Human Wharton's jelly-derived mesenchymal stromal stem cells preconditioned with valproic acid promote cell migration and reduce renal inflammation in ischemia/reperfusion injury by activating the AKT/P13K and SDF1/CXCR4 pathways.

OBJECTIVE: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. METHODS: 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. RESULTS: WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-ß1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. CONCLUSION: WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury.

Evaluation of chemical castration using intra-testicular injection of zinc gluconate into the testis of the male donkey versus surgical castration: antimullerian hormone as an endpoint marker.

BACKGROUND: Chemical castration of male animals is an alternative to surgical castration for inducing azoospermia, consequent sterility. Intra-testicular injection of zinc gluconate has been used for chemical castration in several animal species. However, its application to equine species, such as donkeys, has yet to be reported. This study aimed to evaluate the use of zinc gluconate for the chemical castration of male donkeys and to compare its effectiveness relative to routine surgical castration. For this purpose, investigations of serum testosterone and anti-Müllerian hormone levels, testicular ultrasonographic echogenicity, and histopathological findings were performed. METHODS: Fourteen clinically healthy adult male donkeys were randomly and equally divided into two groups. The donkeys in group I (n = 7) underwent surgical castration. The donkeys in group II (n = 7) received intra-testicular zinc gluconate injections. The donkeys were kept under close clinical observation for 60 days. Abnormalities in donkey behavior and gross alterations in the external genitalia were recorded daily. Serum testosterone and anti-Müllerian hormone (AMH) levels were measured 15 days before the start of the treatment and 15, 30, 45, and 60 days after treatment. The testicles of group II donkeys were evaluated ultrasonographically. At the end of the study, the testes were removed and histologically examined. RESULTS: Serum testosterone levels significantly declined compared to pre-castration levels in surgically castrated donkeys (group I), but donkeys exposed to chemical castration (group II) showed a non-significant reduction in testosterone levels. Donkeys in the surgical group had considerably lower serum AMH levels. In contrast, there was a non-significant (p > 0.05) increase in AMH levels in the chemical group compared with the pre-sterilization level. In addition, ultrasonographic examination revealed that the testicular echo-density had changed, as observed by a few scattered hyperechoic regions throughout the entire testis parenchyma. The histopathological investigation confirmed the presence of necrosis of the spermatogenic epithelium, increased thickness of the basement membrane of the seminiferous tubules, marked interstitial fibrosis, and shrinkage of the seminiferous tubules. Furthermore, syncytial giant cells were present in the lumen of seminiferous tubules and were associated with Sertoli cell vacuolation. Donkeys subjected to chemical castration (group II) had orchitis, as confirmed histopathologically. CONCLUSION: Intra-testicular injection of zinc gluconate resulted in histopathological and ultrasonographic testicular changes in adult male donkeys, which may affect their reproductive potential. However, it did not significantly alter serum testosterone or AMH levels, indicating that it cannot be used as a substitute for surgical castration in male donkeys.

The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows.

AIM: OvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow during the Ovsynch program for synchronization of estrus and its relation to the pregnancy rates in Holstein cows. MATERIALS AND METHODS: The experimental cows received an intramuscular dose of 10 µg of a GnRH analogue (G1), followed 7 days later with an intramuscular injection of synthetic prostaglandin F2α (P: PGF2α) analogue (500 µg cloprostenol sodium), and given a 10 µg, injection of the GnRH analogue (G2) i.m. 48 h after the PGF2α treatment, and the cows were bred 14-16 h after. Uterine and vaginal perfusion were investigated by performing transrectal Doppler ultrasonography of both the uterine and vaginal arteries in Holstein cows at different time points during the Ovsynch program to determine: peak systolic velocity (PSV), time-averaged maximum velocity (TAMV), the volume of blood flow (BFV), pulsatility index (PI), resistance index (RI), resistance impedance (S/D) and diameters of uterine (UA) and vaginal (VA) arteries. Steroid hormones were also assayed. Transrectal ultrasonography (TUS) was performed at 32 and 60 days to confirm the pregnancy per artificial insemination (P/AI). RESULTS: The uterine PSV, TAMV, and PV were greater at the time of the cloprostenol sodium and second GnRH injections (p<0.05) than at the time of the first GnRH injection. The vaginal PSV, PV were greater at the time of the cloprostenol sodium than at the time of the first and second GnRH injections (p<0.05). The receiver operating characteristic curve (ROC curve) indicated a high correlation between the uterine and vaginal blood flow and the rate of the pregnancy (p<0.05). The area under the ROC curve was 0.920 and 0.87 (p<0.05) for vaginal and uterine arteries respectively at time of G2. The serum levels of progesterone, estrogen and cortisol were correlated with the P/AI (p<0.05). The P/AI significantly decreased from 43.9 % at 32 d to 35.37 % at 60 d. CONCLUSION: These results indicate that noninvasive Doppler ultrasonography is a valid method to evaluate changes in the characteristics of uterine and vaginal blood flow in cows during the Ovsynch protocol. Furthermore, vaginal and uterine blood flow are two determinant factors for the higher conception rates in Holstein dairy cows.

