Behavioral, biochemical, histopathological evaluation and gene expression of brain injury induced by nanoceria injected intranasal or intraperitoneal in mice.

Background: Nanotechnology has shown a remarkable progress nevertheless, there is a growing concern about probable neurotoxic and neurodegenerative effects due to NPs exposure. Various toxicological and epidemiological studies reported that the brain is a main target for ultrafine particles. Brain inflammation is considered as a possible mechanism that can participate to neurotoxic and neurodegenerative effects. Whether nanoparticles (NPs) may produce neurotoxicity and promote neurodegenerative is largely unstudied. The present study was done to investigate whether intranasal and intra-peritoneal exposure to cerium oxide nanoparticles (CeO2NPs, nanoceria (NC)) could cause neurotoxicity and neurodegenerative changes in the brain tissue through conducting some behavioral tests, biochemical evaluation, histopathological examinations of brain hippocampus and gene expressions. Method: Fifteen mice were separated into 3 equal groups. In group (I) "control group", mice were received distilled water orally and kept as a control group. Mice in the group (II) "NC I/P group" were injected i.p with cerium oxide nanoparticles at a dose of 40 mg/kg b.wt, twice weekly for 3 weeks. In group (III) "NC I/N group" mice were received nanoceria intranasally (40 mg/kg b.wt), twice weekly for 3 weeks. Results: Exposure to nanceria resulted in oxidative damage in brain tissue, a significant increase in malondialdehyde (MDA) and acetylcholinestrase (AchE) levels, significant decrease in reduced glutathione (GSH) concentration, upregulation in the apoptosis-related genes (c-Jun: c-Jun N-terminal kinases (JNKs), c-Fos: Fos protooncogene, AP-1 transcription factor subunit, c-Myc: c-myelocytomatosis oncogene product or MYC protooncogene, bHLH transcription factor), locomotor and cognitive impairment in mice but the effect was more obvious when nanoceria adminstred intraperitoneally. Conculsion: Nanoceria cause oxidative damage in brain tissue of mice when adminstred nanoceria intraperitoneally more than those received nanoceria intranasal.

Eltroxin and Hesperidin mitigate testicular and renal damage in hypothyroid rats: amelioration of oxidative stress through PPARγ and Nrf2/HO-1 signaling pathway.

BACKGROUND: Thyroid hormones (THs) regulate growth, development and function of different tissues. Hypothyroidism is a common clinical disorder characterized by deficiency in THs and adversely affects the development and functions of several organs. This work aimed to investigate the ameliorative effect of eltroxin (ELT), a hypothyroidism medication, and hesperidin (HSP), a flavonoid, against testicular and renal toxicity in hypothyroid rats. Twenty-four rats were divided into four groups and treated orally for 12 weeks. Group I (control), group II (hypothyroidism) received 20 mg/kg carbimazole (CBZ), group III received CBZ and 0.045 mg/kg ELT, and group IV received CBZ and 200 mg/kg HSP. RESULTS: CBZ administration induced biochemical and histopathological changes in testis and kidney. Co-administration of ELT or HSP significantly (P < 0.05) ameliorated THs, reduced urea and creatinine while raised follicle stimulating hormone (FSH), Luteinizing hormone (LH), and testosterone in serum. Testicular and renal malondialdehyde level as a lipid peroxidation indicator, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly (P < 0.05) decreased while glutathione content, glutathione peroxidase, and glutathione-s-transferase activities were significantly (P < 0.05) increased. The histopathological changes were also diminished. Decreased mRNA and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor gamma(PPARγ) in hypothyroid rats were up-regulated after ELT or HSP treatment. CONCLUSIONS: ELT and HSP showed antioxidant and anti-inflammatory effects against CBZ-induced testicular and renal toxicity, and these effects may be promoted via activating Nrf2/HO-1 and PPARγ signaling pathways.

The effects of TiO2, ZnO, IONs and Al2O3 metallic nanoparticles on the CYP1A1 and NBN transcripts in rat liver.

Introduction: Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al2O3NPs on the mRNA expression level of CYP 1A1 and NBN in the rat liver. Materials and Methods: Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b.wt/day), ZnONPs (340 mg/Kg b.wt/day), IONs (200 mg/kg b.wt/day) and Al2O3NPs (100 mg/Kg b.wt/day) and a fifth group served as a control group. Rresults: The mRNA level of CYP 1A1 and NBN showed up-regulation in all the NPs-treated groups relative to the control group. ZnONPs group recorded the highest expression level while the TiO2NPs group showed the lowest expression level transcript. Conclusion:The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide, iron oxide nanoparticles and titanium dioxide, respectively.

