A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies.

Structural and biological studies were conducted on the novel complexes [Fe(U)2(H2O)2]Cl3 (FeU) and [Ru(U)2(H2O)2]Cl3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies.

The anti-toxic effect of the date palm fruit extract loaded on chitosan nanoparticles against CCl4-induced liver fibrosis in a mouse model.

The liver is the most important organ in the body. Hepatocyte oxidative damage occurs to excess ROS. Liver fibrosis is a mechanism that the immune system uses to treat extreme inflammation by repairing damaged tissue with the creation of a scar. The outcome of fibrosis may be reversed by consuming natural plant extracts with high ROS-scavenging ability. The date palm fruits contain caffeic acid, gallic acid, syringic acid, and ferulic acid, which have anti-inflammatory, antioxidant, and hepatoprotective properties. This study aimed to prepare a date fruit extract, load it onto chitosan nanoparticles, and compare its anti-fibrotic activity with the unloaded crude extract in the CCl4-mouse model. Our findings show that nanocomposite (Cs@FA/DEx) has anti-fibrotic properties and can improve liver function enzymes and endogenous antioxidant enzymes by inhibiting cell apoptosis caused by CCl4-induction in mice. Furthermore, significantly reduced CD95 and ICAM1 levels and down-regulation of TGFß-1 and collagen-α-1 expression demonstrated the anti-fibrotic effects of the Cs@FA/DEx. Therefore, the Cs@FA/DEx might be an innovative supplement for inhibiting liver fibrosis and hepatocyte inflammation induced by chemical toxins. Besides, this nano-supplement could be a promising anti-hepatocellular carcinoma agent as it has potent in vitro anticancer activity against the HePG2 cell line.

Avocado peel extract loaded on chitosan nanoparticles alleviates urethane toxicity that causes lung cancer in a mouse model.

Lung cancer progresses without obvious symptoms and is detected in most patients at late stages, causing a high rate of mortality. Avocado peels (AVP) were thought to be biowaste, but they have antioxidant and anticancer properties in vitro. Chitosan nanoparticles (Cs-NPs) were loaded with various plant extracts, increasing their in vitro and in vivo anticancer activities. Our goal was to load AVP onto Cs-NPs and determine the role of AVP-extract or AVP-loaded Cs-NPs in controlling the progression of lung cancer caused by urethane toxicity. The AVP-loaded chitosan nano-combination (Cs@AVP NC) was synthesized and characterized. Our in vitro results show that Cs@AVP NC has higher anticancer activity than AVP against three human cancer cell lines. The in vivo study proved the activation of apoptosis in lung cancer cells with the Cs@AVP NC oral treatment more than the AVP treatment. Additionally, Cs@AVP NC-treated animals showed significantly higher p53 and Bax-expression levels and lower NF-κB p65 levels in their lung tissues than in positive control animals. In conclusion, our study demonstrated the superior anticancer potency of Cs@AVP NC over AVP extract and its ability to inhibit lung cancer proliferation. Therefore, oral consumption of Cs@AVP NC might be a promising treatment for lung cancer.

Paullinia cupana seed extract ameliorated methotrexate-induced testicular dysfunction through the regulation of antioxidants, inflammatory, apoptosis/anti-apoptosis, and steroidogenesis-associated genes.

