Targeting Some Key Metalloproteinases by Nano-Naringenin and Amphora coffeaeformis as a Novel Strategy for Treatment of Osteoarthritis in Rats.

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups. Control, osteoarthritic (OA) (monosodium iodoacetate (MIA) 2 mg/50 µL saline, single intra-articular injection), OA+ indomethacin (2 mg/kg/daily/orally), OA+ nano-naringenin (25 mg/kg/daily/orally), and OA+ Amphora coffeaeformis (772 mg/kg/daily/orally). Treatments were initiated on the 8th day after osteoarthritis induction and continued for 28 days thereafter. Finally, blood and knee joint samples were collected from all rats for biochemical and histopathological evaluations. The current study showed that MIA induced oxidative stress, which resulted in changes in the inflammatory joint markers associated with increased right knee diameter and higher clinical scores for lameness. Amphora coffeaeformis followed by nano-naringenin exhibited a potential anti-arthritic activity by reducing the concentrations of serum MMP-3, ADAMTS-5, and joint MDA and increasing the levels of serum TIMP-3 and joint GSH, similar to indomethacin. The histopathological results confirmed these outcomes. In conclusion, Amphora coffeaeformis and nano-naringenin can be considered as natural therapeutic agents for osteoarthritis owing to their antioxidant and anti-inflammatory activities.

Thiol, volatile and semi-volatile compounds alleviate the stress of zinc oxide nanoparticles of the pomegranate callus.

Pomegranate trees are tropical and subtropical shrubs with nutritional benefits and pharmaceutical and therapeutic uses. Antioxidative systems protect the structure and function of cellular membranes. This study demonstrated the connection between oxidative stress generated by excess nanoparticles ZnO (ZnO-NPs) accumulation in pomegranate calli and the involvement of thiol groups and volatile and semi-volatile compounds in alleviating this stress. The effect of the non-enzymatic antioxidant system was studied using callus treated with three levels of ZnO-NPs or bulk particles (ZnO-BPs). With rising ZnO levels in the media, callus growth was gradually decreased by ZnO in both forms (NPs and BPs). Malondialdehyde (MDA) measurements revealed that different concentrations of both forms promoted lipid peroxidation. The supply of both forms had a considerable stimulatory influence on the cysteine (Cys) content in calli. Raised ZnO-NP concentrations increased glutathione (GSH) and non-protein thiols (NPTs) content in calli, but higher ZnO-BP concentrations lowered their content. Conversely, ZnO-NP levels reduced the protein thiols (PTs) content in calli, but ZnO-BP concentrations increased their content. GC-MS analysis was employed to investigate the volatile and semi-volatile chemical profiles within calli following exposure to 0 and 150 µg mL-1 of ZnO in both forms. GC-MS analysis detected 77, 67, and 83 compounds in ZnO-treated calli, of which 14, 16, and 20 with a similarity value greater than 70%, based on a NIST library, were recognized as metabolites for ZnO untreated and NPs- and BPs-treated calli, respectively. Six substances, including five alkanes and one morphinan, showed similarities in metabolite composition between control and NPs- or BPs-treated calli. ZnO-NPs-treated calli contained two alkane compounds only similar to the control, but ZnO-BPs-treated calli had six metabolites, including four alkanes, one carboxylic acid, and one ester. However, eight alkanes were similar within the callus treated with NPs and BPs.

Alleviating excess boron stress in tomato calli by applying benzoic acid to various biochemical strategies.

