To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX ...hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.
Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against ...S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their antimicrobial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.
Highlights
A series of new N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised targeting the multidrug efflux pump (MATE) guided by the pharmacophoric features of the co-crystallized native inhibitor of the target protein.
The newly synthesised compounds were assessed through in vitro, in vivo, and in silico approaches.
Using the agar well diffusion assay, the antibacterial activities of the synthesised compounds were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas, their antifungal activities were screened against C. albicans.
The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the synthesised compounds were investigated on variable microbial species.
Compounds (4h and 4i) -as the broader and superior members regarding their antimicrobial effects- were further evaluated via in vivo testing using bio-chemical analysis and liver/kidney histological examination.
A molecular docking study and ADMET in silico studies were performed.
A structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.
This study was carried out using 22 promising restorer lines of rice and their parental lines to study genetic variability and genetic advance for yield and yield-associated grain quality traits and ...floral traits. These genotypes are evaluated in a replicated trial using Randomized Complete Block Design (RCBD) with three replications at the Experimental Farm of Sakha Agricultural Research Station, Sakha, Kafr El-Sheikh, Egypt, during the seasons from 2012 to 2020. Analysis of variance revealed that highly significant variations were observed among the genotypes for all the studied characters. Both GCV% and PCV% were high for the number of spikelets per panicle, the number of filled grains per panicle, and panicle weight. The genetic advance in the percentage of mean was high for days to plant height, panicle length, number of spikelets per panicle, number of filled grains per panicle, panicle weight, grain yield per plant, anther length, anther breadth, duration of floret opening, and head rice percentage. Mean performance of the rice genotypes indicated that the genotypes NRL 59, NRL 55, NRL 62, NRL 63, NRL 66, and NRL 54-2 were promising for grain yield and associated desirable traits. Thus, some of these promising lines can be promoted as a new rice variety and could be used as a source for developing new hybrid combinations in hybrid rice breeding programs. The percentage of advantage over better parent and Giza 178 as the commercial variety was significant and there were highly significant desirable values among the genotypes for all the studied traits in the two years, indicating that the selection is effective in the genetic improvements for these traits.
In this study, we evaluated bioinspired titanium dioxide nanoparticles (TiO2 NPs) that elicited biochemical and proteome modifications in wheat plants under the biotic stress caused by Puccinia ...striiformis f. sp. tritici (Pst). Biosynthesis of TiO2 NPs was confirmed using UV–Vis spectrophotometry, energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. We found that the nanoparticles with crystalline nature were smaller than 100 nm. The results of FTIR analysis showed the presence of potential functional groups exhibiting O-H, N-H, C-C, and Ti-O stretching. The TiO2 NPs of different concentrations (20, 40, 60, and 80 mg L−1) were exogenously applied to wheat plants under the biotic stress caused by Pst, which is responsible for yellow stripe rust disease. The results of the assessment of disease incidence and percent disease index displayed time- and dose-dependent responses. The 40 mg L−1 TiO2 NPs were the most effective in decreasing disease severity. The bioinspired TiO2 NPs were also evaluated for enzymatic (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), and nonenzymatic metabolites (total proline, phenolic, and flavonoid contents) in wheat plants under stripe rust stress. The 40 mg L−1 TiO2 NPs were effective in eliciting biochemical modifications to reduce biotic stress. We further evaluated the effects of TiO2 NPs through gel- and label-free liquid chromatography-mass spectrometry (LC-MS) proteome analysis. We performed proteome analysis of infected wheat leaves and leaves treated with 40 mg L−1 TiO2 NPs under stripe rust stress. The functional classification of the proteins showed downregulation of proteins related to protein and carbohydrate metabolism, as well as of photosynthesis in plants under biotic stress. An upregulation of stress-related proteins was observed, including the defense mechanisms and primary metabolic pathways in plants treated with 40 mg L−1 TiO2 NPs under stress. The experimental results showed the potential of applying biogenic TiO2 NPs to combat fungal diseases of wheat plants and provided insight into the protein expression of plants in response to biotic stress.