Methotrexate (MXT) is a medication used for cancer and rheumatoid treatment with severe organs toxicity as a side effect. Paullinia cupana (Guarana) is a plant with pleiotropic functions used to overcome the side effects of some chemotherapeutic medications. Current study aimed to examine the possible protective effect of guarana against oxidative stress induced by a single dose of MTX in testis. Forty male mice were divided into 4 groups (8 weeks old; 30 g weight), 1st group is negative control. The 2nd group is positive intoxicated group, received a single dose of MTX intraperitoneally (IP; 20 mg/kg BW in saline) on day 7. The 3rd group received guarana seed extract orally (300 mg/kg BW daily) for 12 days. The protective group was given guarana seed extract orally for 1 week, then on day 7 injected with MTX, and continued with guarana for extra 5 days. Blood was taken for biochemical measurement (hormones, antioxidants, cytokines, and oxidative stress biomarkers). Testicular tissues were taken for gene quantification (qRT-PCR), testicular oxidative stress activity (malondialdehyde; MDA, and SOD) and comet assay (sperm DNA damage), and histopathological changes at the end of experimental design. MTX intoxication caused a decrease in testicular SOD, GSH, and catalase and an increase in serum and tissue levels of MDA. Biomarkers of oxidative stress were increased by MTX intoxication, and were ameliorated by guarana administration to MTX-intoxicated mice. Guarana prevented the increase in IL-1ß and IL-6 levels compared to mice intoxicated with MTX alone. MTX upregulated the expression of caspase-3 and downregulated Bcl-2 expression using qRT-PCR analysis. These negative impacts of MTX were protected by guarana pre-administration. MTX decreased reproductive hormones and altered spermogram parameters (sperm concentration and motility, and percentage of live and dead sperms). In addition, the mRNA expression of steroidogenesis-associated genes, such cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 17ß hydroxyl steroid dehydrogenase (17ß-HSD) was downregulated in the MTX-treated group, all were prevented by guarana administration. The sperm DNA damage revealed by a comet assay was increased in MTX group and was reversed to control levels by guarana supplementation. Finally, testis histology of MTX-group showed marked spermatocytes vacuolization and a decrease in spermatogenesis. Guarana administration abrogated histopathological changes reported in the Leydig cells and testicular tissues. In conclusion, guarana has the potential as a supplement medication to antagonize testicular oxidative stress induced by methotrexate.

Resveratrol treatment modulates several antioxidant and anti-inflammatory genes expression and ameliorated oxidative stress mediated fibrosis in the kidneys of high-fat diet-fed rats.

Objective: Resveratrol is a polyphenolic compound that possesses strong antioxidant and anti-inflammatory activities. This study evaluated the effects of resveratrol on oxidative stress, fibrosis and multiple genes regulation in the kidneys of high fat (HF) diet-fed rats. Methods: Wistar rats were fed with HF diet for eight weeks. These rats were also treated with resveratrol for eight weeks. Finally, kidney tissue samples were isolated from all sacrificed rats. The histological changes, creatinine and uric acid levels, oxidative stress parameters such as malondialdehyde (MDA), nitric oxide, and advanced oxidation protein product (AOPP) levels were analyzed. The antioxidant enzymes such as catalase, superoxide dismutase (SOD) activities and reduced glutathione (GSH) levels; gene expression of inflammatory and fibrosis-related genes namely, inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta1 (TGF-ß1), and collagen-1 were assessed. Moreover, gene expression of oxidative stress-related genes such as nuclear factor erythroid 2-related factor 2 (Nrf-2), SOD, catalase, and glutathione reductase, were also assessed. Results: HF diet-fed rats showed increased creatinine and uric acid levels in plasma which were lowered by resveratrol treatment. The study findings also revealed that resveratrol counterbalanced the oxidative stress and prevented the expression of the inflammatory genes; restored the catalase and SOD activities followed by the up-regulation of antioxidant genes expression in the kidneys of HF diet-fed rats. HF diet caused the Nrf-2 down-regulation followed by the decreased expression of HO-1 and HO-2 genes, which was restored by resveratrol treatment. Moreover, the histological assessment showed lipotoxicity and increased fibrosis in the kidneys of HF diet-fed rats. Resveratrol prevented the kidney fibrosis probably by limiting oxidative stress, inflammation, and down-regulating TGF-ß1 mediated signaling pathway. Conclusion: In conclusion, resveratrol treatment showed beneficial effects in preventing oxidative stress and fibrosis in the kidneys of HF diet-fed rats probably by modulating the gene expression of oxidative stress and inflammation related factors and enzymes.

An In Vitro and In Silico Perspective Study of Seed Priming with Zinc on the Phytotoxicity and Accumulation Pattern of Arsenic in Rice Seedlings.

