Zinc citrate-coated whey protein nanoparticles alleviate kidney damage and the disturbances in inflammatory gene expression in rats.

This work was conducted to synthesize whey protein nanoparticles (WPNPs) for the coating of zinc citrate (Zn CITR) at three levels and to study their protective role against CCl4 -induced kidney damage and inflammatory gene expression disorder in rats. Seventy male Sprague-Dawley rats were divided into seven groups and treated orally for 4 weeks as follows; the control group, the group treated twice a week with CCl4 (5 mL/kg b.w), the groups received CCl4 plus WPNPs (300 mg/kg b.w); the group received 50 mg/kg b.w of Zn CITR or the three formulas of Zn CITR-WPNPs at low, medium and high doses (LD, MD, and HD). Blood and kidney samples were collected for different assays and histological analyses. The fabricated particles were semispherical, with an average size of 160 ± 2.7, 180 ± 3.1, and 200 ± 2.6 nm and ζ potential of -126, -93, and -84 mV for ZN CITR-WPNPs (LD), Zn CITR-WPNPs (MD), and ZN CITR-WPNPs (HD), respectively. CCl4 significantly increased (p ≤ 0.05) kidney function indices, oxidative stress markers, messenger RNA expression of transforming growth factor-ß1, interleukin (IL)-1ß, IL-10, IL-6, inducible nitric oxide synthase, and tumor necrosis factor-α and significantly decreased (p ≤ 0.05) renal superoxide dismutase, catalase, and glutathione peroxidase along with the histological changes in the kidney tissues. WPNPs, Zn CITR, and Zn CITR loaded WPNPS showed a protective effect against these complications and Zn CITR-WPNPs (LD) was more effective. WPNPs can be used effectively for coating Zn CITR at a level of 7 mg/g WPNPs to be used as a supplement for the protection of the kidney against different toxicants to enhance immunity and avoid harm of excess Zn.

Screening of the phytochemical constituents of Teucrium polium extract and evaluation of their prophylactic role against the oxidative damage and cytotoxicity of Aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is common carcinogen causing acute and chronic hepatocyte injuries. This study aimed to determine the bioactive components of Teucrium polium methanolic extract (TPE) and to evaluate their protective role against AFB1-induced oxidative damage, cytotoxicity, and genotoxicity in rats. Six groups of male albino rats were treated orally for 4 weeks including the control group, the ِAFB1-treated group (80 µg/kg b.w.), the groups treated with low (LD) or high (HD) dose TPE (50 or 100 mg/kg b.w.), and the groups treated with AFB1 plus TEP (LD) or TPE (HD). Blood and serum samples were collected for different assays. The GC-MS identified 34 compounds, the major compounds were pinene, germacrene D, α-cadinol, α-thujene, epi-bicyclosesquiphellandrene, and limonene. Animals that received AFB1 showed significant changes in all indicators of oxidative stress, biochemistry, cytokines, MNPCEs, comet tail formation in bone marrow, mRNA expression of inflammatory-related genes, Nrf2, and iNOS beside histological changes in the liver. TPE at the two doses tested showed insignificant changes in all tested parameters. The extract could normalize most of these parameters and the hepatic structure in AFB1-treated animals in a dose-dependent fashion. therefore, we concluded that TPE supplementation is effective for protection against AFB1 in endemic areas.

Corrigendum to "Biochemical and pharmacological prospects of citrus sinensis peel" [Heliyon 8, (8), (August 2022), e09979].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09979.].

Curcumin nanoemulsion counteracts hepatic and cardiac complications associated with high-fat/high-fructose diet in rats.

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10 mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.

Biochemical and pharmacological prospects of Citrus sinensis peel.

Gastric ulcer and hepatotoxicity due to irrational drug overuse are two of the most serious conditions associated with inflammation and oxidative stress that affect the digestive system. This study aimed to experimentally evaluate the hepatoprotective/gastroprotective effects of aqueous and butanol citrus peel extracts and hesperidin in rat models of ulcer and hepatotoxicity. Acute toxicity study was performed for determining the safe dose of citrus extracts to analyze efficacy. In the experiments on hepatoprotective and gastroprotective effects, rats were classified into nine groups in each experiment: (1) negative control, (2) positive control hepatotoxic model with paracetamol (640 mg/kg)/gastric ulcer model:ethanol 70% (1 ml), (3)reference hepatoprotective:silymarin (25 mg/kg)/gastroprotective:ranitidine (50 mg/kg), and (4-9) groups treated for 2 weeks before induction of each disease with either citrus aqueous or butanol extracts or hesperidin (125-250 mg/kg). Drugs, ethanol, or tested compounds were administered orally. The levels of biochemical parameters, such as AST, ALT, NO, MDA, CRP, and ILß6, were significantly reduced, but CAT level was increased. Postmortem examination of liver and stomach tissues of treated animals revealed marked improvement compared with positive control animals. Hesperidin exerted the best hepatoprotective, antioxidant, anti-inflammatory, and gastroprotective effects, followed by butanol and then aqueous citrus peel extracts.

