Ameliorative effects of berberine and selenium against paracetamol-induced hepatic toxicity in rats.

Background: Paracetamol (PCM) overdosing induces hepatotoxicity, which can result in death if the dose is high enough and the patients are not given N-acetyl cysteine. Berberine (BBR) has a variety of biological proprieties including anti-inflammatory and antioxidant activities. Aim: Assessment of the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity in rats. Methods: This research involved 40 clinically healthy mature adult male albino rats, their weights ranged from 150 to 200 g and housed in standard conditions. Our study involved evaluating the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity via estimation of the liver function tests, determination of the antioxidant enzyme activities, lipid peroxidation markers, immune-modulatory effects, liver histopathological, and immunohistochemical studies. Results: Co-treatment of BBR (150 mg/kg BW) with selenium (5 mg/kg BW) showed significant improvement in the liver function parameters, the antioxidant enzyme activities, reduction in the nitric oxide (NO), lysozyme, malondialdehyde (MDA), TNF-α, and TGF-ß1 levels, and marked elevation in the IgM levels. Conclusion: Altogether, BBR, selenium, or both augment antioxidant activity and alleviate PCM-induced hepatic toxicity.

Prevalence and antibiogram of shigatoxinproducing E. coli in camel meat and offal.

Background: Camels are important animals in Egypt and other Arab countries on the basis of their economic value and ethnic culture. Escherichia coli is implicated in several gastrointestinal infections and outbreaks worldwide, especially in developing countries. It causes infections that might lead to death. Numerous biological activities, such as antioxidative, antibacterial, anti-diabetic, anti-mutagenic, anti-inflammatory, neuroprotective, and diuretic, are associated with coriander and coriander essential oils. Aim: This work targeted investigation of the prevalence, antibiogram, and occurrence of virulence genes of E. coli in camel meat liver and kidney. Besides, the anti-E. coli activity of coriander oil was further examined. Methods: Camel meat, liver, and kidneys were collected from local markets in Egypt. Isolation and identification of E. coli were performed. The antimicrobial susceptibility of the obtained E. coli isolates was screened using the disk diffusion assay. To detect the presence of virulence-associated genes (stx1, stx2, eaeA, and hylA gens), polymerase chain reaction was used. An experimental trial was done to investigate the anti-E. coli activity of coriander oil. Results: The obtained results revealed isolation of the following E. coli pathotypes: O17:H18, O128:H2, O119:H6, O103:H4, O145:H-, and O121:H7. The recovered E. coli isolates practiced multidrug resistance profiling with higher resistance toward Erythromycin, Nalidixic Acid, Clindamycin, and Ampicillin. However, the isolates were sensitive to Meropenem and cefoxitin. The recovered isolates had expressed different virulence attributes. Coriander oil of 2% could significantly reduce E. coli O128 count in camel meat by 65%. Conclusion: Therefore, strict hygienic measures are highly recommended during the processing of camel meat. The use of coriander oil during camel meat processing is highly recommended to reduce E. coli count.

Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations.

Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br-MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs-EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4 expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br-MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and expression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR-181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR, P62, TGF-ß, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression.

The Antiproliferative Activity of Adiantum pedatum Extract and/or Piceatannol in Phenylhydrazine-Induced Colon Cancer in Male Albino Rats: The miR-145 Expression of the PI-3K/Akt/p53 and Oct4/Sox2/Nanog Pathways.

Colon cancer is one of the most common types of cancer worldwide, and its incidence is increasing. Despite advances in medical science, the treatment of colon cancer still poses a significant challenge. This study aimed to investigate the potential protective effects of Adiantum pedatum (AP) extract and/or piceatannol on colon cancer induced via phenylhydrazine (PHZ) in terms of the antioxidant and apoptotic pathways and histopathologic changes in the colons of male albino rats. The rats were randomly divided into eight groups: control, AP extract, piceatannol (P), PHZ, PHZ and AP treatments, PHZ and P treatments, PHZ and both AP and P, and PHZ and prophylaxis with both AP and P. The results demonstrated that PHZ induced oxidative damage, apoptosis, and histopathological changes compared to the control group. However, the administration of AP or P or AP + P as therapy or prophylaxis significantly ameliorated these changes and upregulated the colonic mir-145 and mRNA expression of P53 and PDCD-4 while downregulating the colonic mRNA expression of PI3K, AKT, c-Myc, CK-20, SOX-2, OCT-4, and NanoG compared to the PHZ group. These findings suggest that the candidate drugs may exert their anti-cancer effects through multiple mechanisms, including antioxidant and apoptotic activities.

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction.

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150-180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity.

Concerns with Male Infertility Induced by Exposure to Titanium Nanoparticles and the Supporting Impact of Pelargonium graveolens Essential Oil: Morphometric Records in Male-Wistar Rats.

Background: Due to the increased use of titanium dioxide nanoparticles (TiO2 NPs), the risks of their reprotoxic effect arise. This study anticipated examining the potential protective effects of GEO (geranium essential oil) components screened via GC/MS analysis against the reprotoxic impacts of TiO2 NPs on male rats. Methods: Thirty-two adult male rats were randomly assigned to four groups: control, GEO (75 mg/kg bwt/orally/day/60 days), TiO2 NPs (100 ppm/rat/IP/day/60 days), and TiO2 NPs + GEO. After 60 days, hormonal assay, semen appraisal, lipid peroxidation, antioxidant enzymes, testis and prostate morphometry, and the steroidogenesis-related genes' mRNA expressions were assessed. Results: The TEM and DLS results demonstrated that synthesized TiO2 NPs are spherical with minimal aggregations polydispersed and varying in size from 50 to 100 nm. TiO2 NPs IP injection-induced sperm abnormalities decreased the percent of motile sperms in the sperm count, reduced sex hormone levels, altered the testicular oxidant/antioxidant status and mRNA expression of steroid-related genes, and induced architectural alterations in testicular, epididymal, and prostate gland tissues. GEO significantly rescued the TiO2 NPs-altered spermiogram, sex hormones, and antioxidant capacity, restored the tissue architectures, and enhanced steroidogenesis-related gene mRNA expression. Conclusions: These findings may significantly contribute to developing combinatorial treatments for infertility associated with various environmental and industrial xenobiotic exposures.

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies.

Acetylsalicylic acid (Aspirin) has been used for a long time as an antipyretic and analgesic. Nevertheless, aspirin use is associated with severe morbidity and death because of its detrimental impacts on several organs, including the liver, kidneys, and stomach. The current investigation sought to ascertain the influence of thymol in mitigating aspirin-mediated gastric and hepato-renal injury. This was done by 1) evaluating gastric juice volume and pH as well as pepsin and prostaglandin E2 level; 2) measuring serum biochemical parameters and proinflammatory cytokines; 3) determining tissue oxidant/antioxidant status, and 4) identifying a link with gastric, hepatic and renal histopathological changes. Forty-eight rats were segregated to six groups: normal control, Th100, Th200, ASA, Th100 + ASA, Th200 + ASA. Daily administration of aspirin (ASA, 150 mg/kg body weight) for 3 successive days induced a significant increase in gastric juice volume, pepsin activity, serum transaminases, alkaline phosphatase, urea, creatinine, tumor necrosis factor-α, myeloperoxidase, and tissue malondialdehyde levels. In contrast, a significant reduction in gastric pH, prostaglandin E2, tissue non-enzymatic antioxidant (glutathione), and enzymatic antioxidant (superoxide dismutase, glutathione peroxidase, and catalase) levels. These biochemical changes were accompanied by histological modifications that included changes to the normal gastric, hepatic, and renal architectures. Pretreatment and simultaneous oral treatment with thymol (100 or 200 mg/kg body weight) plus ASA significantly improved all biochemical and histological changes in a dose-dependent way. Thymol's antiinflammatory and antioxidative properties may contribute to its protective action. As a result, thymol may represent a promising medication for preventing aspirin-induced gastric, liver, and renal damage.

Risk factors of penile resurfacing in re-operative hypospadias repair: A retrospective analytical study.

INTRODUCTION: In re-operative hypospadias repair, scarred urethral plate, and deficient unhealthy penile skin are usually problematic. Difficulties are not only in urethroplasty but also in penile skin coverage. Penile skin coverage after urethroplasty with good viable skin decreases the complication rate and increases the satisfaction with repair. Studies reporting variables that increase the risks of the need for penile resurfacing in re-operative hypospadias are lacking. OBJECTIVES: To determine the risk factors of the need for penile resurfacing techniques (PRSTs) in re-operative hypospadias. STUDY DESIGN: A retrospective analysis of the redo hypospadias cases operated in-between January 2010 and December 2020 was done. Surgical data of the previous repairs, the indications for intervention, and the penile shaft coverage techniques at the time of the last repair were collected and analyzed. Patients' records were reviewed and categorized into two main groups. Group one include patients with simple skin closure, and group two include patients in whom penile resurfacing was done. Univariate analysis and Stepwise logistic regression measured the risk factors of the need for penile resurfacing techniques. RESULTS: Out of 223 re-operative hypospadias, simple skin closure was done in 105 (group 1). Penile skin resurfacing (Byars flaps, Heineke-Mikulicz technique, and Z-Plasty) was in 55 (group 2a). In 63 patients (group 2b), scrotal flaps and skin grafts (split and full thickness) were the PRSTs. Patients ages, proximal hypospadias, number of prior surgery, one-stage repair, penile skin use in repair especially flap techniques, more than one complication in the same case, and unsatisfactory skin appearance increased the risk for PRSTs. Each previous repair increases the odds ratio of penile and non-penile resurfacing 1.9 and 3.2 folds respectively. One-stage repair increases odds of PRSTs 4 folds. DISCUSSION: We analyzed the risk factors of the need for penile resurfacing techniques in the re-operative hypospadias cases. Step-wise logistic regression showed that the number of previous repairs and one-stage repair are the independent risk factors of penile resurfacing. Also, it showed that the number of prior surgeries is the only independent risk factor for non-penile skin resurfacing. CONCLUSION: Number of previous repair is the independent risk factors of penile resurfacing and non-penile skin use in resurfacing. Previous repair in one-stage is an independent risk factor of the need for penile resurfacing.

Extensive Drug-Resistant Salmonella enterica Isolated From Poultry and Humans: Prevalence and Molecular Determinants Behind the Co-resistance to Ciprofloxacin and Tigecycline.

The emergence of extensive drug-resistant (XDR) Salmonella in livestock animals especially in poultry represents a serious public health and therapeutic challenge. Despite the wealth of information available on Salmonella resistance to various antimicrobials, there have been limited data on the genetic determinants of XDR Salmonella exhibiting co-resistance to ciprofloxacin (CIP) and tigecycline (TIG). This study aimed to determine the prevalence and serotype diversity of XDR Salmonella in poultry flocks and contact workers and to elucidate the genetic determinants involved in the co-resistance to CIP and TIG. Herein, 115 Salmonella enterica isolates of 35 serotypes were identified from sampled poultry (100/1210, 8.26%) and humans (15/375, 4.00%), with the most frequent serotype being Salmonella Typhimurium (26.96%). Twenty-nine (25.22%) Salmonella enterica isolates exhibited XDR patterns; 25 out of them (86.21%) showed CIP/TIG co-resistance. Exposure of CIP- and TIG-resistant isolates to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor resulted in an obvious reduction in their minimum inhibitory concentrations (MICs) values and restored the susceptibility to CIP and TIG in 17.24% (5/29) and 92% (23/25) of the isolates, respectively. Molecular analysis revealed that 89.66% of the isolates contained two to six plasmid-mediated quinolone resistance genes with the predominance of qepA gene (89.66%). Mutations in the gyrA gene were detected at codon S83 (34.62%) or D87 (30.77%) or both (34.62%) in 89.66% of XDR Salmonella. The tet(A) and tet(X4) genes were detected in 100% and 3.45% of the XDR isolates, respectively. Twelve TIG-resistant XDR Salmonella had point mutations at codons 120, 121, and 181 in the tet(A) interdomain loop region. All CIP and TIG co-resistant XDR Salmonella overexpressed ramA gene; 17 (68%) out of them harbored 4-bp deletion in the ramR binding region (T-288/A-285). However, four CIP/TIG co-resistant isolates overexpressed the oqxB gene. In conclusion, the emergence of XDR S. enterica exhibiting CIP/TIG co-resistance in poultry and humans with no previous exposure to TIG warrants an urgent need to reduce the unnecessary antimicrobial use in poultry farms in Egypt.