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1.
Exp Mol Pathol ; 137: 104901, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38749364

ABSTRACT

AIMS: The aim of this study was to investigate the potential antioxidant, anti-inflammatory, and sperm function-preserving properties of sodium acetate (ACE), a histone deacetylase (HDAC) inhibitor, in a rat model of testicular torsion/detorsion (T/D). MAIN METHODS: Littermate Wistar rats of identical weight were subjected to sham surgery or testicular T/D by rotating the left testis at 720° around its axis along the spermatic cord clockwise and fixing it in this position for two and a half hours. 1 h before detorsion, T/D + ACE-treated rats were treated with ACE (200 mg/kg/day, per os) while T/D rats were vehicle-treated by administering 0.5 mL of distilled water. After 72 h, animals were euthanized, and the left testes were harvested for bio-molecular and histological analysis. KEY FINDINGS: Acetate administration attenuated T/D-induced rises in serum and testicular HDAC and testicular xanthine oxidase, uric acid, MDA, GSSG, MPO, TNF-α, IL-1ß, IL-6, NFkB, HIF-1α, and VCAM-1. In addition, acetate treatment alleviated T/D-induced decline in sperm quality (count, motility, viability, and normal morphology) and testicular 3ß-HSD, 17ß-HSD, testosterone, GSH, GSH/GSSG, SOD, catalase, GPx, GST, Nrf2, and HO-1. Furthermore, acetate prevented T/D-distorted testicular histoarchitecture and spermatogenic germ cell loss. SIGNIFICANCE: Sodium acetate during the post-ischaemic phase of testicular T/D may be beneficial in preventing I/R injury and maintaining fertility.

2.
Redox Rep ; 28(1): 2225675, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37345699

ABSTRACT

AIM: The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function. METHODS: Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days. RESULTS: Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities. CONCLUSION: This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.


Subject(s)
Erectile Dysfunction , Testosterone , Male , Rats , Animals , Humans , Zinc/therapeutic use , Erectile Dysfunction/chemically induced , Erectile Dysfunction/drug therapy , Acetylcholinesterase , NF-E2-Related Factor 2 , Rats, Wistar , Uric Acid
3.
Appl Biochem Biotechnol ; 195(8): 4936-4964, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37115384

ABSTRACT

Erectile dysfunction (ED) is a major challenge for men. The drugs for its treatment are associated with side effects. Hence, in phytomedicinal research, where Anonna senegalensis (A. senegalensis) is a candidate with abundant phytochemicals possessing various pharmacological properties, but the sex-enhancing phytochemical is elusive in the literature. This study aimed to understand the molecular interaction of its potent molecule mediating male sexual enhancement. A library of 69 compounds from A. senegalensis was docked against the ED-targeted proteins. Sildenafil citrate was used as the reference standard. Thereafter, the lead compound was screened for drug-likeness by applying the Lipinski rule of 5 (RO5), pharmacokinetic properties, and bioactivity using SwissADME and Molinspiration web servers, respectively. The results show catechin as the lead phytochemical compound with a stronger binding affinity for most of the proteins of ED. Also, catechin demonstrates good compliance with the RO5, great pharmacokinetic profiles, and could be said to be a polypharmacological molecule with good bioactivity scores. The research findings unravel the potential of catechin (a phytochemical belonging to the flavonoids class) from A. senegalensis leaf as a potential male sexual enhancement molecule via its high binding affinity for most erectile dysfunction-targeted proteins. They may require further toxicity and therapeutic evaluations in vivo.


Subject(s)
Catechin , Erectile Dysfunction , Humans , Male , Erectile Dysfunction/drug therapy , Catechin/therapeutic use , Piperazines/adverse effects , Purines , Sildenafil Citrate/pharmacology , Sildenafil Citrate/therapeutic use , Treatment Outcome
4.
Life Sci ; 266: 118913, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33333050

ABSTRACT

AIM: Cyclophosphamide (CYP) chemotherapy induces bladder toxicity and hemorrhagic cystitis in cancer patients constituting a current clinical concern. Oxidative inflammatory cascades have been implicated as the mechanism contributing to CYP bladder urotoxicity. We thus assayed to explore whether zinc (Zn) supplementation could mitigate CYP-induced urotoxicity and evaluate the possible underlying mechanism in rats. MAIN METHOD: Rats were orally administered Zn (100 mg/kg b.w./day) for 10 days against urotoxicity induced by single injection of CYP (150 mg/kg b.w., ip) on day 7. KEY FINDINGS: CYP significantly depressed bladder activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels, whereas malondialdehyde level was increased prominently. In addition, CYP induced marked increases in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by histological alterations. CYP prominently increased bladder inducible nitric oxide synthase (iNOS) activity, nuclear factor-kappa B (NF-ĸB) and expression of caspase-3 protein. Zinc supplementation considerably abrogated the bladder urotoxicity by restoring redox balance, proinflammatory and apoptotic cascades and alleviated histopathological changes. SIGNIFICANCE: This is the first to reveal zinc potential to prevent CYP-induced urotoxic hemorrhagic cystitis via restoring redox balance and enhancing anti-inflammatory and antiapoptotic mechanisms in rat bladder.