Pathological assessment and tissue tropism of two different Egyptian infectious bronchitis strains.

Avian infectious bronchitis is one of the most common viral infections in chickens affecting all ages. The tropism of infectious bronchitis virus (IBV) strains became broader and more variable posing major implications for the effective control of IBV infection. In this study, two IBV viruses representing classic and variant strains were inoculated intranasally into day-old SPF chicks (105 EID50/0.2 ml/bird). Clinical signs were observed for 15 days post-infection (DPI). Five chicks from each group were euthanized at 2, 4, 6, 8, 10, 12, and 15 DPI for histopathology and virus antigen detection by IHC and quantitative rRT-PCR. Results revealed that both classic and variant IBV strains induced mild clinical signs with no mortalities and fewer various histopathological lesions in infected SPF chickens. Although the viruses were detected by rRT-PCR up to 12 DPI, the affected tissues showed regeneration after 10 DPI with IHC revealing no IBV antigen. In summary, no differences were found in the behaviour of both IBV isolates in chickens. The broad tissue tropism for both IBV strains as indicated by viral antigen detection in various organs with no clinical or gross lesion suggest that the main cause of death in IBV infection under field conditions occurs as a result of complication with secondary infections rather single IBV infection. Due to positive immunostaining in the bursa, it is thought that IBV infection has immunosuppressive consequences, hence further study is required to validate this impact.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation.

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body's antioxidant defense system, reducing inflammation, and suppressing apoptosis.

The prevalence and molecular detection of bovine cysticercosis and its impact on slaughtered cattle in Egypt.

Cysticercus bovis is the metacestode of the commonly defined foodborne cestode, Taenia saginata. It infects heart, masseter muscles and other muscular sites of cattle causing bovine cysticercosis. So, a retrospective study using archival documents from authorized agencies is done during the period of 2018-2020 with estimating economic losses. Cysts were collected from municipal Beni-Suef and Basatin abattoirs. Molecular approach including cPCR and sequencing analysis is used to prove the species. The prevalence was 0.34% in Beni-Suef abattoir and 5.70% in Basatin abattoir including heads, hearts or all carcasses condemned. Among 27 provinces surveyed, the highest prevalence was recorded in Aswan followed by Cairo, Suez and Red Sea. Moreover, 19 provinces (Cairo, Alexandria, Suez, Dakahlia, Sharkia, Qalyobia, Kafrelsheikh, Gharbia, Menofiya, Ismailia, Giza, Beni-Suef, Assiut, Sohag, Qena, Aswan, Red Sea, South Sinai and El-Wadi El-Gadid) recorded bovine cysticercosis in 2018, 2019 and 2020. On the other hand, Luxor and North Sinai had no infections. The percentages of condemnation among slaughtered cattle were 1.38, 1.49 and 0.87% in 2018, 2019 and 2020, respectively. Condemnations significantly varied among north, middle and south districts of Egypt, and also varied annually. Molecularly, a diagnostic band at an amplicon size 253 bp targeting the COI gene specific for Cycticercus bovis was revealed. The obtained sequences showed 100% identity with the different Taenia saginata COI GB sequence isolates in many countries worldwide. The phylogenetic analysis method showed that the obtained sequences originating from the same clade of Taenia saginata GB isolates globally. Careful meat inspection as well as strict hygienic measures is recommended for both veterinarians and public.

Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.

Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar Rats via Suppressing the Oxidative Stress and Enhancing the Antioxidant Defense Mechanisms.

Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.

The Preventive Effects of Naringin and Naringenin against Paclitaxel-Induced Nephrotoxicity and Cardiotoxicity in Male Wistar Rats.

This study assessed the preventive properties of naringin and naringenin on paclitaxel-induced nephrotoxicity and cardiotoxicity in adult male Wistar rats. Intraperitoneal injection of paclitaxel 2 mg/kg body weight, two days/week on the 2nd and 5th days of each week, with or without oral administration of naringin and/or naringenin 10 mg/kg body weight every other day, was continued for six weeks. Treatment of rats with naringin and/or naringenin significantly reversed elevated serum creatinine, urea, and uric acid levels caused by paclitaxel, reflecting improved kidney function. Similarly, heart dysfunction induced by paclitaxel was alleviated after treatment with naringin and/or naringenin, as evidenced by significant decreases in elevated CK-MB and LDH activities. After drug administration, histopathological findings and lesion scores in the kidneys and heart were markedly decreased by naringin and/or naringenin. Moreover, the treatments reversed renal and cardiac lipid peroxidation and the negative impacts on antioxidant defenses via raising GSH, SOD, and GPx. The preventive effects of naringin and naringenin were associated with suppressing oxidative stress and reestablishing antioxidant defenses. A combination of naringin and naringenin was the most efficacious in rescuing organ function and structure.

