Methotrexate (MTX) is mainly used as antimetabolite agents in cancer therapy. It causes serious side effects such as nephrotoxicity, hepatotoxicity, and anemia. Nigella sativa (NS) is a medicinal herb that has protective effects against the MTX-related side effects. The study aimed to determine the optimal concentration of the combination of NS-MTX mixture to improve the antitumor effects of MTX and reduce its related adverse effects. In this study, in vitro evaluation of anti-tumor and anti-angiogenic activities ofNS,MTX, or their mixture in different concentrations using liver hepatocellular carcinoma and endothelial cells were performed. The protective effects of NS on normal hepatic and kidney cells against the risks of MTX treatment was also tested in vitro. Moreover, for in vivo evaluation, male Wistar rats were treated with MTX or a combination of MTX and NS. Hematological and serological, biochemical, functional, and histopathological studies were performed. The results showed that the low concentration of NS enhanced the anti-tumor and anti-angiogenic effects ofMTX.Moreover, it had protective effects on normal hepatic and kidney cells against toxicity induced by MTX treatments. The in vivo results showed significant improvements in the blood condition and liver functional parameters in MTX-intoxicated rats after treating with NS. NS reduced the oxidative stress indices in both kidney and liver tissues. The histopathological examinations showed that NS reduced degenerative changes and necrosis in both kidney and liver. These results suggested that NS in low concentration could improve the efficacy and the safety of MTX treatment.

The current work was undertaken to test the genotoxic potential of chlorpyrifos (CPF), dimethoate, and lambda cyhalothrin (LCT) insecticides in rat brain and liver using the single cell gel electrophoresis (comet assay). Three groups of adult male Sprague-Dawley rats were exposed orally to one third LD50of CPF, dimethoate, or LCT for 24 and 48 h while the control group received corn oil. Serum samples were collected for estimation of malondialdehyde (MDA) and glutathione peroxidase (GPx); the brain and liver samples were used for comet assay and for histopathological examination. Results showed that signs of neurotoxicity appeared clinically as backward stretching of hind limb and splayed gait in dimethoate and LCT groups, respectively. CPF, LCT, and dimethoate induced oxidative stress indicated by increased MDA and decreased GPx levels. CPF and LCT caused severe DNA damage in the brain and liver at 24 and 48 h indicated by increased percentage of DNA in tail, tail length, tail moment, and olive tail moment. Dimethoate induced mild DNA damage in the brain and liver at 48 h. Histopathological changes were observed in the cerebrum, cerebellum, and liver of exposed rats. The results concluded that CPF, LCT, and dimethoate insecticides induced oxidative stress and DNA damage associated with histological changes in the brain and liver of exposed rats.

The current study was undertaken to explain the cytogenetic and genotoxic effects of penconazole (PEN) fungicide and chlorpyrifos (CPF) insecticide in male rats. Rats (n=10/group) were treated with 500 mg/kg body weight PEN orally for 24 h, 48 h and 100 mg/kg body weight for 30 days and the control animals were administered distilled water only. Chlorpyrifos exposed groups received 39 mg/kg body weight for 24 h and 48 h and 8 mg/kg body weight for 30 days by oral gavage and the control group was received corn oil. Blood samples were collected for complete blood count. Bone marrow was flushed from the femur bones for chromosomal aberration (CA) and comet assay. Spleen samples were preserved in 10% formalin for histopathological examination. The level of DNA damage was measured using DNA damage index. The results showed that PEN and CPF caused significant hematological changes, significant increase in DNA damage index and increased the number of nuclei with I, II, III and IV degrees of damage. Different types of CA were recorded in PEN and CPF exposed groups including chromosomal break, deletion, attenuation, chromosome ring, gap and fragments. In addition, numerical aberration as polyploidy appeared in CPF exposed groups only. PEN and CPF caused histopathological changes in spleen in the form of apoptosis, congestion, thrombosis and hemosiderosis. In conclusion, PEN and CPF induced genotoxic and cytogenetic effects in bone marrow. DNA damage index and the percentage of CA were higher in CPF than PEN groups.