Costus speciosus extract protects against the oxidative damage of zearalenone via modulation of inflammatory cytokines, Nrf2 and iNOS gene expression in rats.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that induces severe health disturbances in humans and animals. This study aimed to determine the bioactive compounds in Costus speciosus extract (CSE) using GC-MS and evaluate its protective capability against ZEN-induced oxidative damage, genotoxicity, and cytotoxicity in rats. Six groups of male Sprague Dawley rats were treated orally for 15 days including the control group, CSE-treated groups at low (200 mg/kg b. w) or high (400 mg/kg b. w) dose, ZEN-treated group (40 µg/kg b. w), and the groups treated with ZEN plus the low or the high dose of CSE. Blood and tissue samples were collected for different assays and pathological analyses. The results of GC-MS indicated the identification of 6 compounds and Azulene was the major. Animals that received ZEN showed severe disturbances in serum biochemical, cytokines, oxidative stress indicators, mRNA expression of iNOS, Nrf2, and inflammatory-related genes. ZEN also increased micronucleated polychromatic erythrocytes (MNPCEs) and comet tail formation in bone marrow cells along with the disturbances in the histological architecture of the liver and kidney. Co-administration of CSE plus ZEN could normalize the majority of the tested parameters and the histological picture at a dose as low as 200 mg/kg b. w. Therefore, CSE protects against ZEN toxicity via its antioxidant activity, modulation of iNOS, inflammatory-related genes, and the Nrf2 pathway and it could be used in the endemic regions.

A comparative study between curcumin and curcumin nanoemulsion on high-fat, high-fructose diet-induced impaired spermatogenesis in rats.

OBJECTIVES: Curcumin is a promising nutraceutical with reported diverse therapeutic properties, but of limited oral bioavailability. The current manuscript investigates the role of encapsulation of curcumin in nanoemulsion form in counteracting the adverse effect of chronic ingestion of a high-fat high-fructose diet (HFHF) by juvenile male rats regarding testicular abnormalities and declined spermatogenesis. METHODS: Curcumin nanoemulsion was administered orally to Wistar rats at a dose of 5 or 10 mg/kg and compared with curcumin powder, followed by a pharmacological and histological assessment. KEY FINDINGS: Results demonstrated that curcumin nanoemulsion was superior to curcumin powder, particularly in enhancing the percentage progressive motility of spermatozoa, normalization of essential and non-essential amino acids in semen, normalization of serum leptin and testosterone levels, as well as normalization of oxidative and nitrosative parameters. It was also proven to reduce testicular DNA fragmentation, while elevating testicular cellular energy. In addition, curcumin nanoemulsion administered at a dose of 10 mg/kg induced the highest level of spermatogenesis, delineated by histological examination of the seminiferous tubules. CONCLUSIONS: It can be concluded that curcumin nanoemulsion administered at a dose of 10 mg/kg successfully ameliorates the adverse effects of a HFHF on spermatogenesis.

Assessment of the protective effect of yeast cell wall ß-glucan encapsulating humic acid nanoparticles as an aflatoxin B1 adsorbent in vivo.

This study aimed to assess the protective effect of encapsulating humic acid-iron complexed nanoparticles (HA-Fe NPs) inside glucanmannan lipid particles (GMLPs) extracted from yeast cell wall against aflatoxin B (AFB1 ) toxicity in vivo. Four groups of male Sprague-Dawley rats were treated orally for 2 weeks included the control group, AFB1 treated group (80 µg/kg b.w); GMLP/HA-Fe NPs treated group (0.5 mg/kg b.w), and the group treated with AFB1 plus GMLP/HA-Fe NPs. GMLPs are empty 3-4 micron permeable microspheres that provide an efficient system for the synthesis and encapsulation of AFB1 -absorbing nanoparticles (NPs). Humic acid nanoparticles (HA-NPs) were incorporated inside the GMLP cavity by complexation with ferric chloride. In vivo study revealed that AFB1 significantly elevated serum alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid, urea, cholesterol, triglycerides, LDL, malondialdehyde, and nitric oxide. It significantly decreased total protein, high-density lipoprotein, hepatic and renal CAT and glutathione peroxidase content and induced histological changes in the liver and kidney (p ≤ 0.05). The coadministration of the synthesized formulation GMLP/HA-Fe NPs with AFB1 has a protective effect against AFB1 -induced hepato-nephrotoxicity, oxidative stress and histological alterations in the liver and kidney.

Natural products based crown ethers: synthesis and their anticancer potential.

Natural products based novel crown ethers have been prepared by employing biologically active natural structures including tetrahydroisoquinoline, chrysin and biochanin-A as the side arms. The resulting crown scaffolds were evaluated for their anticancer potential against two cancer cell lines i.e. NCI-H460 (non-small lung carcinoma), MCF-7 (breast adenocarcinoma). The comparative study showed that the addition of crown scaffold put marked effects on antiproliferative profile of parent natural precursors and is significant for lung carcinoma in particular. Biochanin-A derived crown ether showed three (03) folds higher antiproliferative activity (IC50 = 6.08 ± 0.07 µM) against lung carcinoma as compared to standard drug cisplatin (IC50 = 19.00 ± 1.24 µM). Cytotoxic trends for NIH-3T3 cell lines were also examined and found reduced as compared to parent natural structures. Hence, these findings could open a new pathway towards developing effective carcinostatic drugs.HIGHLIGHTSFour natural products based novel crown ethers have been developed.Comparative antiproliferative screening of crown ethers and natural precursors.Addition of crown showed marked effects on anticancer profile of natural products.Crown formation is significant for lung carcinoma potential in particular.Biochanin-A derived crown ether found three folds more active than standard drug.

Synthesis of encapsulated fish oil using whey protein isolate to prevent the oxidative damage and cytotoxicity of titanium dioxide nanoparticles in rats.

Fish oil exhibited several beneficial effects on human health; however, its applications face several challenges such as its effects on the organoleptic properties of food and its susceptibility to oxidation. Titanium dioxide NPs (TiO2-NPs) are utilized widely in pharmaceutical and food applications although there are some reports about their oxidative damage to living organisms. The current work was undertaken to identify fatty acids content in mullet fish oil, encapsulation, and characterization of the oil, and to assess the protective efficiency of the encapsulated mullet fish oil (EMFO) against the oxidative damage and genotoxicity of TiO2-NPs in rats. Sixty female Sprague-Dawley rats were distributed to 6 groups and treated for 21 days included the control group; TiO2-NPs-treated group (50 mg/kg b.w); the groups treated with EMFO (50 or 100 mg/kg b.w) and the groups received TiO2-NPs plus EMFO at the low or high dose. Samples of blood, liver, and kidney were taken for different assays and histological studies. The GC-FID analysis showed that a total of 14 different fatty acids were found in Mullet fish oil included 41.4% polyunsaturated fatty acids (PUFAs), 31.1% monounsaturated fatty acids (MUFAs), and 25.1% saturated fatty acids (SFAs). The structure of EMFO was spherical with an average diameter of 234.5 nm and a zeta potential of -6.24 mV and was stable up to 10 days at 25 °C with EE of 81.08%. The PV of EMFO was decreased at 5 days then increased at 15 days; however, TBARS was increased throughout the storage time over 15 days. The biological evaluation showed that TiO2-NPs disturb the hepato-nephro functions, lipid profile, inflammatory cytokines, oxidative stress markers, antioxidant enzymes activity, and their corresponding gene expression along with severe pathological alterations in both hepatic and renal tissue. Co-administration of EMFO induced a strong antioxidant role, and the high level could normalize the majority of the parameters tested and the histological picture of the hepatic and renal tissues. These results pointed out that the encapsulation technology enhances the protective role of EMFO against oxidative stress and genotoxicity of TiO2-NPs through the prevention of ω-3 PUFAs oxidation and controlling their release.

Nanoencapsulation of basil essential oil alleviates the oxidative stress, genotoxicity and DNA damage in rats exposed to biosynthesized iron nanoparticles.

The application of essential oils in food and pharmaceutical sectors face several challenges due to their sensitivity to oxidation process. Additionally, the biosynthesis of nanometals is growing rapidly; however, the toxicity of these particles against living organisms did not well explore yet. This study aimed to determine the bioactive compounds in basil essential oil (BEO) using GC-MS, to encapsulate and characterize BEO and to evaluate its protective role against the oxidative stress and genotoxicity of biosynthesized iron nanoparticles (Fe-NPs) in rats. Six groups of male Sprague-Dawley rats were treated orally for 4 weeks included the control group, Fe-NPs-treated group (100 mg/kg b.w.); EBEO-treated groups at low (100 mg/kg b.w.) or high (200 mg/kg b.w.) dose and the groups treated with Fe-NPs plus the low or the high dose of EBEO. The GC-MS analysis revealed the identification of 48 compounds and linalool was the major compound. The average sizes and zeta potential of the synthesized Fe-NPs and EBEO were 60 ± 4.76 and 120 ± 3.2 nm and 42.42 mV and -6.4 mV, respectively. Animals treated with Fe-NPs showed significant increase in serum biochemical analysis, oxidative stress markers, cytokines, lipid profile, DNA fragmentation and antioxidant enzymes and their gene expression and severe changes in the histology of liver and kidney tissues. Administration of Fe-NPs plus EBEO alleviated these disturbances and the high dose could normalize most of the tested parameters and improved the histology of liver and kidney. It could be concluded that caution should be taken in using the biosynthesized metal nanoparticles in different application. EBEO is a potent candidate to protect against the hazards of metal nanoparticles and can be applied in food and medical applications.

Bioactive phytochemicals from Salvia officinalis attenuate cadmium-induced oxidative damage and genotoxicity in rats.

This study was conducted to identify the bioactive phytochemicals in Salvia officinalis essential oil, to determine the polyphenols in the aqueous extract (SOE), and to evaluate their protective role against cadmium (Cd)-induced oxidative damage and genotoxicity in rats. Six groups of female rats were treated orally for 2 weeks including the control group, CdCl2-treated group, SOE-treated groups at low or high dose (100 and 200 mg/kg b.w), and CdCl2 plus SOE-treated groups at the two doses. The GC-MS analysis identified 39 compounds; the main compounds were 9-octadecenamide, eucalyptol, palmitic acid, and oleic acid. However, the HPLC analysis showed 12 polyphenolic compounds and the majority were coumaric acid, chlorogenic acid, coffeic acid, catechin, vanillin, gallic acid, ellagic acid, and rutin. In the biological study, rats received CdCl2 displayed severe disturbances in liver and kidney indices alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP), total bilirubin (T. Bil), direct bilirubin (D. Bil), creatinine, uric acid, and urea, lipid profile, tumor necrosis factor-alpha (TNF-α), alpha-fetoprotein (AFP) and CEA), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), gene expressions, DNA fragmentation, and histological alterations in the liver and kidney tissue. SOE showed a potent antioxidant and mitigated these alterations in serum and tissue. Moreover, the high dose succeeded to normalize most of the tested parameters and histological features. It could be concluded that S. officinalis is a promising source for bioactive compounds with therapeutic benefits against environmental toxicants.

Elimination of oxidative stress and genotoxicity of biosynthesized titanium dioxide nanoparticles in rats via supplementation with whey protein-coated thyme essential oil.

The green synthesis of metal nanoparticles is growing dramatically; however, the toxicity of these biosynthesized particles against living organisms is not fully explored. Therefore, this study was designed to synthesize and characterize TiO2-NPs, encapsulation and characterization thyme essential oil (ETEO), and determination of the bioactive constituents of ETEO using GC-MS and evaluate their protective role against TiO2-NPs-induced oxidative damage and genotoxicity in rats. Six groups of rats were treated orally for 30 days including the control group, TiO2-NPs (300 mg/kg b.w)-treated group, ETEO at low (50 mg/kg b.w) or high dose (100 mg/kg b.w)-treated groups, and TiO2-NPs plus ETEO at the two doses-treated groups. Blood and tissues were collected for different assays. The GC-MS results indicated the presence of 21 compounds belonging to phenols, terpene derivatives, and heterocyclic compounds. The synthesized TiO2-NPs were 45 nm tetragonal particles with a zeta potential of -27.34 mV; however, ETEO were 119 nm round particles with a zeta potential of -28.33 mV. TiO2-NPs administration disturbs the liver and kidney markers, lipid profile, cytokines, oxidative stress parameters, the apoptotic and antioxidant hepatic mRNA expression, and induced histological alterations in the liver and kidney tissues. ETEO could improve all these parameters in a dose-dependent manner. It could be concluded that ETEO is a promising candidate for the protection against TiO2-NPs and can be applied safely in food applications.