Deltamethrin and Its Nanoformulations Induce Behavioral Alteration and Toxicity in Rat Brain through Oxidative Stress and JAK2/STAT3 Signaling Pathway.

Deltamethrin (DM) is the most powerful synthetic pyrethroid that has toxicity to the central nervous system and results in behavioral changes in both animals and humans. This effect is mediated by inducing alterations in the action of neurotransmitters and brain pathological changes. Nanocarrier encapsulated pesticides may decrease the toxicity of pesticides. Thus, this study aimed to determine the effect of an inorganic metal carrier (silica Nps) and polymeric capsule (chitosan Nps) of deltamethrin nano-formulations on antioxidant levels and oxidative stress in the brain and on behavior of the male albino rat. Sixty male albino rats were equally divided into four groups. Group I: control group; group II given DM liquefied in corn oil at 3.855 mg/kg BW; group III receiving silica-loaded deltamethrin (S/DM Nps) at 8.795 mg/kg BW; and group IV: given chitosan encapsulated deltamethrin (CS/DM Nps) at 30.44 mg/kg BW. All treatments were given orally for four weeks. Following this, behavioral tests were conducted to record locomotor activity, anxiety like behaviors, exploration, and the short memory of rats. In addition, brain antioxidant/oxidant, serum neurotransmitters such as acetylcholine esterase (AchE) and monoamine oxidase (MAO), JAK2 and STAT3 gene and proteins expression were measured. The DM group showed a highly significant elevation in malondialdehyde content, MAO, AchE, vascular endothelial growth factor (VEGF) levels, and the expression level of neurogenic genes, JAK2 and STAT3, in comparison with the control group. Both S/DM Nps and CS/DM Nps significantly decreased MAO, AchE, and VEGF compared with the DM group. Moreover, both S/DM Nps and CS/DM Nps significantly decreased the gene and proteins expression of JAK2 and STAT3 compared with the DM group. These alterations were evidenced by the deficiency in memory and learning behaviors that were accompanied by histopathological findings of the hippocampus and the cortex. It was concluded that the nano formulations containing DM induced less neurobehavioral toxicity than free DM. Additionally, the use of nanocarriers reduced the damage to health and the environment.

Therapeutic effect of mesenchymal stem cells on histopathological, immunohistochemical, and molecular analysis in second-grade burn model.

BACKGROUND AND AIM: Deleterious cutaneous tissue damages could result from exposure to thermal trauma, which could be ameliorated structurally and functionally through therapy via the most multipotent progenitor bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to induce burns and examine the effect of BM-MSCs during a short and long period of therapy. MATERIAL AND METHODS: Ninety albino rats were divided into three groups: group I (control); group II (burn model), the animals were exposed to the preheated aluminum bar at 100°C for 15 s; and group III (the burned animals subcutaneously injected with BM-MSCs (2×106 cells/ ml)); they were clinically observed and sacrificed at different short and long time intervals, and skin samples were collected for histopathological and immunohistochemical examination and analysis of different wound healing mediators via quantitative polymerase chain reaction (qPCR). RESULTS: Subcutaneous injection of BM-MSCs resulted in the decrease of the wound contraction rate; the wound having a pinpoint appearance and regular arrangement of the epidermal layer with thin stratum corneum; decrease in the area percentages of ADAMs10 expression; significant downregulation of transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), tumor necrotic factor-α (TNF-α), metalloproteinase-9 (MMP-9), and microRNA-21; and marked upregulation of heat shock protein-90α (HSP-90α) especially in late stages. CONCLUSION: BM-MSCs exhibited a powerful healing property through regulating the mediators of wound healing and restoring the normal skin structures, reducing the scar formation and the wound size.

Design, synthesis, biological assessment and in silico ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors.