Effects of Rosemary Oil (Rosmarinus officinalis) supplementation on the fate of the transplanted human olfactory bulb neural stem cells against ibotenic acid-induced neurotoxicity (Alzheimer model) in rat.

Rosemary oil (ROO) is known to have multiple pharmacological effects: it is an antioxidant, anti-inflammatory, and cytoprotective. In the present study, we examined the effects of ROO on Human olfactory bulb neuronal stem cells (hOBNSCs) after their transplantation into rats, with the ibotenic (IBO) acid-induced cognitive deficit model. After 7 weeks, cognitive functions were assessed using the Morris water maze (MWM). After two months blood and hippocampus samples were collected for biochemical, gene expression, and histomorphometric analyses. Learning ability and memory function were significantly enhanced (P < 0.05) after hOBNSCs transplantation and were nearly returned to normal in the treated group. The IBO acid injection was associated with a significant decline (P < 0.05) of total leukocyte count (TLC) and a significant increase (P < 0.05) in total and toxic neutrophils. As well, the level of IL-1ß, TNF-α CRP in serum and levels of MDA and NO in hippocampus tissue were significantly elevated (P < 0.05), while antioxidant markers (CAT, GSH, and SOD) were reduced (P < 0.05) in treated tissue compared to controls. The administration of ROO before or with cell transplantation attenuated all these parameters. In particular, the level of NO nearly returned to normal when rosemary was administrated before cell transplantation. Gene expression analysis revealed the potential protective effect of ROO and hOBNSCs via down-expression of R-ßAmyl and R- CAS 3 and R-GFAP genes. The improvement in the histological organization of the hippocampus was detected after the hOBNSCs transplantation especially in h/ROO/hOBNSCs group.

Chitosan attenuated the neurotoxicity-induced titanium dioxide nanoparticles in brain of adult rats.

In the current study, we aimed to investigate the neurotoxic effect of oral titanium dioxide nanoparticles (TiO2 NPs) as well as the possible neuroprotective effect of carboxymethyl chitosan in adult rats for 14 days. The results revealed that TiO2 NPs inhibited the activity of the acetylcholine esterase enzyme and the levels of serotonin, dopamine, and norepinephrine neurotransmitters. Additionally, it induced neuro-oxidative stress and neuroinflammation via an elevation in MDA levels and IL-6, while GSH concentration, as well as GPx and GST activities, were decreased. TiO2 NPs induced neuronal apoptosis through upregulation of the expression of caspase-8 and -9 that was further confirmed by increasing caspases-3 and -8 proteins in the hippocampus, cerebral cortex, and cerebellum. The expression of the immediate-early gene BDNF was increased in response to TiO2 NPs, while that of Arc was reduced. Chitosan significantly attenuated the TiO2 NPs-induced neurotoxicity regarding AChE, serotonin, MDA, GSH, GPx, GST, IL-6, caspases-8, -9, and -3. Chitosan inhibited the expression of Arc and alleviated the effect of TiO2 NPs on BDNF expression. Collectively, TiO2 NPs induced neurotoxicity via their action on vital neuronal biomarkers that might in turn cause brain dysfunction. Despite the neuroprotection of chitosan, its inhibitory effect on Arc expression should be considered.

Biochemical and molecular investigation of oxidative stress associated with urolithiasis induced by increased dietary calcium or protein in chickens.