Benzoic acid (BA) represents vital roles in plant activity and response to diverse unfavorable conditions. However, its participation in mitigating excess boron (EB) stress in plants is elusive. Herein, we have examined the impacts of BA (1 µM) in controlling boron (B) uptake in tomato (Solanum lycopersicum L.) calli exposed to various EB levels (0, 1, 2, and 3 mM). The free, semi-bound, and bound B forms were stimulated by EB, while these forms were reduced in B-stressed calli by BA supplementation (40.37%, 36.08%, and 66.91%, respectively, less than 3 mM B-stressed calli alone). EB caused a reduction in the uptake of potassium (K+), calcium (Ca2+), magnesium (Mg2+), and nitrite (NO2-) while increasing the concentration of phosphorus (P), nitrate (NO3-), sulfur (S), and sulfate (SO42-) in B-stressed calli. BA application induced the uptake of K+, Ca2+, Mg2+, NO3-, S, and SO42-; however, it reduced P and NO2- concentrations in B-stressed calli. EB reduced nitrate reductase activity (NR), while BA application did not alleviate this reduction. EB treatments significantly, in most cases, increased sulfite oxidase (SO) activity. Supplementation of BA along with EB further enhanced SO activity. Cell wall components (cellulose, hemicellulose, and pectin) were decreased under EB treatments but considerably increased in B-stressed calli by BA application. Fourier Transform Infrared Spectrometer (FT-IR) output showed that EB treatments with/without BA led to alterations in cell wall functional groups of calli. Our findings indicated that BA application enabled tomato callus to counteract the harmful effect of EB, leading to improved callus growth.

Neuromodulatory effect of cinnamon oil on behavioural disturbance, CYP1A1, iNOStranscripts and neurochemical alterations induced by deltamethrin in rat brain.

The objective of this study was to investigate the influence of deltamethrin (DLM)on brain function and to find whether DLM-induced neurotoxicity is prevented by the treatment with cinnamon oil. Four groups of ten Wistar albino male rats each were used. Group I (control) received saline only. Group II received cinnamon oil alone at 0.5 mg/kg B.W. intraperitonally, whereas Group III received orally DLM alone at 6 mg/kg B.W. Groups IV was treated with cinnamon oil plus DLM for 21 days to induce neurotoxicity. Rat behaviour, brain acetylcholine esterase (AChE), serotonin, oxidative stress profile were assessed. Serum sampling for the assessment of corticosterone concentration was also carried out. Finally, we demonstrate the gene expression of CYP1A1 and iNOS and the histological picture of the brain. Considering the behaviour assessment, DLM administration alone caused neurobehavioral deficits manifested by anxiety-like behavior which represented ina marked decrease in the sleeping frequency and duration, and marked increase the digging frequency and a wake non-active behavior duration. Moreover, the open field result showed a significant decrease in central square entries and duration. The neurochemical analysis revealed that DLM significantly suppressed AChE activity and elevated serotonin and corticosterone concentrations. Furthermore, results revealed thatthe brain reduced glutathione (GSH) content, superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were significantly altered in DLM treated rats. Neurochemical disturbances were confirmed by histopathological changes in the brain. Furthermore, DLM up-regulates the mRNA expression of brain CYP1A1 and iNOS. Co-treatment with cinnamon oil exhibited significant improvement in behavioural performance and the brain antioxidant capacities with an increase in AChE activity and diminished the concentration of serotonin, serum corticosterone and MDA. Cinnamon oil treatment resulted in down-regulation of CYP1A1 and iNOS and improve the histologically picture. In conclusion, cinnamon oil ameliorated DLM-induced neurotoxicity through preventing oxidative stress-induced genotoxicity and apoptosis of brain in rats.

Comparative effects of zinc oxide and zinc oxide nanoparticle as feed additives on growth, feed choice test, tissue residues, and histopathological changes in broiler chickens.