A novel series of benzimidazole derivatives wherein 4-(methylsulfonyl) phenyl pharmacophore attached via its C-2 position was designed and synthesized. These compounds were evaluated in vitro as cyclooxygenase-1(COX-1)/cyclooxygenese-2(COX-2) inhibitors. Furthermore, the synthesized compounds were also in vivo evaluated for their anti-inflammatory activity and ulcerogenic liability. Examination of histopathological lesions was also performed to evaluate the cariogenic effect of most active compounds. In silico prediction of physicochemical properties, ADME, and drug-likeness profiles were also studied. Several compounds as 11b, 11k, 12b, and 12d showed selective inhibition to (COX-2) isozyme. Compound 11b showed the most potent (COX-2) inhibitory activity with (IC50 = 0.10 µM) and selectivity index (SI = 134); the tested compounds also have shown good anti-inflammatory activity. Regarding the ulcerogenic liability, compound 11b was also safest one (Ulcer Index) (UI = 0.83). The results of the molecular docking studies is closely related to the results of the in vitro COX-2 inhibitory activities.

New indomethacin analogs as selective COX-2 inhibitors: Synthesis, COX-1/2 inhibitory activity, anti-inflammatory, ulcerogenicity, histopathological, and docking studies.

New indomethacin analogs 4a-g, 5, 6, 8a, and 8b were synthesized to overcome the nonselectivity and ulcer liability of indomethacin. All newly synthesized compounds were more potent against cyclooxygenase 2 (COX-2; IC50 value range: 0.09-0.4 µÐœ) as compared with celecoxib (IC50 = 0.89 µÐœ). Compounds 4a, 4b, 4d, 5, and 6 showed the highest COX-2 selectivity index (SI range = 4.07-6.33) as compared with indomethacin (SI = 1.14) and celecoxib (SI = 3.52). Additionally, 4a, 4b, 4d, 5, and 7 showed good anti-inflammatory activity with edema inhibition (79.36-88.8%), relative to celecoxib (78.96%) and indomethacin (90.43%), after 5 h. Also, ulcerogenic effects and histopathological examination were assessed for the most potent analogs, 4b, 4d, 5, and 6, to determine their safety. The results can shed light on indomethacin analog 5 as a remarkable anti-inflammatory lead compound with a good safety profile (ulcer index = 10.62) close to the nonulcerogenic drug celecoxib (ulcer index = 10.53) and better than indomethacin (ulcer index = 18.50). Docking studies were performed in the COX-2 active site for the most active compounds, to test their selectivity and to confirm their mechanism of action.

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.

Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE2, TNF-α, IL-6 and histopathological study.

To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SO2NH2 in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib. Compounds 3b, 3c, 4b, 4c, 5b and 5c exhibited potent in vitro COX-2 inhibitory activity (IC50 = 0.039-0.065 µM). Trimethoxy derivatives 3c, 4c and 5c acquired superior COX-2 selectivity index values (SI = 297.67-317.95) and were 1.1 fold higher than celecoxib (SI = 282.22). The most active six compounds were evaluated for their in vivo anti-inflammatory activity and serum levels of PGE2, TNF-α and IL-6 in addition to their ulcerogenic liability and histopathological profile. At a dose of 50 mg/Kg, compounds 3c and 5c showed better anti-inflammatory activity (% edema inhibition = 29.209-42.643) than celecoxib (% edema inhibition = 28.694-40.114) at different time intervals and were less ulcerogenic (UI = 0.123 and 0.11 in sequent) than celecoxib (UI = 0.167). Also, they displayed potent inhibitory effect on the production of PGE2 (% inhibition = 81.042 and 82.724 in sequent) greater than celecoxib (% inhibition = 79.666). Compound 5c decreased rat serum concentrations of both TNF-α (% inhibition = 55.349) and IL-6 (% inhibition = 61.561) in a comparable or better activity to celecoxib as reference drug. Finally, docking poses of the most active compounds showed strong binding interactions and effective overall docking energy scores explaining their remarkable COX-2 inhibitory activity.

Nephroprotective Effect of Pleurotus ostreatus and Agaricus bisporus Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-κB, p53, Bcl-2, Bax and Bak.