Subject(s)
Cyclophosphamide/toxicity , Cystitis/prevention & control , Dietary Supplements , Gene Expression Regulation/drug effects , Hemorrhage/prevention & control , Zinc/pharmacology , Animals , Antineoplastic Agents, Alkylating/toxicity , Caspase 3/chemistry , Caspase 3/genetics , Caspase 3/metabolism , Cystitis/chemically induced , Cystitis/metabolism , Cystitis/pathology , Hemorrhage/chemically induced , Hemorrhage/metabolism , Hemorrhage/pathology , Male , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar
5.
J Food Biochem ; 44(1): e13100, 2020 01.
Article in English | MEDLINE | ID: mdl-31721240

ABSTRACT

Gentamicin is an effective antibiotic against severe infections; however, its major side effect is oxidative nephrotoxicity. We explored whether virgin coconut oil (VCO) could mitigate gentamicin-induced nephrotoxicity. Rats were fed with VCO-supplemented diet for 16 days against renal toxicity induced by gentamicin (100 mg/kg bw, ip) from Day 11 to 16. Gentamicin caused marked elevated serum urea, uric acid, and creatinine levels, followed by considerable depletion in renal antioxidant enzymes, glutathione (GSH), while the malondialdehyde (MDA) level increased significantly. It significantly increased renal cytokines and nitric oxide (NO) levels, confirmed by renal histopathology. The expression of inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-ĸB), and caspase-3 was prominently increased. VCO-supplemented diet significantly modulated the levels of biochemical indices, downregulated the expression of NO, iNOS, NF-ĸB, caspase-3, cytokines, and alleviated histopathological lesions. VCO protects against gentamicin-induced nephrotoxicity; thus, it could be a promising dietary supplement for patients undergoing gentamicin treatment. PRACTICAL APPLICATIONS: Gentamicin is an efficacious clinical antibiotic used against severe infections; however, the robust body of evidence indicates that the nephrotoxic side effect constrained its use. Virgin coconut oil (VCO) is an edible oil with growing human consumption and pharmacological effects. Our study has reported herein, for the first time, that VCO diet prevented the nephrotoxicity of gentamicin. Dietary supplementation of this oil could be beneficial in alleviating the nephrotoxic side effect of gentamicin in patients.


Subject(s)
Antioxidants , Pharmaceutical Preparations , Animals , Anti-Bacterial Agents/toxicity , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Caspase 3/metabolism , Coconut Oil , Gentamicins/toxicity , Humans , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/pharmacology , Oxidative Stress , Rats , Rats, Wistar , Signal Transduction
6.
J Integr Med ; 16(5): 342-349, 2018 09.
Article in English | MEDLINE | ID: mdl-30077645

ABSTRACT

OBJECTIVE: Vigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay. METHODS: Gastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined. RESULTS: Pretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GPX were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group. CONCLUSION: The study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Gastric Mucosa/drug effects , Nuts , Phytotherapy , Plant Extracts/therapeutic use , Stomach Ulcer/drug therapy , Vigna , Animals , Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Aspirin , Edema , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Gastrointestinal Agents/pharmacology , Gastrointestinal Agents/therapeutic use , Glutathione Peroxidase/metabolism , Hydrogen-Ion Concentration , Leukocytes , Male , Malondialdehyde/metabolism , Mucus/metabolism , Plant Extracts/pharmacology , Rats, Wistar , Severity of Illness Index , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stomach Ulcer/prevention & control , Superoxide Dismutase/metabolism
8.
Acta Inform Med ; 19(3): 153-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-23408661

ABSTRACT

Self-reported confidence before any examination in all levels of medical training is a product of previous experience, attitudinal inclinations overtime, degree of self subjection to tenets of professionalism and possibly, the inadvertent role of the medical school environment including colleagues, teachers and faculty members, comfort, satisfaction and psychosocial stability; which may be addressed as sub-factors that determine the level of preparedness. Let medical schools in Nigeria; adopt a continuous and regular assessment of students' self confidence before any minor or major examination, to monitor and ensure a certain psychological and academic level of preparedness among the students. This will avoid some cases of attrition resulting from self-doubt and lack of preparedness.

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