Zinc is an essential nutritional trace mineral required for growth and health. The aim of the current work is to compare the effects of bulk zinc oxide and zinc oxide nanoparticles (ZnO-NPs) on the growth performance, feeding behavior, and zinc residues in tissues with the associated histopathological alterations in chicken. Meanwhile, the antibacterial activity against the isolated E. coli O78 strain was evaluated. Ninety Hubbard one-day-aged broiler chicks were divided into 3 groups, 30 each: birds of the 1st group fed a basal ration, those of the 2nd group fed a ration containing zinc oxide at a dose of 3000 mg/kg diet, and chicks of the 3rd group are given a ration containing ZnO-NPs at a dose of 90 mg/kg diet from 2 to 20 days age. The experiment lasted for 35 days. Feed choice test was done at the 3rd week of age on another 12 birds. Results revealed that birds fed with ZnO-NPs showed an improvement in body weight compared with the zinc oxide-administered group. There was no reluctance from birds to both diets supplemented with either zinc oxide or ZnO-NPs, with a constant preference to ZnO-NPs diet throughout the 5-min test. The highest levels of zinc were detected in the livers, kidneys, lungs, and muscles in the 1st day following cessation of drug administration. There was no significant effect on the levels of creatinine, uric acid, AST, and ALT. Mild to moderate degenerative changes as well as necrosis could be detected in the livers and hearts following both treatments. In conclusion, nano-zinc oxide could be practically used in broiler feed at a dose of 90 mg/kg diet instead of bulk zinc oxide, at a dose of 3000 mg/kg diet, with an improved body weight. Both supplements caused no significant effects on serum parameters and had the same antibacterial activity against E. coli O78.

Impacts of zinc oxide nano and bulk particles on redox-enzymes of the Punica granatum callus.

The structure and function of cellular membranes were sustained by redox-enzymes. We studied the interaction between the oxidative stress caused by excessive accumulation of ZnO-nanoparticles (ZnO-NPs) in plants and the role of redox-enzymes that can alleviate this stress. The crude callus extract from pomegranate, which was treated with 0, 10, and 150 µg mL-1 ZnO-NPs or bulk particles (ZnO-BPs), was applied to study the activity and kinetics of redox-enzymes. The elevated ZnO-NPs, enhanced the lipoxygenase and polyphenol oxidase activity, while the ZnO-BPs did not modify them. The activities of superoxide dismutase, catalase, and phenylalanine ammonia-lyase were induced under ZnO-NPs or BPs treatments, whilst the opposite trend of peroxidase was observed. Ascorbate peroxidase activity increased under ZnO-NPs treatments but decreased under ZnO-BPs. The kinetics activity of enzymes showed changes under different levels of NPs and BPs. Additionally, NPs or BPs treatments reduced the uptake of copper, iron, magnesium, but increased zinc accumulation in callus tissues. Meanwhile, these treatments enhanced the accumulation of manganese ions but did not affect the accumulation of potassium and phosphorous in ZnO-NPs or BPs-stressed calli. Collectively, these results gave a quantitative evaluation of the competition of zinc and other minerals on the carriers, and in addition, they provided a basis for how to control ZnO-NPs or BPs toxicity via redox-enzymes.

Exploitation of new approach to control of environmental pathogenic bacteria causing bovine clinical mastitis using novel anti-biofilm nanocomposite.

New approaches are required for prevention and control of biofilm-producing bacteria and consequently mitigating the health problems of bovine clinical mastitis. This work designed to determine prevalence rates of biofilm-producing bacteria that causing bovine clinical mastitis and evaluate the anti-biofilm effectiveness of novel nanocomposite of zinc-aluminum layered double hydroxide intercalated with gallic acid (GA) as chelating agent (Zn-Al LDH/GA) on the prevention and control of environmental pathogenic bacteria; Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus), and Coagulase-negative staphylococci (CNS), besides Listeria monocytogenes (L. monocytogenes) and assess the ability to use as an antimicrobial agent, and/or sanitizer for milking equipment. All samples (n = 230) involved clinical mastitis cow's milk (n = 50) beside environmental samples (n = 180) were collected then examined for isolation and identification of bacterial pathogens. Zn-Al LDH/GA nanocomposite was synthesized using co-precipitation method, then characterized by Fourier-transform infrared spectroscopy (FT-IR); X-ray diffraction (XRD); field emission scanning electron microscopy (FESEM); high-resolution transmission electron microscopy (HRTEM); thermogravimetric analysis (TGA); differential thermal analysis (DTA); zeta potential; DLS analysis; and Brunauer, Emmett, and Teller (BET) surface area. The anti-biofilm activity of nanocomposite against mastitis-causing bacteria was detected using the broth micro-dilution and disc-diffusion assay. Results, the minimum concentration of Zn-Al LDH/GA that inhibited the growth of gram-positive and negative bacteria, were 312-625 and 5000 µg/mL, respectively. The LD50 of Zn-Al LDH/GA was determined in mice at 1983.3 mg/kg b.wt. As a conclusion, Zn-Al LDH/GA nanocomposite proved its efficiency as an antimicrobial agent and/or sanitizer used for cleaning of milking equipment, due to it could inhibit the growth and multiplication of potentially pathogenic bacteria that causing clinical mastitis and its formation of biofilm on the milking equipment. Zn-Al LDH/GA was found to use under varying pH conditions compared with other commercial sanitizer used besides the formation of nanocomposite increases the material stability.