This study was carried out to evaluate the effects of induced urolithiasis by high dietary calcium (Ca) or protein levels on biochemical analyte levels, redox status, selected inflammatory cytokines and histopathology in chickens. A total of 90 one-day-old white Hy-Line chicks were fed basal control diets containing 20% crude protein (CP) and 1% Ca until they reached 44 days of age. After that, the birds were divided into three groups (30 birds per group). All management factors (light, temperature, ventilation, stock density and diet) were identical among the three groups throughout the study except for the dietary Ca and protein percentages. Group I was fed a control diet containing 20% CP and 1% Ca, group II was fed a high-Ca diet containing 5% Ca, and group III was fed a high-protein diet containing 25% CP. Our findings clearly demonstrated that dietary imbalance (caused by high-Ca or high-CP levels) per se in chickens was physiologically harmful, as it was accompanied by post-mortem lesions; biochemical, redox status and histopathological alterations; and upregulation of inflammatory cytokines (interleukin (IL)-1ß and IL-6). In particular, the birds fed the high-Ca diet clearly exhibited the most obvious alterations in most of the endpoints. In conclusion, this study constitutes the first extensive investigation of the effects of high-Ca or high-protein diets induced urolithiasis on growth performance, redox status, inflammatory cytokine levels and pathological characterization in chickens.

Antibacterial and antioxidant activity of clove oil against Streptococcus iniae infection in Nile tilapia (Oreochromis niloticus) and its effect on hepatic hepcidin expression.

This study was designed to evaluate the modulating effect dietary clove essential oil (CL) has on the antioxidant and immunological status of Nile tilapia following Streptococcus iniae (Si) infection. Fish were placed on either control or (1.5 and 3%) CL-supplemented diets for 4 weeks. After sampling, the remaining fish in the control group were divided into 2 groups: an unchallenged (negative control) and an Si-challenged positive control. On the other hand, the remaining fish in CL-supplemented groups were challenged with Si, and mortality was checked for two weeks before the final sampling. Serum immunological parameters, tissue antioxidants, and oxidative stress markers were determined. Moreover, hepatic hepcidin expression was also measured in different groups. The obtained results showed improvements in blood phagocytic, bactericidal, lysozyme, and respiratory burst activities in CL-supplemented fish before and after the Si challenge. Si-challenge caused a remarkable increase in tissue malondialdehyde (MDA) levels that was inhibited by CL supplementation. The activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in tissues were significantly elevated in a dose-dependent manner in CL-supplemented groups in both pre- and post-challenge experiments; renal SOD did not show any differences. Hepatic nitric oxide (NO) level was significantly decreased in CL-supplemented fish in a dose-dependent manner. In the post-challenge experiment, nitrosative stress was apparent in the liver and kidney; however, CL supplementation was sufficient to reverse it. Interestingly, a remarkable induction of the hepatic hepcidin expression was observed in all CL-supplemented groups in the pre-challenge experiment and Si-challenged fish, underscoring the role of CL as an antibacterial through inducing hepatic hepcidin expression to combat S. iniae infection. CL-supplementation was associated with lower mortality rates after Si-challenge, which was more pronounced in CL-3% supplemented fish. In conclusion, our results demonstrate that CL has a potent antioxidant role via increasing antioxidant enzymes' activities and antagonizing lipid peroxidation. Moreover, CL has an immune-stimulant effect by inducing the hepatic hepcidin expression and immunological markers in response to S. iniae infection.

The Effects of TiO2 Nanoparticles on Cisplatin Cytotoxicity in Cancer Cell Lines.

There have been many studies on improving the efficacy of cisplatin and on identifying safe compounds that can overcome multi-drug resistance (MDR) acquired by cancer cells. Our previous research showed that polyethylene glycol-modified titanium dioxide nanoparticles (TiO2 PEG NPs) affect cell membrane receptors, resulting in their aggregation, altered localization and downregulation. TiO2 PEG NPs may affect P-glycoprotein (P-gp), a membrane efflux channel involved in MDR. In this study, we investigated the effect of TiO2 PEG NPs on cisplatin cytotoxicity. We used HepG2 cells, which highly express P-gp and A431 cells, which show low expression of P-gp. The results showed that 10 µg/mL 100 nm TiO2 PEG NPs increased intracellular cisplatin levels and cytotoxicity in HepG2 cells but not in A431 cells. TiO2 PEG NPs treatment decreased the expression level of P-gp in HepG2 cells. Our findings indicate that TiO2 PEG NPs enhance cisplatin cytotoxicity by down regulating P-gp and that TiO2 PEG NPs are promising candidates for inhibiting P-gp and reversing drug resistance acquired by cancer cells.