Nanotechnology has come a long way in our lives. However, it maintains some negative effects on the environment. This study aims to use the land snail
Helix aspersa
as a bioindicator. Titanium ...dioxide nanoparticles (TiO
2
NPs) had been used at 70 and 140 µg/L for two weeks by the spraying method. The oxidative biomarkers, condition index (CI), DNA damage, hemocyte count, and phagocytic activity were estimated. The toxicity of TiO
2
NPs was determined (LC
50
= 544 µg/L). The exposure to TiO
2
NPs caused a significant reduction of the activities of superoxide dismutase (SOD) and catalase (CAT) in the digestive gland of
Helix aspersa
(the activity of CAT was 3.4 ± 0.1 (
P
= 0.001), SOD was 11 ± 1 (
P
= 0.0002) at concentration 140 µg/L after two weeks). The activity of glutathione peroxidase (GPX) was (1.13 ± 0.01 µ/mg protein at 140 µg/L compared with controls (5.47 ± 0.01 µ/mg protein). The treatment caused DNA damage in the hemocytes (tail DNA % = 8.66 ± 0.02 and tail moment = 52.99 ± 0 at140 µg/L (
P
= 0.002)). In the digestive gland, both tail DNA % and tail moment increased (tail moment = 78.38 ± 0.08 compared with control = 2.29 ± 0.09 (
P
= 0.0001)). The total count of hemocytes significantly decreased after two weeks (the average number was 71 ± 1.5 compared with controls 79 ± 1.1 at 140 µg/L). Furthermore, TiO
2
NPs caused histological alterations in the digestive gland of
Helix aspersa
. It can be concluded that the
Helix aspersa
can be used as environmental pollution bioindicator. A comprehensive evaluation of toxic effects induced by TiO
2
NPs in vivo assays must be investigated.
Salinity is widespread environmental stress that poses great obstacles to rapeseed development and growth. Polyamines are key plant growth regulators that play a pivotal role in regulating salt ...tolerance. Rapeseed (Brassica napus L.) seedlings were treated by spermine (Spm) and spermidine (Spd) versus untreated control under salt stress conditions. It was detected that the Spd-treated plants had significantly elevated chlorophyll and proline content and maintained higher photosystem II (PSII) activity than those treated with Spm as well as untreated control under salt-stressed conditions. Similarly, Spd alleviated the devastating effects of NaCl stress on CO2 assimilation and significantly elevated Rubisco activity (ribulose 1,5-bisphosphate carboxylase/oxygenase). The application of Spd also enhanced the activities of different antioxidant enzymes under NaCl stress. It modulated their respective transcription levels, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and dehydroascorbate reductase (DHAR). In addition, exogenously sprayed Spd enhanced the polyamine pathway as observed by upregulated transcription of polyamine oxidase (PAO) and diamine oxidase (DAO). The Spd application enhanced expressions of Calvin cycle enzyme related genes such as Rubisco small subunit, Rubisco large subunit, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglyceric acid kinase (PGK), triose-3-phosphate isomerase (TPI), fructose-1,6-bisphosphate aldolase (FBA), sedoheptulose-1,7-bisphosphatase (SBPase), and fructose-1,6-bisphosphate phosphatase (FBPase). Consequently, this study demonstrates that exogenous application of Spd has a valuable role in regulating antioxidant enzyme activity, polyamine pathway, and Calvin cycle enzyme-related genes to alleviate salt stress damage in the plants.