Arsenic (As) contamination of the rice agro-ecosystem is a major concern for rice farmers of South East Asia as it imposes a serious threat to human and animal life; thus, there is an unrelenting need to explore the ways by which arsenic stress mitigation could be achieved. In the present investigation, we explore the effect of zinc (Zn2+) supplementation using the seed priming technique for the mitigation of As-induced stress responses in developing rice seedlings. In addition to the physiological and biochemical attributes, we also studied the interactive effect of Zn2+ in regulating As-induced changes by targeting antioxidant enzymes using a computational approach. Our findings suggest that Zn2+ and As can effectively modulate redox homeostasis by limiting ROS production and thereby confer protection against oxidative stress. The results also show that As had a significant impact on seedling growth, which was restored by Zn2+ and also minimized the As uptake. A remarkable outcome of the present investigation is that the varietal difference was significant in determining the efficacy of the Zn2+ priming. Further, based on the findings of computational studies, we observed differences in the surface overlap of the antioxidant target enzymes of rice, indicating that the Zn2+ might have foiled the interaction of As with the enzymes. This is undoubtedly a fascinating approach that interprets the mode of action of the antioxidative enzymes under the metal/metalloid-tempted stress condition in rice by pointing at designated targets. The results of the current investigation are rationally significant and may be the pioneering beginning of an exciting and useful method of integrating physiological and biochemical analysis together with a computational modelling approach for evaluating the stress modulating effects of Zn2+ seed priming on As-induced responses in developing rice seedlings.

Puerarin ameliorates nonalcoholic fatty liver in rats by regulating hepatic lipid accumulation, oxidative stress, and inflammation.

Nonalcoholic fatty liver disease (NAFLD) has become one of the public health problems globally. The occurrence of NAFLD is usually accompanied by a series of chronic metabolic diseases, with a prevalence rate is 25.24% among adults worldwide. Therefore, NAFLD seriously affects the quality of life in patients and causes a large economic burden. It has been reported that puerarin has the function of lowering the serum lipids, but due to the complexity of NAFLD, the specific mechanism of action has not been clarified. The aim of this study was to evaluate the preventive or ameliorating effects of two doses of puerarin (0.11% and 0.22% in diet) on high-fat and high-fructose diet (HFFD)-induced NAFLD in rats. The rats were fed with HFFD-mixed puerarin for 20 weeks. The results showed that puerarin ameliorated the levels of lipids in the serum and liver. Further exploration of the mechanism found that puerarin ameliorated hepatic lipid accumulation in NAFLD rats by reducing the expression of Srebf1, Chrebp, Acaca, Scd1, Fasn, Acacb, Cd36, Fatp5, Degs1, Plin2, and Apob100 and upregulating the expression of Mttp, Cpt1a, and Pnpla2. At the same time, after administration of puerarin, the levels of antioxidant markers (superoxide dismutase, glutathione peroxidase, and catalase) were significantly increased in the serum and liver, and the contents of serum and hepatic inflammatory factors (interleukin-18, interleukins-1ß, and tumor necrosis factor α) were clearly decreased. In addition, puerarin could ameliorate the liver function. Overall, puerarin ameliorated HFFD-induced NAFLD by modulating liver lipid accumulation, liver function, oxidative stress, and inflammation.

Design, Synthesis and Cytotoxic Activity Evaluation of Newly Synthesized Amides-Based TMP Moiety as Potential Anticancer Agents over HepG2 Cells.

A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC50 values 0.65 and 0.92 µM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of caspase 3/7. Caspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of caspase 3/7 may occur via mitochondrial apoptotic pathway.

Characterization of the Impacts of Living at High Altitude in Taif: Oxidative Stress Biomarker Alterations and Immunohistochemical Changes.