EGF Conjugation Improves Safety and Uptake Efficacy of Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) have a strong potential for cancer therapeutic and bioimaging applications such as photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Our previous results have shown that TiO2 NPs have a low cellular uptake and can induce cell proliferation. This suggests that TiO2 NPs could increase the risk of tumor overgrowth while being used for PDD and PDT. To solve this problem, we constructed epidermal growth factor-ligated polyethylene glycol-coated TiO2 NPs (EGF-TiO2 PEG NPs). In this work, we studied the effect of EGF conjugation on the cellular uptake of TiO2 PEG NPs. Then, we investigated the effect of both non-conjugated and EGF-TiO2 PEG NPs on the A431 epidermal cancer cell line, proliferation and growth via the investigation of EGFR localization and expression. Our results indicated that TiO2 PEG NPs induced EGFRs aggregation on the A431 cells surface and induced cell proliferation. In addition, EGF-TiO2 PEG NPs induced the internalization of EGFRs inside of cells with increased cellular NPs uptake and decreased cellular proliferation compared to TiO2 PEG NPs-treated cells. These findings suggest that EGF conjugation can increase the efficacy of TiO2 PEG NPs for biomedical applications such as PDD and PDT with decreased risk of tumor overgrowth.

The effect of fucoidan or potassium permanganate on growth performance, intestinal pathology, and antioxidant status in Nile tilapia (Oreochromis niloticus).

Fucoidans are marine algal sulfated glycans that are widely used as dietary additives in aquaculture. These glycans are recognized as beneficial supplements for their antimicrobial, anti-inflammatory, anticancer, and antiviral properties. Potassium permanganate is another commonly used chemical that is used in aquaculture to treat infections in fish. Despite their widespread use, there are few data available regarding the potential sublethal toxicity associated with fucoidan and potassium permanganate treatments of fish. In this study, we investigated the effect of each compound on the growth, intestinal health, and antioxidant status of Nile tilapia (Oreochromis niloticus). Both compounds affected the growth of experimental fish compared with untreated fish. However, while growth parameters were positively associated with the dose of fucoidan administered, growth was negatively associated with the dose of potassium permanganate in Nile tilapia. Fucoidan treatment was observed to improve the intestinal health of fish based upon increases in intestinal villous area, intestinal villous length and width, and the intraepithelial lymphocyte number and decreases in the total intestinal bacterial count compared with untreated fish. Conversely, potassium permanganate induced intestinal epithelium proliferation and villous branching, a histopathological response typically observed with chemical irritants. Both fucoidan and potassium permanganate decreased levels of oxidative and nitrosative stress markers and enhanced the antioxidant status in multiple organs. Taken together, fucoidan dietary application improved the growth, intestinal health, and antioxidant status in Nile tilapia, supporting the use of this compound as a promising feed additive for aquaculture production. Conversely, potassium permanganate baths have negative effects on fish growth at higher doses and appeared to act as a gastrointestinal irritant in tilapia. This study improves knowledge regarding the biochemical and histological responses in Nile tilapia to two widely used aquaculture-related treatments.

The first molecular detection of Clostridium perfringens from pneumonic cases associated with foot and mouth disease in cattle and buffalo in Egypt.

Panting syndrome and respiratory infection have been recorded in complicated cases of foot and mouth disease (FMD) in cattle. However, investigations on the causative agents of respiratory disease in such cases are scarce. In this study, 30 animals (13 buffalo and 17 cattle) suffering from respiratory distress associated with signs of FMD were examined. Serum samples were collected and FMD infection was confirmed. Bacteriological examination of lungs from eight necropitized cases revealed the presence of C. perfringens. Multiplex polymerase chain reaction (mPCR) was performed on the positive samples followed by sequencing analysis. The alpha toxin gene (plc) of C. perfringens was identified in six cases. The present investigation highlights the role of clostridial infection as a complication of FMD in cattle and buffalo. This is the first report identifying the C. perfringens toxins from lung of animals with respiratory distress associated with FMD infection.

Molecular identification of Trichodina compacta Van As and Basson, 1989 (Ciliophora: Peritrichia) from cultured Oreochromis niloticus in Egypt and its impact on immune responses and tissue pathology.