Cynara scolymus leaves extract alleviates nandrolone decanoate-induced alterations in testicular function and sperm quality in albino rats.

Nandrolone decanoate (ND) is a commonly used anabolic-androgenic steroid. These drugs are illegally self-administered by athletes to enhance their sports performance. However, their abuse could influence the testicular function and fertility. The main objective of this study was to evaluate the possible protective effects of Cynara scolymus leaf extract (CLE) on ND-induced testicular dysfunction in rats. Five groups of adult male rats (10 rats each) were used. Group I rats received only saline and served as controls. Group II rats were injected with a vehicle once weekly, while group III rats received intramuscular injections of ND (20 mg/kg/week for 60 days). Group IV rats orally received 1 g/kg/day of CLE and group V rats received ND and CLE at the aforementioned doses. The results revealed that ND has a negative impact on the testicular function as evidenced by the significant increases (p ≤ 0.05) in testicular malondialdehyde concentration and serum non-prostatic acid phosphatase activity, as well as the significant decreases in serum testosterone levels, testicular weight, glutathione concentration, catalase enzyme activity, and total antioxidant capacity. These results were accompanied by considerable alterations of sperm characters and histopathological studies of the testicular tissue. However, co-treatment with CLE extract significantly alleviated (p ≤ 0.05) almost all ND-induced pathological alterations. In conclusion, co-treatment of ND-intoxicated rats with CLE ameliorated the toxic effects of ND on the testicular structure and function, probably due to its antioxidant activity.

The effects of abamectin on oxidative stress and gene expression in rat liver and brain tissues: Modulation by sesame oil and ascorbic acid.

The present work was designed to assess the modulatory effects of sesame oil (SO) and ascorbic acid (AA) on abamectin (ABM)-induced oxidative stress and altered gene expression of hepatic cytochrome P450 2E1 (CYP-2E1), p38 MAPK, and caspase-3 and cerebral P-glycoprotein (Abcb1a receptor). Male rats were distributed into five groups (6 rats/group), receiving distilled water, ABM 2 mg/kg bwt 1/5 LD50 orally for 5 days, ABM + AA 100 mg/kg bwt orally, ABM + SO 5 ml/kg bwt orally, or ABM + SO + AA at the aforementioned doses. Nineteen compounds were identified in the SO sample by GC-MS analysis, including tetradecane,2,6,10-trimethyl, octadecane, 1-hexadecanol,2-methyl, and octadecane,6-methyl. Abamectin significantly upregulated the hepatic CYP-2E1 expression with excess generation of oxidative radicals, as evident by the significant depletion of reduced glutathione and elevation of malondialdehyde concentration (p ≤ 0.05) in rat liver and brain tissues. Further, ABM significantly increased TNF-α concentration, the expression of caspase-3 and p38 MAPK in the liver, as well as p-glycoprotein and GABA-A receptor in the brain. These results were in line with the observed histopathological changes. Sesame oil and/or AA supplementation alleviated ABM-induced cell damage by modulating all tested parameters. In conclusion, ABM induces oxidative stress and increases the expression of CYP-2E1, caspase-3, and p38 MAPK in the liver, as well as P-gp and GABA-A receptor in the brain. These effects could be ameliorated by SO and AA, alone and in combination, probably due to their anti-oxidant, anti-apoptotic, and gene-regulating activities.

The role of calcium, silicon and salicylic acid treatment in protection of canola plants against boron toxicity stress.