At high elevations, the human body experiences a number of pathological, physiological, and biochemical changes, all of which have adverse impacts on human health and organ vitality. This study aimed to investigate the alterations in the liver and kidney biomarkers, oxidative stress markers, gene expression, and cellular histology of rats maintained at high altitudes and normal sea level. A total of twenty male Wistar rats at 2 months of age were randomly assigned to two groups. The rats in group A were maintained at normal sea level in Jeddah, whereas rats in group B were maintained in an area in Taif 2600 m above sea level. After 2 months of housing, orbital blood samples were collected for the analysis of significant biochemical indicators of oxidative stress biomarkers of the liver and kidneys. Liver and kidney tissues from both groups were taken to examine the hepatorenal changes occurring at the biochemical, histological, immunohistochemical, and genetic levels. The results revealed substantial increases in the serum levels of liver and kidney biomarkers (GPT, GOT, urea, and creatinine) and decreases in the serum levels of antioxidant biomarkers (SOD, catalase, GSH, and NO). In parallel, the levels of the malondialdehyde (MDA) tissue damage marker and inflammatory cytokines (IL-1ß, TNF-α, and IFN-γ) were increased in the high-altitude group compared to the normal sea level group. In addition, there were significant alterations in the oxidative and inflammatory status of rats that lived at high altitude, with considerable upregulation in the expression of hepatic VEGF, type 1 collagen, Cox-2, TNF-α, and iNOS as well as renal EPASI, CMYC, HIF-α, and EGLN-2 genes in the high-altitude group compared with controls housed at normal sea level. In conclusion, living at high altitude induces hepatorenal damage and biochemical and molecular alterations, all of which may serve as critical factors that must be taken into account for organisms living at high altitudes.

A comparative study among dietary supplementations of antibiotic, grape seed and chamomile oils on growth performance and carcass properties of growing rabbits.

The main objective of this study was to evaluate the effect of chamomile oil (Ch), grape seed oil (GS), their mixture and antibiotic (colistin) (AN) as feed addetives on the productivity of growing rabbits as well as in vitro study to evaluate the antimicrobial activity of both Ch and GS oils. To achive this objective, a total of 96 New Zealand (NZW) weaned rabbits, 5 weeks-old were randomly allotted into eight groups. Rabbits were kept under observation for eight weeks and the trial ended at thirteen weeks-old. The experimental treatments were: 1) Basal diet (BD); 2) BD + antibiotic; 3) BD + 0.5 ml GS/ kg diet; 4) BD + 1.0 ml GS/ kg diet; 5) BD + 1.5 ml GS/ kg diet; 6) BD + 0.5 ml Ch/ kg diet; 7) BD + 1.0 ml Ch/ kg diet and 8) BD + 1.5 Ch/ kg diet. Live body weight (LBW) was markedly elevated (p < 0.05) in groups fed on ration included feed additives compared with the control at weeks 9 and 13 of age. Cumulative body weight gain (BWG) and feed intake (FI) increased (p < 0.05) throughout 5-9 and 5-13 weeks of age in rabbits fed rations plus the studied additives. Feed conversion ratio (FCR) was insignificantly altered by dietary feed additives. Spleen and intestine relative weights reduced (p < 0.05) in groups treated with different studied additives. In view of the experiment finings, it could be concluded that dietary supplementation of GS and Ch have a positive impact on the productivity of growing rabbits than that of the control and antibiotic-treated groups.

Quercetin Abrogates Oxidative Neurotoxicity Induced by Silver Nanoparticles in Wistar Rats.

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1ß, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue.

Chrysin abrogates gibberellic acid-induced testicular oxidative stress and dysfunction via the regulation of antioxidants and steroidogenesis- and apoptosis-associated genes.