Nanoencapsulation of thyme essential oil: a new avenue to enhance its protective role against oxidative stress and cytotoxicity of zinc oxide nanoparticles in rats.

Although the green synthesis of nanometals is eco-friendly, the toxicity or safety of these biosynthesized nanoparticles in living organisms is not fully studied. This study aimed to evaluate the potential protective role of encapsulated thyme oil (ETO) against zinc oxide nanoparticles (ZnO-NPs). ETO was prepared using a mixture of whey protein isolate, maltodextrin, and gum Arabic, and ZnO-NPs were synthesized using parsley extract. Six groups of male Sprague-Dawley rats were treated orally for 21 days which included the control group, ZnO-NP-treated group (25 mg/kg body weight (b.w.)), ETO-treated groups at low or high dose (50, 100 mg/kg b.w.), and the groups that received ZnO-NPs plus ETO at the two tested doses. Blood and tissue samples were collected for different assays. The results showed that carvacrol and thymol were the major components in ETO among 13 compounds isolated by GC-MS. ZnO-NPs were nearly spherical and ETOs were round in shape with an average size of 38 and 311.8 nm, respectively. Administration of ZnO-NPs induced oxidative stress, DNA damage, biochemical, ctyogentical, and histological changes in rats. ETO at the tested doses alleviated these disturbances and showed protective effects against the hazards of ZnO-NPs. It could be concluded that encapsulation of thyme oil using whey protein isolate, maltodextrin, and gum Arabic improved the antioxidant properties of ETO, probably possess synergistic effects, and can be used as a promising tool in pharmaceutical and food applications.

Matlodextrin-cinnamon essential oil nanoformulation as a potent protective against titanium nanoparticles-induced oxidative stress, genotoxicity, and reproductive disturbances in male mice.

Recently, bio-nanofabrication becomes one of the widest methods for synthesizing nanoparticles (NPs); however, there is scanty literature exploring the toxicity of these green NPs against living organisms. This study aimed to evaluate the potential protective role of encapsulated cinnamon oil (ECO) against titanium oxide nanoparticle (TiO2NP)-induced oxidative stress, DNA damage, chromosomal aberration, and reproductive disturbances in male mice. Sixty male Balb/c mice were distributed into six groups treated orally for 3 weeks and included control group, TiO2NP-treated group (25 mg/kg b.w), ECO at low or high dose-treated groups (50 or 100 mg/kg b.w), and the groups that received TiO2NPs plus ECO at a low or high dose. The results of GC-MS revealed the isolation of 21 compounds and the majority was cinnamaldehyde. The average size zeta potential of TiO2NPs and ECO were 28.9 and 321 nm and -33.97 and -17.35 mV, respectively. TiO2NP administration induced significant changes in liver and kidney function, decreased antioxidant capacity, and increased oxidative stress markers in liver and kidney, DNA damage in the hepatocytes, the number of chromosomal aberrations in the bone marrow and germ cells, and sperm abnormalities along with histological changes in the liver, kidney, and testis. Co-administration of TiO2NPs and ECO could alleviate these disturbances in a dose-dependent manner. It could be concluded that ECO is a promising and safe candidate for the protection against the health hazards of TiO2NPs.

Evaluation of carcinogenic activities and sperm abnormalities of Gram-negative bacterial metabolites isolated from cancer patients after subcutaneous injection in albino rats.

Microbial pathogens drive tumorigenesis in 20% of cancer cases, so the present study is aimed to evaluate the carcinogenic activities, sperm abnormalities and other dangerous effects of the subcutaneous injection of extracts obtained from various clinical Gram-negative bacteria derived from cancer patients using albino rats. We isolated, identified and extracted of their secondary metabolites of carbapenem resistant Gram-negative bacteria derived from cancer patients. Various methods have been used to determine hepatotoxicity, nephrotoxicity, tumorigenesis, inflammatory and sperm abnormalities in the albino rats injected with extracts. In comparison with the normal animals group, all extracts induced hepatotoxicity which was evidenced by the significant elevation in the activity of the serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and alkaline phosphatase; also, nephrotoxicity that was indicated through the marked increase in the serum urea and creatinine levels; tumorigenesis was achieved from the sharp elevation in serum levels of alpha fetoprotein, carcinoembryonic antigen and lactate dehydrogenase values as tumor markers; as well as severe inflammatory characteristics were monitored from the marked raise of tumor necrosis factor alpha and interleukin-1beta. Furthermore, the proportion of micronuclei in polychromatic erythrocytes and sperm abnormalities were statistically significant in all groups compared to control group. Various kinds of head abnormalities and coiled tail were noted. Histopathological examination of hepatic tissue came in line with the biochemical and cytological findings. It could conclude that the extracts of Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 were able to initiate cytotoxicity and tumorigenesis in rats.