This study was designed to assess the nephroprotective effects of Pleurotus ostreatus and Agaricus bisporus aqueous extracts and carvedilol on hyperoxaluria-induced urolithiasis and to scrutinize the possible roles of NF-κB, p53, Bcl-2, Bax and Bak. Phytochemical screening and GC-MS analysis of mushrooms' aqueous extracts were also performed and revealed the presence of multiple antioxidant and anti-inflammatory components. Hyperoxaluria was induced in Wistar rats through the addition of 0.75% (v/v) ethylene glycol in drinking water for nine weeks. The ethylene glycol-administered rats were orally treated with Pleurotus ostreatus and Agaricus bisporus aqueous extracts (100 mg/kg) and carvedilol (30 mg/kg) daily during the last seven weeks. The study showed that Pleurotus ostreatus, Agaricus bisporus and carvedilol all successfully inhibited ethylene glycol-induced histological perturbations and the elevation of serum creatinine, serum urea, serum and urinary uric acid, serum, urinary and kidney oxalate, urine specific gravity, kidney calcium, kidney NF-κB, NF-κB p65, NF-κB p50, p53, Bax and Bak expressions as well as serum TNF-α and IL-1ß levels. Moreover, the treatment decreased the reduction in urinary creatinine, urinary urea, ratios of urinary creatinine to serum creatinine and urinary urea to serum urea, Fex Urea and Bcl-2 expression in kidney. In conclusion, although Pleurotus ostreatus and Agaricus bisporus extracts and carvedilol all significantly inhibited the progression of nephrolithiasis and showed nephroprotective effects against ethylene glycol-induced kidney dysfunction, Pleurotus ostreatus and Agaricus bisporus seemed to be more effective than carvedilol. Moreover, the nephroprotective effects may be mediated via affecting NF-κB activation, extrinsic apoptosis and intrinsic apoptosis pathways.

The current prevalence and diversity of cystic echinococcosis in slaughtered animals in Egypt.

Cystic echinococcosis is a potential zoonotic helminthic disease affect a broad spectrum of mammals including humans worldwide. The economic impact of the disease interestingly requires updated gathering information on the prevalence in slaughtered animals. Accordingly, in the current study, 573 camels, 4300 sheep, and 1235 pigs were surveyed in four Egyptian municipal abattoirs. Among those, 62 (10.82%) camels, 33 (0.77%) sheep and 3 (0.24%) pigs had cystic echinococcosis in lungs, livers and spleen. The diversity of cysts revealed that positive-cystic echinococcosis animals from all species were detected in El-Basatin abattoir. In El-Monieb abattoir, sheep only were infected. In El-Waraa and Beni-Suef abattoirs, cysts were seen in camels only. Infected animals included both sexes. In camels, lungs were the most affected organs, while in sheep, livers were the most abundant. In pigs, hydatid cysts were detected only in lungs. Moreover, camel cysts were mostly large-sized (diameter > 10 cm) with smaller cysts are also recorded. In sheep, small-, moderately- and large-sized cysts were equally present. Cysts in pigs were large-sized. Camels showed a higher percentage of fertile cysts (46.77%; 29/62) followed by sheep (21.21%; 7/33). Calcified/degenerated cysts were less in camels (38.71%; 24/62) than in sheep (75.76%). Non-viable cysts were the less frequent in both species (14.52% in camels and 3.03% in sheep). All cysts recovered from pigs were fertile. In Egypt, governmental agencies and veterinary authorities are asked to potentially eradicate stray dogs (the main definitive host) and towards the proper hygienic disposal of infected offal in abattoirs to minimize the prevalence of cystic echinococcosis.

Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats.

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.

The Preventive Effects and the Mechanisms of Action of Navel Orange Peel Hydroethanolic Extract, Naringin, and Naringenin in N-Acetyl-p-aminophenol-Induced Liver Injury in Wistar Rats.

N-Acetyl-p-aminophenol (APAP) or acetaminophen is the most common drug ingredient worldwide. It is found in more than 600 different over-the-counter and prescription medicines. Its long-term and overdose use is highly toxic and may result in liver injury. Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of the navel orange peel hydroethanolic extract, naringin, and naringenin in APAP-induced hepatotoxicity in male Wistar rats. APAP was administered to male Wistar rats at a dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with the navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.), and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with the peel extract, naringin, and naringenin produced a significant decrease in the elevated serum AST, ALT, ALP, LDH, and GGT activities as well as total bilirubin and TNF-α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver lipid peroxidation and enhanced the liver GSH content and SOD, GST, and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the liver LPO, GSH content, and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic proapoptotic mediators p53, Bax, and caspase-3 and significantly upregulated the suppressed antiapoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver histopathological deteriorations that include hepatocyte steatosis, cytoplasmic vacuolization, hydropic degeneration, and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells' infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin, and naringenin may exert their hepatopreventive effects in APAP-administered rats via enhancement of the antioxidant defense system and suppression of inflammation and apoptosis.