GA3 is widely used as a growth stimulant in agricultural regions. The long-term use of GA3 can cause organs damage. Chrysin is a flavonoid found in nature that is commonly used to treat organ toxicity. In this study, we examined the effect of chrysin on the testes function of GA3-affected rats. A total of 24 male Wistar rats were divided into 4 groups. Saline was given to the control group. The chrysin group was given orally 50 mg/kg/BW of chrysin in saline. The GA3 group received a daily oral gavage of GA3 (55 mg/kg/BW). The protective group (chrysin + GA3) was given chrysin and GA3 as those described in chrysin and GA3 groups. There were an increase in MDA levels in the serum and testicular tissue of GA3-treated group. Catalase, GSH, and SOD levels were all lowered in the GA3-treated rats. Chrysin dramatically reduced the harmful effects of GA3 by restoring reproductive hormone levels, altered sperm parameters, and antioxidant capabilities. Furthermore, GA3 reduced the quantitative expression of steroidogenesis genes StAR and 3-HSD, as well as Bcl2 genes, while it increased the apoptotic marker BAX; all were alleviated by the pre-administration of chrysin. The pre-administration of chrysin protected the GA3 group from spermatogenic vacuolation, interstitial edema, necrosis, and depletion. Chrysin inhibited oxidative stress and modulated antioxidant activity, as well as apoptosis-/anti-apoptosis-related mediators in the testes. Chrysin has the potential to repair GA3-induced testicular dysfunctions. This suggests that chrysin is preferable as a medication to mitigate GA3-induced oxidative damage in the testes. PRACTICAL APPLICATIONS: Chrysin has the potential to repair GA3-induced testicular dysfunctions. This suggests that chrysin is preferable as a medication to mitigate GA3-induced oxidative damage in the testes.

Phytogenic compounds from avocado (Persea americana L.) extracts; antioxidant activity, amylase inhibitory activity, therapeutic potential of type 2 diabetes.

Diabetes is a worldwide public health disease. Currently, the most effective way to treat diabetes is to mitigate postprandial hyperglycemia by inhibiting carbohydrate hydrolysis enzymes in the digestive system. Plant extracts are rich in bioactive compounds, which can be used in diabetes treatment. This study aims to evaluate the polyphenols content in ethanolic extracts of avocado fruit and leaves (Persea americana Mill.). Additionally, their antioxidant activity using DPPH, while the inhibition ability of α-amylase was examined by reacting different amounts of the extracts with α-amylase compared to acarbose as standard inhibitor. The active compounds were detected in the extracts by LC/MS. The obtained results showed that the leaf extract recorded a significant content of total phenolic compounds compared to the fruit extract (178.95 and 145.7 mg GAE /g dry weight, respectively). The total flavonoid values ​​ranged from 32.5 to 70.08 mg QE/g dry weight of fruit and leaves extracts, respectively. Twenty-six phytogenic compounds were detected in leaf and fruit extract by LC/MS. These compounds belong to fatty acids, sterols, triterpenes, phenolic acids, and flavonoids. The antioxidant activity of the extracts is due to the exist of phytogenic compounds, i.e., polyphenols and flavonoids. The antioxidant activity increased in a concentration dependant manner. Avocado fruit extract (1000 µg/mL) scavenged 95% of DPPH while leaf extract rummaged 91.03% of free radicals compared with Vit C and BHT. Additionally, higher α-amylase inhibitory activity was observed in fruit extract than the leaf extract, where the fruit and leaf extract (1000 µg/ml) inhibited the enzyme by 92.13% and 88.95%, respectively. The obtained results showed that the ethanolic extracts of avocado could have a significant impact on human health due to their high content of polyphenols.

Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1ß and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Borate Ameliorates Sodium Nitrite-Induced Oxidative Stress Through Regulation of Oxidant/Antioxidant Status: Involvement of the Nrf2/HO-1 and NF-κB Pathways.