Nifuroxazide suppresses UUO-induced renal fibrosis in rats via inhibiting STAT-3/NF-κB signaling, oxidative stress and inflammation.

The current work explored the influences of nifuroxazide, an in vivo inhibitor of signal transducer and activator of transcription-3 (STAT-3) activation, on tubulointerstitial fibrosis in rats with obstructive nephropathy using unilateral ureteral obstruction (UUO) model. Thirty-two male Sprague Dawley rats were assigned into 4 groups (n = 8/group) at random. Sham and UUO groups were orally administered 0.5% carboxymethyl cellulose (CMC) (2.5 mL/kg/day), while Sham-NIF and UUO-NIF groups were treated with 20 mg/kg/day of NIF (suspended in 0.5% CMC, orally). NIF or vehicle treatments were started 2 weeks after surgery and continued for further 2 weeks. NIF treatment ameliorated kidney function in UUO rats, where it restored serum creatinine, blood urea, serum uric acid and urinary protein and albumin to near-normal levels. NIF also markedly reduced histopathological changes in tubules and glomeruli and attenuated interstitial fibrosis in UUO-ligated kidneys. Mechanistically, NIF markedly attenuated renal immunoexpression of E-cadherin and α-smooth muscle actin (α-SMA), diminished renal oxidative stress (↓ malondialdehyde (MDA) levels and ↑ superoxide dismutase (SOD) activity), lessened renal protein expression of phosphorylated-STAT3 (p-STAT-3), phosphorylated-Src (p-Src) kinase, the Abelson tyrosine kinase (c-Abl) and phosphorylated nuclear factor-kappaB p65 (pNF-κB p65), decreased renal cytokine levels of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and monocyte chemoattractant protein-1 (MCP-1) and reduced number of cluster of differentiation 68 (CD68) immunolabeled macrophages in UUO renal tissues, compared to levels in untreated UUO kidneys. Taken together, NIF treatment suppressed interstitial fibrosis in UUO renal tissues, probably via inhibiting STAT-3/NF-κB signaling and attenuating renal oxidative stress and inflammation.

Dasatinib mitigates renal fibrosis in a rat model of UUO via inhibition of Src/STAT-3/NF-κB signaling.

This research aimed to investigate the reno-protective impact of the tyrosine kinase inhibitor dasatinib (DAS) against renal fibrosis induced by unilateral ureteral obstruction (UUO) in rats. DAS administration improved renal function and mitigated renal oxidative stress with paralleled reduction in the ligated kidney mass index, significant retraction in renal histopathological alterations and suppression of renal interstitial fibrosis. Nevertheless, DAS administration attenuated renal expression of phosphorylated Src (p-Src), Abelson (c-Abl) tyrosine kinases, nuclear factor-kappaB (NF-κB) p65, and phosphorylated signal transducer and activator of transcription-3 (p-STAT-3)/STAT-3 with paralleled reduction in renal contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1). DAS diminished interstitial macrophage infiltration and decreased renal profibrotic transforming growth factor-ß1 (TGF-ß1) levels and suppressed interstitial expression of renal α-smooth muscle actin (α-SMA) and fibronectin. Collectively, DAS slowed the progression of renal interstitial fibrosis, possibly via attenuating renal oxidative stress, impairing Src/STAT-3/NF-κB signaling, and reducing renal inflammation.

Nematicidal activity of oleanolic acid derivatives on Meloidogyne incognita.

In this study, oleanolic acid and its derivatives were studied for their invivo nematicidal activity against root-knot nematode (RKN) Meloidogyne incognita. A series of C-28-oleanolates including five new (5, 7-10) and seven known (1-4, 6, 11, 12) compounds were synthesised and their nematicidal activity was determined and compared with the standard nematicide furadan for the first time. The structures of the compounds were elucidated through 1H NMR, 13C NMR and EIMS. Compounds 4, 5, 7, 8 and 10 showed ∼ 90% inhibition of RKN at 0.125% concentration after 72 h showing their potential use in nematicidal control.