Trichodinids are peritrichous ciliated protozoa that affect both wild and cultured fishes. Several Trichodina species have low host specificity and are morphologically distinct, facilitating their identification based primarily on the presence of adhesive discs and the number of attached denticles. A trichodinid species named Trichodina compacta was first reported by Van As and Basson (1989) (Protozoa: Ciliophora: Peritrichia). However, in trichodinid infestations, morphological characteristics are insufficient for identifying the infesting species. Therefore, molecular and phylogenetic analyses are considered to be promising and useful tools for identifying the infesting species. This study aimed to achieve the molecular identification of a trichodinid infestation in Nile tilapia and to construct the phylogenetic relationships between the identified species and other peritrichous parasites. Moreover, we also aimed to study the pathological and immunological impacts of trichodinids on fry tissue to improve our understanding of the immune responses of teleost fish to trichodinae parasitic infestations and develop a better control method. Here, we used molecular techniques to identify the isolated trichodina species as T. compacta and demonstrated that Trichodina infestation in Nile tilapia is associated with remarkable immunogenic and inflammatory responses (increased il-1ß expression and decreased il-8 and tgf-ß expression). These findings improve our understanding of the responses of teleost fish to trichodinid parasite infestation and will be helpful for the development of novel control strategies that reverse the inflammatory and immunogenic alterations that occur in infested fish.

Upregulation of heme oxygenase 1 (HO-1) attenuates kidney damage, oxidative stress and inflammatory reaction during renal ischemia/ reperfusion injury.

The current study investigated the effect of upregulation of heme oxygenase 1 (HO-1) by cobalt protoporphyrin (CoPP) on renal dysfunctions in renal ischemia/reperfusion (I/R) injury and its underlying mechanisms. 72 male Sprague Dawley rats were divided into 4 groups: sham group, ischemic group (left 45-min renal ischemia), CoPP-before group (as ischemic group with CoPP 20 mg/kg 30 min before ischemia) and CoPP-after group (as ischemic group with CoPP 20 mg/kg 20 min after ischemia). Serum creatinine, urea and TGF-ß1 and markers of redox state (MDA, SOD, GSH and CAT), nitric oxide (NO), TGF-ß1 and HO-1 in kidney tissues were measured. Serum creatinine and urea levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p < 0.05). Also, markers of redox state showed significant deteriorations in ischemic group which were improved significantly in CoPP-treated groups (p < 0.05). HO-1 expression in kidney tissues showed significant increase in ischemic group and showed more significant increase in CoPP-treated groups (p < 0.05). Moreover, serum and renal TGF-ß1 levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p ≶ 0.05). We concluded that up-regulation of HO-1 by CoPP treatment before and after renal I/R injury improved the kidney function and morphology and this might be due to impairment of oxidative stress and inflammatory cytokines in kidney tissues.

UGT1A1 morpholino antisense oligonucleotides produce mild unconjugated hyperbilirubinemia in cyclosporine A-induced cardiovascular disorders in BLC57 mice.

This study aimed to investigate the induction of mild unconjugated hyperbilirubinemia in hepatic UGT1A1 inhibition by Morpholinos antisense in CsA-treated BLC57 mice in comparison with the efficacy of chitosan (CH) as an anti-hypolipidemic natural product. Antisense morpholino oligonucleotides were injected intravenously into CsA-treated mice for 14 days thrice a week. Serum biochemical parameters, antioxidant status, and gene expression analysis of eNOS, PPAR-α, NF-kB, cFn, AT1-R, and ETA-R were determined in cardiac tissues with confirmation by histopathology. Inhibition of UGT1A1 significantly elevated serum unconjugated bilirubin within a physiological range. Furthermore, induced mild hyperbilirubinemia reduces hyperlipidemia, improves antioxidant status, and significantly increases the expression of the cardiac PPAR-α gene while decreasing, ETA-R, iNOS, NF-kB, cFn and AT1-R gene expression in CsA-treated mice. Importantly, mild unconjugated hyperbilirubinemia within physiological ranges may be used as a novel therapeutic strategy to lower hyperlipidemia, atherosclerosis, hypertension, and the CVD outcomes in CsA- treated transplant recipients.

Biochemical and molecular effects of a commercial diuretic with herbal extract on experimentally induced urolithiasis in chickens.