The widespread industrial use of nitrite in preservatives, colorants, and manufacturing rubber products and dyes increases the possibilities of organ toxicity. Lithium borate (LB) is known as an antioxidant and an oxidative stress reliever. Therefore, this study is aimed at examining the effect of LB on nitrite-induced hepatorenal dysfunction. Twenty-eight male Swiss mice were divided into four equal groups. Group 1, the control group, received saline. Group 2 received LB orally for 5 consecutive days at a dose of 15 mg/kg bw. Group 3, the nitrite group, received sodium nitrite (NaNO2) on Day 5 (60 mg/kg bw intraperitoneally). Group 4, the protective group (LB + NaNO2 group), received LB for 5 days and then a single dose of NaNO2 intraperitoneally on Day 5, the same as in Groups 2 and 3, respectively. Samples of blood and kidney were taken for serum analysis of hepatorenal biomarkers, levels of antioxidants and cytokines, and the expression of genes associated with oxidative stress and inflammation. NaNO2 intoxication increased markers of liver and kidney functions yet decreased reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities in blood. NaNO2 also increased the expression of tumor necrosis factor (TNF-α), interleukin-1ß and interleukin-6 (IL-1ß and IL-6). Pre-administration of LB protected mice from oxidative stress, lipid peroxidation, and the decrease in antioxidant enzyme activity. Moreover, LB protected mice from cytokine changes, which remained within normal levels. LB ameliorated the changes induced by NaNO2 on the mRNA of nuclear factor erythroid 2-related factor 2 (Nfr2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), transforming growth factor-beta 2 (TGF-ß2), and glutathione-S-transferase (GST) as determined using quantitative real-time PCR (qRT-PCR). These results collectively demonstrate that LB ameliorated NaNO2-induced oxidative stress by controlling the oxidative stress biomarkers and the oxidant/antioxidant state through the involvement of the Nrf2/HO-1 and NF-κB signaling pathways.

Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats.

BACKGROUND: Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. RESULTS: Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. CONCLUSION: These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

The modulatory impacts of Glycyrrhiza glabra extract against methotrexate-induced testicular dysfunction and oxidative stress.

Glycyrrhiza glabra root (licorice) is a widely used herb for its beneficial effects on health. This study explored the protective effects of licorice extract against oxidative stress and testicular dysfunction caused by methotrexate (MTX). Mice were allocated into (i) negative control group that received saline; (ii) licorice extract group, orally administered with 200 mg/kg body weight (bw) licorice extract for 12 days; (iii) positive MTX-intoxicated group, injected with a single intraperitoneal dose of MTX (20 mg/kg bw) on day 7; and (iv) a protective group that received licorice extract for 12 days and then MTX on day 7 as in groups 2 and 3. Total proteins, albumin, globulins, malondialdehyde, glutathione peroxidase, reduced glutathione, IL-1, and IL-6 were measured in blood and testis samples collected from all groups. Testicular oxidative stress, serum reproductive hormones, and spermogram were examined. The expression of steroidogenesis-associated genes (translocator protein; and P450scc) was examined by quantitative real-time PCR. Bcl-2-associated X protein and cyclogenase-2 genes were examined by immunohistochemical analysis. The bioactive contents of licorice extract were confirmed by gas chromatography-mass spectrometry analysis. Pretreatment with licorice extract ameliorated the toxic effects of MTX on total proteins, albumin, and globulins and oxidative stress biomarkers and reversed the effect of MTX on examined serum and tissue antioxidants. Besides, MTX down-regulated mRNA expression of translocator protein and P450scc genes. Licorice extract averted the decrease in serum testosterone and the increase in IL-1ß and IL-6 levels induced by MTX. Moreover, MTX increased sperm abnormalities and percentage of dead sperms and reduced sperm motility. These changes were absent in the licorice preadministered group. Licorice prevented the increase in immunoreactivity of testis for Bcl-2-associated X protein and cyclogenase-2 that were overexpressed in MTX-injected mice. Licorice extracts positively regulated the expression of steroidogenesis genes suppressed by MTX, increased antioxidant enzymes (glutathione peroxidase, reduced glutathione, and catalase) and reduced biomarker of oxidative stress (testicular malondialdehyde) and inflammatory cytokines (IL-1 and -6). Moreover, reduction in testicular tissue immunoreactivity to Bcl-2-associated X protein and cyclogenase-2. In conclusion, licorice extract mitigated the toxic effects of MTX-induced testicular dysfunction at biochemical, molecular, and cellular levels.