Protective role of hesperidin in finasteride-induced testicular toxicity in adult male Wistar rats: Insights into oxidative stress, apoptosis, and ultrastructure of seminiferous tubules.

A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively. Testicular weight, sperm count and motility were determined. Testicular tissue homogenates were prepared to measure the level of malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH) and the gene expression of caspase-3 and B-cell lymphoma 2 (Bcl2). Testes were processed for light and electron microscopic evaluation. Johnsen score was calculated. Administration of finasteride resulted in significantly decreased testicular weights, sperm count and motility, Johnsen score, tissue levels of TAC and GSH together with significant increase in tissue MDA. Gene expression revealed significantly increased caspase-3 and decreased Bcl2. Furthermore, finasteride disrupted the seminiferous tubules, causing degenerative changes affecting Sertoli cells and spermatogenic cells. Co-administration of hesperidin with finasteride resulted in improvement in testicular weights, TAC, GSH, Bcl2, Johnsen score, sperm count and motility as well as preservation of the structure of the seminiferous tubules. To conclude, hesperidin was found to have a protective potential on finasteride-induced oxidative stress, apoptosis and testicular structural damage.

Regular use of ibuprofen reduces rat penile prostaglandins and induces cavernosal fibrosis.

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug that is noted for its favorable safety profile. It exerts its therapeutic effect through inhibition of prostaglandin (PG) production at inflammatory sites. However, the inhibition of PG synthesis at other sites is responsible for the occurrence of adverse events. Evidence regarding the effect of regular ibuprofen intake on penile PG homeostasis or penile histopathologic changes is lacking. The aim of this study was to examine the effect of regular administration of analgesic therapeutic doses of ibuprofen on penile PG E1 and F2α and penile microscopic changes of the treated rats. This study included four groups of adult male Wistar rats; a control group (I) injected intraperitoneally with saline (2 ml/kg/day) for 30 days and 3 ibuprofen-treated groups (IIa, IIb, and IIc) injected intraperitoneally with 6 mg/kg/day, 12 mg/kg/day, and 18 mg/kg/day ibuprofen, respectively, for 30 days, respectively. Mean levels of penile PGE1 and PGF2α in the control group were significantly higher than ibuprofen-treated groups IIa, IIb, and IIc. The percentage area of collagen around cavernous tissue was significantly higher in ibuprofen-treated groups IIa, IIb, and IIc than control rats. Our findings suggest that despite ibuprofen's safety profile, regular use of ibuprofen is associated with reduced penile PG and increased cavernosal fibrosis.

Adsorption Characteristics of Pristine and Magnetic Olive Stones Biochar with Respect to Clofazimine.

Olive stone biochars (OSBC), both pristine and following magnetization (MAG-OSBC), were utilized as eco-friendly and cost-effective sorbents for the antituberculosis, clofazimine (CLOF). Morphologies, textures, surface functionalities, and thermal stabilities of both adsorbents were explored using SEM, EDX, TEM, BET, FT-IR, Raman, XRD and TGA analyses. SEM analysis showed meso- and macroporous surfaces. BET data showed that the MAG-OSBC possesses a larger surface area (33.82 m2/g) and pore volume. Batch adsorption studies were conducted following the experimental scenario of Box-Behnken (BB) design. The adsorption efficiency of both adsorbents was evaluated in terms of the % removal (%R) and the sorption capacity (qe, mg/g). Dependent variables (%R and qe) were maximized as a function of four factors: pH, sorbent dose (AD), the concentration of CLOF ([CLOF]), and contact time (CT). A %R of 98.10% and 98.61% could be obtained using OSBC and MAG-OSBC, respectively. Equilibrium studies indicated that both Langmuir and Freundlich models were perfectly fit for adsorption of CLOF. Maximum adsorption capacity (qmax) of 174.03 mg/g was obtained using MAG-OSBC. Adsorption kinetics could be best illustrated using the pseudo-second-order (PSO) model. The adsorption-desorption studies showed that both adsorbents could be restored with the adsorption efficiency being conserved up to 92% after the sixth cycles.

Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction.