Abstract Keywords: Abdominal Adhesion; Coeliotomy; Aetiology; Surgery; Physiology; Histopathology; Rabbit Background: Peritoneal adhesions are serious postoperative concern of coeliotomy and other abdominal surgeries, and can result in chronic pain, infertility, or potentially fatal bowel obstruction. Therapeutic and preventive measures have reduced adhesion formation to variable degrees in preclinical studies and clinical trials; however, there is incomprehensible understanding why the incidence of adhesion remains prominent in rabbits and human, at general surgery and gynaecological patients, respectively. Objectives: We adopted a prospective, non-controlled, randomised clinical trial to study potential risk factors that may predispose to coeliotomy operations, and to discover and analyze whether surgical, physiological and histopathological aetiology plays an influential role in abdominal adhesion formation. Methods: Thirty female adult rabbits (n = 30) with bodyweight of 1055 - 2910 gm (1965 ± 97.4 gm) and age of 63 - 132 days (111 ± 5.5 days) were subject to this study. The rabbits were randomly categorized into 2 groups; surgical intervention (n = 28) and control group (n = 2). Animals of the surgical intervention group underwent a median coeliotomy, whereas control group had no intervention. On the 10th and 17th postoperative day after surgery, gross observation and histopathological examination were carried out for each wound outcome. Results: Eighteen (n = 18/28) incisions (64.3%) developed a healthy fibrous scar without any serious complication. Of such incisions, 9 cases (32.1%) were each observed at days 10 and 17. Eight (n = 8/28) cases of abdominal adhesion (28.6%) were seen among the interventional group, of such; 4 cases (14.3%) were presented with adhesions at both days 10 and 17. Conclusions: Abdominal adhesions may elicit by a synergistic interaction of surgical, physiological and histopathological aetiologies.Genetics, breeds, biomaterials, and technical considerations are questionable of their effects, and arise of an utmost interest to speculate as risk factors.

Abstract Keywords: Abdominal Adhesion; Coeliotomy; Aetiology; Surgery; Physiology; Histopathology; Rabbit Background: Peritoneal adhesions are serious postoperative concern of coeliotomy and other abdominal surgeries, and can result in chronic pain, infertility, or potentially fatal bowel obstruction. Therapeutic and preventive measures have reduced adhesion formation to variable degrees in preclinical studies and clinical trials; however, there is incomprehensible understanding why the incidence of adhesion remains prominent in rabbits and human, at general surgery and gynaecological patients, respectively. Objectives: We adopted a prospective, non-controlled, randomised clinical trial to study potential risk factors that may predispose to coeliotomy operations, and to discover and analyze whether surgical, physiological and histopathological aetiology plays an influential role in abdominal adhesion formation. Methods: Thirty female adult rabbits (n = 30) with bodyweight of 1055 - 2910 gm (1965 ± 97.4 gm) and age of 63 - 132 days (111 ± 5.5 days) were subject to this study. The rabbits were randomly categorized into 2 groups; surgical intervention (n = 28) and control group (n = 2). Animals of the surgical intervention group underwent a median coeliotomy, whereas control group had no intervention. On the 10th and 17th postoperative day after surgery, gross observation and histopathological examination were carried out for each wound outcome. Results: Eighteen (n = 18/28) incisions (64.3%) developed a healthy fibrous scar without any serious complication. Of such incisions, 9 cases (32.1%) were each observed at days 10 and 17. Eight (n = 8/28) cases of abdominal adhesion (28.6%) were seen among the interventional group, of such; 4 cases (14.3%) were presented with adhesions at both days 10 and 17. Conclusions: Abdominal adhesions may elicit by a synergistic interaction of surgical, physiological and histopathological aetiologies.Genetics, breeds, biomaterials, and technical considerations are questionable of their effects, and arise of an utmost interest to speculate as risk factors.

