, P < 0.001) and decreased HDL-c (χ2  = 3.87, P = 0.09). Hp2-2 and Hp0 collectively was strongly associated with hypertension (OR = 2.54, P = 0.011), obesity (OR = 5.97, P < 0.001) and hypercholesterolaemia (OR = 2.99, P < 0.001). CONCLUSION: HIV/AIDS patients on HAART expressing Hp phenotypes with weak antioxidant capacity have an increased risk of developing CVD.

OBJECTIF: La thérapie antirétrovirale hautement active (HAART) a considérablement réduit la morbidité et la mortalité liées au VIH/SIDA; cependant, le traitement a été associé au développement de maladie cardiovasculaire (MCV) et des facteurs de prédisposition génétique pourraient aggraver l'évolution de la maladie. Cette étude visait à étudier la relation entre les phénotypes de l'haptoglobine et les facteurs de risque de MCV chez les patients VIH. MÉTHODES: Un total de 105 patients VIH positifs sous HAART et 75 personnes infectés par le VIH mais naïfs au HAART ont été recrutés pour l'étude. Les caractéristiques sociodémographiques et cliniques des participants ont été obtenues à l'aide d'un questionnaire bien structuré. Le profil lipidique, les phénotypes de la lactate déshydrogénase (LDH) et de l' haptoglobine (Hp) ont été analysés à partir du sérum tandis que le taux d'hémoglobine (Hb), la numération des cellules CD4+ et la charge d'ARN viral du VIH ont été déterminés en utilisant du sang total. RÉSULTATS: L'indice athérogène du plasma (IAP) était significativement plus élevé chez les patients sous HAART que chez le groupe naïf (p <0,05). Les variables âge, IMC, graisse viscérale, tension artérielle systolique, LDH et lipides étaient fortement et positivement corrélées à l'IAP (p < 0,05), à l'exception du HDL-c (p < 0,001) qui présentait une corrélation négative. L'HAART a été associée à l'hypertension (χ2 = 4,33; p = 0,037), l'hypercholestérolémie (χ2 = 10,99; p <0,001), une LDL-c élevée (χ2 = 10,30; p <0,001) et une diminution de HDL-c (χ2 = 3,87; p = 0,09). Ensemble, Hp2-2 et Hp0 étaient fortement associés à l'hypertension (OR = 2,54; p = 0,011), à l'obésité (OR = 5,97; p <0,001) et à l'hypercholestérolémie (OR = 2,99; p <0,001). CONCLUSION: Les patients VIH/SIDA sous HAART exprimant des phénotypes Hp à faible capacité antioxydante ont un risque accru de développer une maladie cardiovasculaire.