Boron (B) toxicity often limits crop yield and the quality of production in agricultural areas. Here, we investigated the effects of calcium (Ca), silicon (Si) and salicylic acid (SA) on development of B toxicity, B allocation in canola (Brassica napus cultivar Sarw 4) and its role in non-enzymatic antioxidants in relation to yield of this cultivar under B toxicity. Canola seedlings were subjected to four B levels induced by boric acid in the absence or presence of Ca, Si and SA. The results showed that Ca, Si and SA addition ameliorated the inhibition in canola growth, water content (WC), and improved siliqua number, siliqua weight and seed index. The B content in shoots and roots and total B accumulation in the whole plant were increased in control plants under B-toxicity-stress, and these parameters were significantly decreased by addition of Ca, Si and SA. The shoot ascorbate pool (ascorbate, AsA, and dehydroascorbate, DHA), α-tocopherol and phenolics (free and bound) were increased under B toxicity, and were significantly decreased in most cases by addition of Ca, Si and SA, except α-tocopherol, which increased at low B levels (0, 25 and 50 mg kg soil-1). The glutathione content did not obviously change by B stress, while added Ca, Si and SA inhibited its accumulation under B stress. In addition, B toxicity reduced the shoot flavonoids content; however, this reduction was not alleviated by the use of Ca, Si and SA treatments. It could be concluded that growth and yield of canola plants grown under high B concentration improved after external application of Ca, Si or SA.

Effect of salinity and sodicity stresses on physiological response and productivity in Helianthus annuus.

Soil salinity and sodicity (alkalinity) are serious land degradation issues worldwide that are predicted to increase in the future. The objective of the present study is to distinguish the effects of NaCl and Na(2)CO(3) salinity in two concentrations on the growth, lipoxygenase (LOX) activity, membrane integrity, total lipids, yield parameters and fatty acids (FAs) composition of seeds of sunflower cultivar Sakha 53. Plant growth, LOX activity and malondialdehyde (MDA) content were reduced by salts stresses. On the contrary, salinity and alkalinity stress induced stimulatory effects on membrane permeability, leakage of UV-metabolites from leaves and total lipids of sunflower shoots and roots. Crop yield (plant height, head diameter, seed index and number of seeds for each head) that is known as a hallmark of plant stress was decreased by increasing concentrations of NaCl and Na(2)CO(3) in the growth media. Fatty acid methyl esters (FAME) composition of salt-stressed sunflower seeds varied with different levels of NaCl and Na(2)CO(3).

Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies.

Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries.

Ectopic expression of pumpkin gibberellin oxidases alters gibberellin biosynthesis and development of transgenic Arabidopsis plants.

Immature pumpkin (Cucurbita maxima) seeds contain gibberellin (GA) oxidases with unique catalytic properties resulting in GAs of unknown function for plant growth and development. Overexpression of pumpkin GA 7-oxidase (CmGA7ox) in Arabidopsis (Arabidopsis thaliana) resulted in seedlings with elongated roots, taller plants that flower earlier with only a little increase in bioactive GA4 levels compared to control plants. In the same way, overexpression of the pumpkin GA 3-oxidase1 (CmGA3ox1) resulted in a GA overdose phenotype with increased levels of endogenous GA4. This indicates that, in Arabidopsis, 7-oxidation and 3-oxidation are rate-limiting steps in GA plant hormone biosynthesis that control plant development. With an opposite effect, overexpression of pumpkin seed-specific GA 20-oxidase1 (CmGA20ox1) in Arabidopsis resulted in dwarfed plants that flower late with reduced levels of GA4 and increased levels of physiological inactive GA17 and GA25 and unexpected GA34 levels. Severe dwarfed plants were obtained by overexpression of the pumpkin GA 2-oxidase1 (CmGA2ox1) in Arabidopsis. This dramatic change in phenotype was accompanied by a considerable decrease in the levels of bioactive GA4 and an increase in the corresponding inactivation product GA34 in comparison to control plants. In this study, we demonstrate the potential of four pumpkin GA oxidase-encoding genes to modulate the GA plant hormone pool and alter plant stature and development.