This study evaluated the diuretic, antioxidant, anti-inflammatory, and immunological effects of a commercial diuretic (CD) (composed of ammonium chloride, potassium citrate, sodium chloride, ascorbic acid, biotin, halfa bar extract, and hexamine) on chickens with induced urolithiasis. A total of 100 one-day-old white Hy-Line chicks were fed a basal diet containing 20% crude protein (CP) and 1% Ca until they reached 48 days of age. Then, the birds were divided into five groups (G1-G5). G1 was fed a basal diet and kept as a negative control, G2 was fed a high protein (HP) diet containing 25% crude protein, G3 was fed high calcium (HC) diet containing 5% Ca, G4 was fed HP diet supplemented with CD, and G5 was fed HC diet supplemented with CD. The CD was supplemented with drinking water (at a dose of 0.5 ml/ liter) for 1 week. The experiment was held for 78 days. Clinical signs, postmortem lesions, and mortality rates were observed. Biochemical analytes, redox status biomarkers, and expression of interleukin-6 (IL-6) and interferon-gamma (IFN-γ) were measured. Tissue samples were taken for histopathological examination. No signs of CD toxicity were observed during the toxicity test prior to the experiment. Compared to all groups, birds in G2 and G3 showed impaired renal function and alterations in biochemical, redox status, lipid peroxidation, post-mortem, and histopathological lesions along with upregulation of IL-6 and IFN-γ in the kidney and spleen. In conclusion, commercial diuretic supplementation for one week improves renal function, redox status, immune and anti-inflammatory responses in chickens with induced urolithiasis.

The Potential Protective Effect and Underlying Mechanisms of Physiological Unconjugated Hyperbilirubinemia Mediated by UGT1A1 Antisense Oligonucleotide Therapy in a Mouse Model of Cyclosporine A-Induced Chronic Kidney Disease.

Cyclosporine A (CSA) is an immunosuppressive drug that has improved transplant survival rates. However, its use is often limited because it is thought to be linked to the development of chronic kidney disease after kidney transplants. This study aimed to investigate the protective effects and underlying mechanisms of physiological unconjugated (UC) hyperbilirubinemia mediated by UGT1A1 antisense oligonucleotide in a mouse model of CsA-induced chronic kidney disease, and match these with that of chitosan (CH) as a natural chelator against kidney injury. In the current study, CsA-treated mice were given an intravenous injection of UGT1A1 antisense morpholino oligonucleotide (16 µg/kg) every third day for 14 days. In serum samples, bilirubin, creatinine, and urea were determined. Markers of oxidative stress, antioxidant activities, and mRNA expression of target genes PPAR-α, cFn, eNOS, NF-B, AT1-R, ETA-R, Kim-1, and NGAL were measured in the kidney tissues. Moreover, histopathological examinations were carried out on the kidney tissue. Physiological UC hyperbilirubinemia could be a promising protective strategy against CsA-induced kidney disease in transplant recipients. UGT1A1 antisense oligonucleotide-induced physiological UC hyperbilirubinemia serum significantly protected against CsA-induced kidney dysfunction. UCB acts as a signaling molecule that protects against kidney disease through different mechanisms, including antioxidant, anti-inflammatory, and hormonal action, by activating nuclear hormone receptors (PPAR-α). Moreover, it significantly downregulated mRNA expression of NF-kB, ETA-R, iNOS, AT1-R, cFn, Kim-1, and NGAL in the kidney tissue and alleviated CsA-induced kidney histological changes in CsA-treated mice.

Impact of chitosan administration on titanium dioxide nanoparticles induced testicular dysfunction.

The potential reproductive toxic effects of oral TiO2 NPs in adult male rats as well as the possible alleviation of chitosan administration was investigated. Animals were allocated to four groups; the first group received deionized water and was assigned as a control group. In the second group, rats received chitosan at a dose of 5 mg/kg BW/day. The third group was designed for administration of TiO2 NPs at a dose of 150 mg/kg BW/day (1/80 LD50). Rats in the fourth group received both TiO2 NPs and chitosan. After 14 days, TiO2 NPs induced testicular lipid peroxidation as well as oxidative stress. Nano-titanium significantly upregulated genes that encode apoptosis and inflammation in testicular tissue. Moreover, it induced histological alteration in the testicular structure with impairment in spermatogenesis via reduction of PCNA immune-staining. Chitosan administration significantly improved the activities of testicular GPx, SOD, and CAT enzymes. In addition, it significantly down-regulated the relative expressions of pro-apoptotic and pro-inflammatory testicular genes. Chitosan was able to improve the testicular architecture as well as spermatogenesis. The current study revealed the capability of chitosan to ameliorate nano-titanium induced testicular toxicity. Thus, attention should be given to the extensive consumption of nano-titanium particles.

Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton's Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury.

