Protective role of resveratrol on testicular germ cells in mice with testicular toxicity

WOS: 000416270600010Objective: The aim of the present study was to investigate the possible beneficial effects of resveratrol in mice subjected to vinyl cyclohexene dieposide (VCD) -induced testicular toxicity. Material and methods: A total of thirty-six Swiss albino male mice aged 28-days were used in the present study. The study was composed of two stages where mice which received or did not receive VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into control and resveratrol-treated groups in the first stage and into groups of VCD- and VCD+resveratrol-treated groups in the second stage. At the end of the experiments, relative testicular weight (TW/BW) and dry/wet weight of testis (TDW/TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E) staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum testosterone, LH and FSH levels were measured by a commercially available ELISA kit. Results: Resveratrol caused a dose-dependent increase in TW/BW and decrease in TDW/TWW (p<0.05). Resveratrol at a dose of 20 mg/kg resulted in an improvement in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height of testicular seminipherous tubuli significantly after VCD exposure (p<0.001). Conclusion: Results of the present study suggest that resveratrol can be used as a protective and/or therapeutic agent particularly for cases with male infertility caused by testicular toxicity

The therapeutic potential of amifostine on cyclophosphamide-induced testicular dysfunction in rats: An experimental study

Background: Cyclophosphamide (CP) is a well-known alkylating anticancer agent used in the treatment of various malignant and non-malignant tumors. CP may also cause a variety of adverse effects, including reproductive toxicity. Amifostine is known as a cytoprotective drug having antioxidant properties. Objective: To evaluate the possible beneficial effects of amifostine on testicular toxicity induced by CP in rats. Materials and Methods: A total of 35 Sprague-Dawley rats were used in this experimental study. The CP group animals received a single dose of 200 mg/kg CP on Day 8 by intraperitoneal injection and were left untreated for the following seven days. The two remaining groups of animals were treated with 200 mg/kg/day amifostine (AMF 200) and 400 mg/kg/day amifostine (AMF 400) for seven days prior to and following a single intraperitoneal injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were measured in serum using commercial ELISA kits. The epidydimal sperm count was determined. Results: The tubular epithelial height in the testis was significantly higher in the AMF400 group compared to other groups (p &lt; 0.001). Animals in the AMF400 group showed minimal debris in the tubules, no Sertoli cell damage, and the Johnsen scores were slightly higher in the AMF400 group. The epididymal sperm count was significantly lower in the CP-administered animals compared to the control animals and was significantly higher in the AMF200 and AMF400 groups compared to the CP group (p = 0.006, and p = 0.019 respectively). Conclusion: Amifostine, at a dose of 400 mg/kg, may have a protective effect on testicular damage induced by CP in rats

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice

Comparison of stroke cases with other neurological diseases on the basis of haemogram parameters

Aims This study aimed to examine the haemogram parameters, including the neutrophil/lymphocyte ratio (NLR), which is fast, easy and practical to determine, in stroke patients who present with more physiological stress and inflammation and compare them with patients presenting other neurological diseases. Methods The demographic, laboratory and imaging features of all patients who were admitted to the neurology clinic within a three-year period and met the study criteria were retrospectively analysed. A haemogram from peripheral venous blood samples was taken at the time of admission, and its parameters was calculated. Results A total of 3152 patients, 1604 of whom were women (50.9%), with a mean age of 66.1 +/- 14 (18-100) years who were hospitalised in the neurology clinic from 1 January 2015 to 1 January 2018, comprised the study's sample. Mean age, mean leukocyte-neutrophil count and NLR were significantly higher in stroke patients than in those without stroke (P < .001, P P < .001, respectively), but mean red blood cell, platelet and lymphocyte counts, and haemoglobin and haematocrit values were found to be significantly lower (P < .001, P < .001, P < .001, P P < .001, respectively). When the haemogram parameters were compared according to stroke type, red blood cell, haemoglobin, haematocrit and NLR values in patients with haemorrhagic stroke (P = .019, P = .002, P = .002 and P = .001, respectively) and platelet and lymphocyte values in ischaemic stroke patients were found to be significantly higher (P = .002 and P < .001, respectively). Conclusion In this study, significant data obtained by comparing the haemogram parameters of those with stroke and other neurological diseases are presented. All neurological diseases, especially acute stroke and its types, should be examined in future prospective, randomised and controlled studies with all haemogram parameters, especially the NLR. However, it should be noted that haematological parameters are more useful for group studies rather than determining the diagnosis of an individual patient

Bilateral Paraneoplastic Vitritis: Report of a Case

This report describes the case of a patient who presented with bilateral vitritis that led to a diagnosis of small-cell lung cancer (SCLC). A 70-year-old man was examined due to bilateral gradual visual deterioration. Symmetrical vitritis was observed in both eyes with no evidence of other fundus pathology. The opthalmological diagnosis was bilateral paraneoplastic vitritis. The patient was an active smoker and had a short history of weight loss. A systemic evaluation resulted in a diagnosis of SCLC. The appropriate cancer treatment was provided, as well as a short-term oral steroid. The vitritis responded well to steroid treatment. Ocular manifestations can be an early sign of malignancy, and ophthalmologists should be aware of this possibility

Estrogen-like Activity of Quercetin in Female Rats

WOS: 000383612800002Objective: Quercetin is a phytoestrogen that exerts both in vitro agonistic and antagonistic activities on estrogen receptors. The present study evaluated the in vivo estrogen-like activity of quercetin on the reproductive organs of female rats. For this purpose, a partial estrogen agonist tamoxifen (TMX) and an estrogen antagonist fulvestrant (FLV) were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. 4-Vinylcyclohexene dioxide (VCD) was used to induce primary ovarian failure in rats. Materials and Methods: In experiment 1, immature female rats (21-22 days old) were treated with a vehicle (control), quercetin (10, 30, and 90 mg/kg), 10 mg/kg of quercetin (Q10)+TMX, Q10+FLV, 17 beta-estradiol (17 beta E), 17 beta E+TMX, or 17 beta E+FLV. In experiment 2, prepubertal female rats (28-29 days old) were treated with a vehicle (dimethyl sulfoxide), VCD-alone, VCD+Q10, or VCD+17 beta E. A uterotrophic assay and histological analysis of uteri were performed. The partial estrogen agonist TMX and the estrogen antagonist FLV were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. VCD was used to induce primary ovarian failure in rats. Results: In immature female rats, the uterine weight was significantly higher in animals treated with Q10 compared to those treated with the vehicle. Although TMX did not result in a significant change, FLV significantly decreased the uterine weight in Q10-treated rats. In prepubertal female rats, the uterine weight significantly decreased in VCD +/- Q10- or 17 beta E-treated animals compared that in VCD-treated animals. Although the endometrial thickness was unchanged in Q10-treated animals, it was significantly decreased in the Q10+FLV-treated animals. VCD significantly decreased the endometrial thickness, which was prevented by Q10. Conclusion: Quercetin may have a dose-dependent and biphasic effect on the uterus by modulating estrogen receptors