Papain and pepsin-hydrolyzed whey protein (PAH and PEH, respectively) were prepared and characterized for its degree of hydrolysis, chemical constituents (amino acid and peptides) and antioxidant ...activity. A field experiment was conducted at El Salheya El Gedida City, Sharqia, Egypt, during the seasons 2019 and 2020, to investigate the biological action of the foliar spray of PAH and PEH on the growth and yield of pea plants cultivated in a clay loam soil. Foliar application of the papain and pepsin-hydrolyzed whey protein (PAH and PEH, respectively) at 1000 and 2000 mg/L was applied three times after 25, 35 and 45 days from planting. All protein foliar spray treatments had significant positive effects on the uptake of N, P and K, simultaneously increasing the contents of all the photosynthetic pigments (Chlorophyll a, Chlorophyll b and Carotenoids) in a concentration-dependent manner. The most conspicuous increase was seen in Chlorophyll b (105% increase), followed by Carotenoids (91% increase). Generally, the favorable increases caused by the second level of application (2000 mg/L) were nearly 2-3 times that of the low level (1000 mg/L). Pod growth and formation indicators, e.g., no. of pod/plant, pod length and no. of seeds/pod, responded more evidently to the hydrolyzed than the intact form of whey protein treatments. Hydrolyzed whey protein foliar spray treatments achieved significantly higher increases in the global field yield components of
plants than the intact form, where peptic hydrolysates were significantly superior to papain hydrolysate. The treatment PEH (2000 mg/L) can be recommended as the most effective bio-stimulating foliar spray treatment for higher plant productivity when applied 25, 35 and 45 days after planting.
Background
Plant growth regulators are widely used in agriculture for increasing the growth and ripening of plants, but they endanger the aquatic ecosystem. The current study assessed the effect of ...sublethal exposure to RIPEX 48% EC concentrations (8 and 16 µL/L) on oxidative stress parameters, sex hormones, immune potential enzymes, differential hemocyte counts, and the histopathology of digestive glands and ovotestis in
Biomphalaria alexandrina
snails.
Results
RIPEX exposure caused an overall increase in Superoxide dismutase and Glutathione-S-Transferase activities in
B. alexandrina
. However, extreme RIPEX exposure inhibits SOD activity in snails. Malondialdehyde activity showed an increase in
B. alexandrina
exposed to both concentrations after all exposure periods. RIPEX also caused a significant increase in testosterone in snails exposed to 16 µL/L, it did, however, reduce hormone levels in snails exposed to 8 µL/L at 7 days. Regarding estradiol, there was a significant increase after 3 days of exposure to 16 µl/L and 7 days of exposure to 8 µL/L. RIPEX exposure also increased the activities of Myeloperoxidase and Adenosine deaminase enzymes in the digestive glands of snails. It increased the total hemocyte count of exposed snails as well as the number of granulocytes. Snail digestive glands and ovotestis showed pathological alterations after 7 days of RIPEX exposure.
Conclusions
These findings suggest that RIPEX is toxic to
B. alexandrina
and that this snail can be used as a bioindicator for environmental contamination with plant growth regulators.
Abstract
Musa acuminata
(MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic ...approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS
2
fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-
O-β
-
d
-glucoside, luteolin-7-
O-β
-
d
-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250–500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilβ6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.
Bisphenol A (BPA) is one of the most potent endocrine-disrupting chemicals (EDCs) that adversely affect aquatic organisms. The present investigation explored the effects of exposure to BPA at 0.1 and ...1 mgL
−1
concentrations on the fecundity of
Biomphalaria alexandrina
, snail's infection with
Schistosoma mansoni
, and histology of the ovotestis and topographical structure of
S. mansoni
cercariae emerged from exposed snails. The 24 h LC
50
and LC
90
values of BPA against
B. alexandrina
were 8.31 and 10.88 mgL
−1
BPA, respectively. The exposure of snails to 0.1 or 1 mgL
−1
BPA did not affect the snail's survival. However, these concentrations caused an increase in the reproductive rate (R
o
) of infected snails. A slight decrease in egg production was observed in snails exposed to 0.1 mgL
−1
BPA after being infected (infected then exposed). However, a significant increase in egg production was noted in snails exposed to 1 mgL
−1
BPA after infection with
S. mansoni
. Histopathological investigations indicated a clear alteration in the ovotestis tissue structure of exposed and infected-exposed groups compared to the control snails. Chronic exposure to BPA caused pathological alterations in the gametogenic cells. SEM preparations of
S. mansoni
cercariae emerged from infected-exposed snails showed obvious body malformations. From a public health perspective, BPA pollution may negatively impact schistosomiasis transmission, as indicated by the disturbance in cercarial production and morphology. However, it has adverse effects on the reproduction and architecture of reproductive organs of exposed snails, indicating that
B. alexandrina
snails are sensitive to sublethal BPA exposure.
Graphical abstract