Objectives: The current work investigated the effect of Wharton jelly mesenchymal stem cells (WJ-MSCs) pretreated with all-trans-retinoic acid (ATRA) on renal ischemia in rats and the possible role of oxidative stress, apoptotic and Wnt/ß-Catenin signaling pathways, and inflammatory cytokines in their effects. Methods: The study included 90 male Sprague Dawley rats that were allocated to five groups (n = 18 rats): (I) Sham-operated group (right nephrectomy was performed); (II) Ischemia/reperfusion injury (IRI) group, a sham group with 45-min renal ischemia on the left kidney; (III) ATRA group, an ischemic group with an intravenous (i.v.) administration of ATRA 10 µM, 10 min post-surgery); (IV) WJ-MSCs group, an IRI group with an i.v. administration of 150 µL containing 7 × 106 WJ-MSCs, 10 min post-surgery; (V) WJ-MSCs + ATRA group, an IRI group with an i.v. administration of 150 µL of 7 × 106 WJ-MSCs pretreated with 10 µM ATRA. At the end of the experiments, serum creatinine, BUN micro-albuminuria (MAU), urinary protein, markers of redox state in the left kidney (MDA, CAT, SOD, and GSH), and the expression of Bax, IL-6, HIF-1α, Wnt7B, and ß-catenin genes at the level of mRNA as well as for immunohistochemistry for NFkB and ß-Catenin markers were analyzed. Results: The current study found that 45-min of renal ischemia resulted in significant impairment of kidney function (evidenced by the increase in serum creatinine, BUN, and urinary proteins) and deterioration of the kidney morphology, which was associated with a significant increase in redox state (evidenced by an increase in MDA and a decrease in GSH, SOD, and CAT), and a significant increase in inflammatory and apoptotic processes (evidenced by an increase in Bax and IL-6, NFkB, Wnt7B, ß-catenin and HIF-1α) in kidney tissues (p < 0.05). On the other hand, treatment with ATRA, WJ-MSCs, or a combination of both, caused significant improvement in kidney function and morphology, which was associated with significant attenuation of oxidative stress, apoptotic markers, and inflammatory cytokines (IL6 and NFkB) with the upregulation of HIF-1α and ß-catenin in kidney tissues (p < 0.05). Moreover, the renoprotective effect of WJ-MSCs pretreated with ATRA was more potent than WJ-MSCs alone. Conclusions: It is concluded that preconditioning of WJ-MSCs with ATRA may enhance their renoprotective effect. This effect could be due to the upregulation of the beta-catenin/Wnt pathway and attenuation of apoptosis, inflammation, and oxidative stress.

Fucoidan ameliorates acute and sub-chronic in vivo toxicity of the fungicide cholorothalonil in Oreochromis niloticus (Nile tilapia).

Fucoidans are sulfated glycans from marine algae that have both anti-cancer and anti-microbial properties. Chlorothalonil is a fungicide and insecticide commonly used in agriculture. Chlorothalonil is relatively toxic to fish and can potentially affect the aquaculture practices. In this study, we determined whether fucoidan administration would offer any protection from acute and subchronic toxicity of chlorothalonil on Nile tilapia. First, we tested the effect of chlorothalonil (20 to 140 µg/L, water-applied) on Nile tilapia in an acute exposure (six days). Survival analysis was performed, together with assessment of histopathology, oxidative stress (i.e., antioxidant status, hydrogen peroxide levels, malondialdehyde and nitric oxide levels) and immunohistochemistry to measure indicators of hepatic damage (i.e., caspase 3, p53, mini-chromosome maintenance proteins (MCM), and glutathione peroxidase). Chlorothalonil induced mild to severe histopathological alterations that were dose-dependent in various tissues of Nile tilapia. Chlorothalonil also induced oxidative stress as indicated by elevated biochemical markers. The highest recorded mortalities were associated with p53 expression. Additional feeding experiments were conducted with fucoidan (8 g/kg diet), following acute (40 µg/L for seven days) and sub-chronic (20 µg/L for six weeks) chlorothalonil application in Nile tilapia. Many of these same biochemical biomarkers of stress, oxidative damage response, and tissue pathology (evidence for hepatic neoplasm) were ameliorated by fucoidan, suggesting a protective effect of the compound. Agrochemicals are ubiquitous on a global scale, and the use of fucoidan as a feed additive may be beneficial for protecting aquatic animal health and aquaculture species from the impacts of chemical run-off.