Abstract Keywords: Abdominal Adhesion; Coeliotomy; Aetiology; Surgery; Physiology; Histopathology; Rabbit Background: Peritoneal adhesions are serious postoperative concern of coeliotomy and other abdominal surgeries, and can result in chronic pain, infertility, or potentially fatal bowel obstruction. Therapeutic and preventive measures have reduced adhesion formation to variable degrees in preclinical studies and clinical trials; however, there is incomprehensible understanding why the incidence of adhesion remains prominent in rabbits and human, at general surgery and gynaecological patients, respectively. Objectives: We adopted a prospective, non-controlled, randomised clinical trial to study potential risk factors that may predispose to coeliotomy operations, and to discover and analyze whether surgical, physiological and histopathological aetiology plays an influential role in abdominal adhesion formation. Methods: Thirty female adult rabbits (n = 30) with bodyweight of 1055 - 2910 gm (1965 ± 97.4 gm) and age of 63 - 132 days (111 ± 5.5 days) were subject to this study. The rabbits were randomly categorized into 2 groups; surgical intervention (n = 28) and control group (n = 2). Animals of the surgical intervention group underwent a median coeliotomy, whereas control group had no intervention. On the 10th and 17th postoperative day after surgery, gross observation and histopathological examination were carried out for each wound outcome. Results: Eighteen (n = 18/28) incisions (64.3%) developed a healthy fibrous scar without any serious complication. Of such incisions, 9 cases (32.1%) were each observed at days 10 and 17. Eight (n = 8/28) cases of abdominal adhesion (28.6%) were seen among the interventional group, of such; 4 cases (14.3%) were presented with adhesions at both days 10 and 17. Conclusions: Abdominal adhesions may elicit by a synergistic interaction of surgical, physiological and histopathological aetiologies.Genetics, breeds, biomaterials, and technical considerations are questionable of their effects, and arise of an utmost interest to speculate as risk factors.

The changes in the ovarian stroma of the fish during their spawning season become it an excellent biological model for studies on cellular and vascular elements due to the intense tissue remodeling in fish occur naturally throughout this critical period. The present study aims to investigate the cellular and vascular components of the ovarian stroma of Redbelly tilapia during the spawning season by conventional, immunohistochemical stains as well as to detect the ultrastructural characteristics for each stromal component. The histological examinations revealed a series of blood vessels with special structures, include throttle artery, glomus, spirally oriented arterioles, modified arteries, and veins as well as arteriovenous anastomosis. Various types of cells were detected in the stroma include; telocytes, rodlet cells, mast cells, eosinophils, neutrophils, lymphocytes, fibroblasts, macrophages, melanocytes, adipocytes, dendritic cells, and endocrine (steroidogenic, interstitial) cells. Moreover, these stromal cells showed a broad range of staining affinity against c-kit, desmin, and s100-protein. Bundles of nerve fibers were detected between the follicles. This study exposed various cellular and vascular components with distinct functions in the ovary of Redbelly tilapia during the spawning season.

The role of retinoid-related orphan receptor, one of the transcription factors reported in testis, in testicular function is unclear, so this study was performed to evaluate the qualitative and quantitative changes in the testicular structure of RORα-deficient mice using light-, electron-microscopy, and immunohistochemistry. Among the most striking alterations observed in the testis of the mutant mice were hypospermatogenesis, marked reduction in volume proportions of interstitial tissues and number of Leydig cells, significant decrease in the diameter of seminiferous tubules and height of their epithelium, vacuolation in the epithelium of the seminiferous tubules with occurrence of mast cells, appearance of delay spermiation signs, and changes in sperm morphology. Moreover, the testis of mutant mice showed symplasts, in addition to appearance of multinucleated giant bromophenol-positive cells. ATPase activity was limited to spermatogonia and some primary spermatocytes, with higher alkaline phosphatase expression. Stronger vimentin reaction was immunolocalized to spermatogonia, spermatids, Leydig cells, and Sertoli cells. The expression of CD117 (C-kit, stem cell growth factor receptor) was limited to spermatogonia, primary spermatocytes, and Leydig cells. Seminiferous tubules showed overexpression of vascular endothelial growth factor (VEGF). Transmission electron microscopy examination of the mutant mice revealed abnormal Sertoli cells, hypertrophied spermatogonia, spermatocytes with degenerated mitochondria, and incompletely developed sperms. In conclusion, RORα is one of the essential proteins that regulate testicular structure.

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