Chemotherapy induces an irreversible premature ovarian dysfunction (POD). Amniotic fluid mesenchymal stem cells (AFMSCs) can rescue fertility; however, the notion that stem cells can rejuvenate follicles is highly controversial due to the predetermined ovarian reserve. This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-Müllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFCs) were estimated from stained ovarian sections. Functional recovery was investigated through daily vaginal smears and mating trials. In vitro chemical transfection of the AFMSCs with selective miRNA-21 mimics/inhibitors followed by isolation of EVs for therapy was conducted in two additional groups. At the interval points studied, treatment with AFMSCs and EVs equally restored TFC, AMH levels, regular estrous cycles and fruitful conception, while it both diminished caspase 3 and PTEN levels. EVs carrying miRNA-21 mimics recapitulated the short-term effects. Placebo-treated POD or EVs carrying miRNA-21 inhibitors showed augmented ovarian follicular damage demonstrated the low AMH levels, TFC and high levels of PTEN and caspase 3. miRNA-21 allowed regeneration by modulating PTEN and caspase 3 apoptotic pathways. Our findings exemplify that EVs could serve as an innovative cell-free therapeutic tool functioning through their miRNA content and that miRNA-21 has a chief regenerative role through modulating PTEN and caspase 3 apoptotic pathways.

The effect of Tributyltin on thyroid follicular cells of adult male albino rats and the possible protective role of green tea: a toxicological, histological and biochemical study.

INTRODUCTION: Tributyltin is one of the important and wide-spread persistent organic contaminants that accumulate in the food chain. It is suspected to cause endocrine-disrupting effects in mammals, due in part to its possible transfer through marine food chains and to the consumption of contaminated seafood. AIM OF THE WORK: Was to study the possible toxic effect of Tributyltin on thyroid follicular cells of adult male albino rats and to evaluate the possible protective role of green tea. MATERIAL AND METHODS: Forty-five adult male albino rats were included and randomly divided into 3 equal groups: a control group (Group I); Group II: received tributyltin chloride (TBT) dissolved in corn oil orally in a dose of 5 mg/kg for 30 days. Group III: received tributyltin chloride in the same dose with concomitant oral administration of green tea extract for 30 days. At the end of the experiment, the animals were sacrificed and blood samples were subjected to hormonal assay for T3, T4 and TSH levels. Malondialdehyde and reduced glutathione were assessed. The thyroid tissue was processed for histological and ultrastructure examination. The colloid area of thyroid follicles was evaluated morphometrically and statistically analyzed. RESULTS: A significant decrease in T3 and T4 levels and serum reduced glutathione in the group II when compared with the other groups. Furthermore, a significant increase in serum Malondialdehyde and TSH levels was recorded in group II treated group by comparison to the other two groups. Histopathological and ultrastructural changes of thyroid gland follicles were detected in tributyltin treated rats; the follicular cells appeared swollen and vacuolated. Epithelial stratification was noticed in some foci with excessive vacuolation of the colloid. Dilated rough endoplasmic reticulum filled with flocculent material and increased number of lysosomes were also detected together with variation in shape and size of the nuclei. A marked improvement in the histological features of thyroid follicles was noticed in group III. CONCLUSION: Tributyltin induces oxidative stress in rats as well as anti-thyroid effect. The green tea extract is useful in combating tissue injury that is a result of tributyltin toxicity.

Histopathologic and Ultrastructural Changes in Seminiferous Tubules of Adult Male Albino Rats Following Daily Administration of Different Doses of Tadalafil.

OBJECTIVE: To investigate the effect of chronic daily administration of different doses of tadalafil on the structure of the seminiferous tubules and on spermatogenesis. MATERIALS AND METHODS: Sixty adult male Wistar rats were included; they were divided into four groups: a control group (group I) and groups II, III, and IV that received daily tadalfil in doses of 0.45, 0.9, and 1.8 mg/kg for 12 weeks (equivalent to human doses of 5, 10, and 20 mg daily), respectively. The epididymis was processed for evaluation of sperm parameters, serum testosterone was measured, Johnsen score for rats was calculated, and testicular histopathological and ultrastructural examinations were performed. RESULTS: Serum testosterone was significantly lower in group IV than in groups I and II. Moreover, posttreatment values in group IV were significantly lower than pretreatment values. A significant decline in sperm motility and morphology was detected in groups III and IV compared to groups I and II. Sperm count was significantly lower in group IV compared to the other groups. Johnsen score was significantly lower in groups III and IV compared to groups I and II and in group IV compared to group III. In addition, histopathological and ultrastructural degenerative changes in rat testes were detected; these changes were dose dependent and increased with increasing the dose of tadalafil. CONCLUSION: Chronic daily oral administration of tadalafil to male albino rats demonstrates a dose-dependent alteration to testicular histology and semen parameters. The influence of these changes on the actual fertility of these animals remains to be determined.

The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although--later--none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM-via fibrin vehicle--could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure.