Quercetin attenuates busulfan-induced testicular and epididymal toxicity via modulation of oxidative stress, inflammatory cytokines, and apoptotic markers in rats.

Eugenol mitigates glyphosate-induced testicular toxicity via modulation of oxidative stress, ER stress, RAGE/NLRP3 and PI3K/AKT signaling pathways in rats.

Effects of exhaustive exercises, with different intensities, on oxidative stress markers in rat plasma and skeletal muscle

Exposure to various environmental and lifestyle-dependent factors such as heavy and trace metals, hydrocarbons, ethylene glycol ethers, obesity, tobacco, alcohol and recreational drugs etc. have been identified to cause reproductive toxicity in men. A number of toxicants affect spermatogenesis leading to poor semen quality affecting fertility in such men, primarily through the mechanism of oxidative stress. In the male reproductive system, oxidative stress is brought about either by excessive production of extrinsic free radicals or by reduced activity of intrinsic antioxidants thereby disrupting the redox balance. Discrete measures of reactive oxygen species, total antioxidant capacity, and post hoc damage suggest an ambiguous relationship between the redox system and male fertility. Antioxidants work by donating electrons to the oxidants, thereby reducing the chances of oxidants to acquire electrons from other nearby structures and cause oxidative damage. Oxidation-reduction potential (ORP) measures this relationship between oxidants and antioxidants in semen. The MiOXSYS system used to measure ORP requires a small volume (~30 µl) of liquefied semen and the measurement is completed in less than 5 min. The galvanostat-based analyzer uses electrochemical technology to measure the ORP in millivolts (mV) which is then normalized to express as mV/106 sperm/mL. The role of ORP as a surrogate marker to conventional semen quality parameters is a current topic of investigation by a number of researchers and clinicians. It can be measured in semen and seminal plasma up to 2 h of liquefaction. ORP correlates negatively with conventional as well as advanced semen quality parameters, including sperm concentration, total sperm count, total motile sperm count, motility, morphology, and DNA fragmentation thus confirming the association of oxidative stress with male factor infertility. ORP values can differentiate the degree of oxidative stress-induced male infertility. A number of clinical studies involving cohorts of men from USA, Qatar and India have established seminal ORP cut-off values to distinguish fertile men from infertile patients. Monitoring ORP levels may help predict treatment efficacy in patients as higher ORP values are indicative of the progression of infertility. It can also be measured in cryopreserved semen samples, which is important in predicting the success of assisted reproductive techniques (ART). A recent ART study reported higher clinical pregnancy rate in infertile men with low seminal ORP in comparison to patients with high ORP. Findings of recent clinical investigations indicate ORP as a novel, independent and robust diagnostic marker of seminal oxidative stress that should find its place in the male infertility workup algorithm.

Various experimental and clinical studies strongly support a cigarette smoke-heart disease association and suggest possible mechanisms, unfortunately, the involvement of genetic modulations remain unexplored. Thus, the main aim of the current study was to evaluate the effects of sub-chronic cigarette smoke exposure on the mRNA expression of cardiac hypertrophy genes, cytochrome P450 (CYP) enzymes, and the oxidative stress markers in heart rats. For this purpose, Wistar albino rats were exposed to increasing doses of passive cigarette smoke 2, 4, 8, and 24 cigarettes per day for 7 consecutive days. The mRNA expression of fifteen cardiac genes was determined using real-time polymerase chain reaction. Our results showed that the levels of hypertrophic genes; atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain were significantly induced, whereas the anti-hypertrophic gene α-myosin heavy chain was dramatically inhibited, in heart tissues of passive-smoke-exposed groups compared with normal-control groups. This was accompanied with a significant induction of CYP enzymes; CYP1A1, CYP2C11, CYP2E1, and CYP3A2, and the expression of oxidative stress genes, heme oxygenase 1, catalase, cyclooxygenase, and glutathione S-Transferase. The ability of cigarette smoke to induce cardiac hypertrophic genes, CYPs enzymes, and oxidative stress, collectively explore the molecular mechanism of cigarette smoke-induced cardiac diseases and brings further investigative attention to the public health issue of the injurious effects of chronic passive smoke exposure. In conclusion, sub-chronic environmental tobacco smoke exposure increases the incidence of cardiovascular diseases through modulation of cardiac genes.

Objectives: The current study was designed to evaluate protective role of the ethanolic fenugreek seed extract (FSE) and potentiating its effects with nitric oxide (NO) modulators in experimental arthritis and its comparison with the standard drug methotrexate. Materials and Methods: The FSE was prepared using standard procedures. Fifty-four male Wistar rats were equally distributed into nine groups of six animals in each group. Rheumatoid arthritis was induced by administration of complete Freund’s adjuvant (CFA) in sub-plantar region of rt. hind paw. FSE alone and with L-arginine or Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) were administered on day 10 of CFA inoculation, i.p. Animals were evaluated for arthritic parameters, cytokines and oxidative stress markers estimation. Statistics: The data were analysed by two-way ANOVA followed by Newman Keul’s post hoc test for inter group analysis by GraphPad Prism 6.0 and P < 0.05 was taken as significant. Results: Adjuvant inoculated rat shows significant increase in arthritic and inflammatory parameters as well as oxidative stress biomarkers in serum, paw homogenates and joint synovial fluid. CFA inoculation significantly decreased anti-inflammatory cytokine-10 and SOD activity. These adjuvant-induced arthritic changes were significantly attenuated by ethanolic FSE administration from 10 to 28 days. These results are comparable to standard drug methotrexate. NO modulators further potentiated protective effects of FSE when given in combination. These results were more prominent when ethanolic seed extract was given with iNOS inhibitor, L-NAME. Conclusion: These findings suggest that FSE shows protective effects in CFA induced arthritic changes that may be mediated through pro-inflammatory/anti-inflammatory cytokines imbalance and it is associated with modulation of oxidative stress and NO-signalling.

ObjectiveReproductive toxicity has been greatly linked with Highly Active Antiretroviral Therapy (HAART) use. This study investigated the effects of Moringa oleifera Leaf Extract (MOE) on HAART-induced testicular toxicity in adult male Wistar rats.MethodsTwenty adult male Wistar rats (150-200 g) were assigned into four groups (n=5). Group A received distilled water; Group B received (orally) 200 mg/kg BW HAART only; Group C received (orally) 200 mg/kg BW HAART and 100 mg/kg BW MOE (low dose group) and Group D received (orally) 200 mg/kg BW HAART and 300 mg/kg BW MOE. At the end of the 28-day experiment, body and testicular weights were measured; serum and testis obtained were subjected to hormone profiling, biochemical and histological studies.ResultsHAART caused a significant decrease in body and testicular weight, testicular distortion and spermatogenic cell disorganization, altered semen quality and function, hormonal profiles, and oxidative stress markers (SOD, CAT, GSH) were significantly decreased with the concurrent increase in MDA level. However, treatment with MOE improved sperm parameters, testis morphology, antioxidants markers, and hormones assessments.ConclusionsThe exposure to HAART produced marked testicular toxicity, ameliorated using Moringa oleifera leaf extract, thereby preserving testicular physiological function and morphology.

Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.

The main aim of this study was to assay the testicular H2 S levels in the varicocele rat model and then to investigate the protective effects of NaHS on morphometric changes, sperm parameters, oxidative stress and apoptosis markers in rat's testis. D,L-propargylglycine (PAG) was administrated to show the effects of cystathionine γ-lyase enzyme (CSE) inhibition in the varicocele. Rats were assigned to four groups: (a) Sham, (b) varicocele, (c) varicocele+PAG and (d) varicocele+NaHS. Animals in varicocele+NaHS group received 30µmol/L NaHS in drinking water for 56days. In the varicocele+PAG group, animals received PAG 19mg/kg twice a week. Morphometric assessment, oxidative stress markers, testicular H2 S levels, sperm parameters, TUNEL assay and expression of Bax/Bcl2 were evaluated at the end of experiment. Testicular H2 S levels were significantly decreased in varicocele group. NaHS significantly improved sperm parameters, morphometric characteristics and oxidative stress compared to varicocele group. Oxidative stress status deteriorated in the PAG group compared to the varicocele group. This study showed that a low testicular H2 S level might play a critical role in male infertility. Thus, NaHS administration may be a promising treatment strategy for male infertility in varicocele. In addition, CSE may not be the only important enzyme in testicular H2 S production.

Effects of BDE-99 on hormone homeostasis and biochemical parameters in adult male rats

BackgroundThere is an increasing concern over acute exposure of amphetamine and its derivative such as 3,4-methylenedioxymethamphetamine (MDMA) on male reproductive toxicity. Supplementary vitamins can reduce the oxidative stresses and repair the damages on reproductive organs. This experimental study was conducted to evaluate the effects of folic acid (FA) on reproductive indices, the antioxidant enzyme activities, and histological changes of testis on adult male rats treated by MDMA.MethodsThis experimental study was conducted on adult male Wistar rats. Animals were divided into 4 groups: control, MDMA, FA, and MDMA + FA. Animals received a dose of 10 mg/kg of MDMA and 1 mg/kg of FA for 7 or 14 days. Rats were anesthetized and sperm quality parameters (number, concentration, motility, and morphology), spermatogenesis indices [the mean seminiferous tubule diameter (MSTD), spermiogenesis index (SI), repopulation index (RI), and tubular differentiation index (TDI)], changes on testicular structure, antioxidant enzyme activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) beside serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. Data were analyzed, using the one-way analysis of variance (ANOVA) and SPSS software.FindingsMDMA (both 7 and 14 days) caused significant changes in sperm quality (P < 0.001), spermatogenesis indices (P < 0.001), testicular histopathology, and level of LH, FSH, testosterone beside the antioxidant enzyme activities (SOD, CAT, and MDA) (P < 0.001). Supplementation of FA in association with MDMA partially reversed these parameters and made them close to the control group.ConclusionThe results suggested that FA could reduce the adverse effect of MDMA on reproductive ability in adult male rats.

Background: Long and repeated heating causes multiple physical and chemical changes in oil, which may result in serious biological damages upon consumption. Objectives: This study investigated the effects of heated oils used in fast food restaurants on metabolic, inflammatory, and oxidative stress markers in rats. Methods: The experimental clinical study was performed during summer 2016 in Shiraz, Iran. For 13 weeks, 32 Sprague-Dawley rats received one of the four diets: Group 1: basal diet mixed with 15% w/w heated oil containing total polar compounds (TPC) = 12.5% (TPC 12.5); Group 2: basal diet with 15% unheated oil used in group 1 (control TPC 12.5); Group 3: basal diet with 15% heated oil with TPC = 35% (TPC 35); and Group 4: basal diet with 15% unheated oil used in group 3 (control TPC 35). At weeks six and 13, blood samples were collected for determination of fasting glucose, lipid profile, liver enzymes, and inflammatory and oxidative stress markers. Blood pressure was measured on the 13th week. Histopathological examination of liver slices was performed after euthanization of rats. Statistical analysis was done using the SPSS software. Results: On the 13th week, the TPC 35 group had higher plasma glucose (+40.4 mg/dL, P < 0.05), triglycerides (+13.6 mg/dL, P < 0.05), aspartate transaminase (+34.3 U/L, P < 0.05), interleukin-1β (+453 pg/L, P < 0.01), and blood pressure (+16/5 mmHg, P < 0.05) than the control and higher glucose (+59.3 ng/L, P < 0.001), aspartate transaminase (+55.5 U/L, P < 0.05), total cholesterol (+6.5 mg/dL, P < 0.05), and 8-isoprostane (+8.5 mg/dL, P < 0.05) than the values on week six. On the 6th week, Low Density Lipoprotein (LDL)-cholesterol was higher in the TPC 35 group than TPC 12.5 (+4.0 mg/dl, P < 0.05) and the level of serum malondialdehyde was higher in the TPC 35 than the control (+0.49 μmol/L, P < 0.001). On the 13th week, more histological changes were observed in rats of the heated oil groups. Conclusions: Long-term consumption of fried foods from fast food restaurants may have detrimental impact on blood pressure, serum glucose and lipids, inflammatory and oxidative stress markers, and liver histology.

Atorvastatin influences oxidative stress markers in hypercholesterolemic rats

Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1mg/kg bw of LTC for 7, 30, 45, and 60days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as potential biomarker in human biomonitoring studies.

Nanoparticles (NPs) have gained increasing attention due to their unique physicochemical properties and broad applications. However, concerns about their potential toxicity, particularly reproductive toxicity, have emerged. Silica dioxide nanoparticles (SiO₂-NPs) are among the most commonly used NPs and have been linked to adverse effects on male reproductive health. This study aimed to evaluate the potential ameliorative effect of thymol, a natural monoterpene phenol with antioxidant and anti-inflammatory properties, against SiO₂-NPs-induced reproductive toxicity in male rats. Twenty-four adult male Sprague-Dawley rats were randomly assigned to four groups: control, SiO₂-NPs-treated (10 mg/kg body weight, intraperitoneally), thymol-treated (30 mg/kg body weight, orally), and SiO₂-NPs + thymol co-treated. Treatments were administered daily for 56 days. Male reproductive performance was evaluated through sexual behavior assessment, sperm characteristics, reproductive hormone levels, oxidative stress markers, inflammatory biomarkers, gene expression analysis, and histopathological examination of testicular tissue. Results revealed that SiO₂-NPs significantly impaired reproductive performance, indicated by reduced sperm motility, viability, and count, along with increased sperm abnormalities. Thymol co-administration significantly restored testosterone levels and partially normalized elevated LH and FSH levels caused by SiO₂-NPs, indicating endocrine protection. Moreover, SiO₂-NPs induced oxidative stress, elevated pro-inflammatory cytokines (TNF-α and IL-6), and disrupted the expression of key genes associated with oxidative stress response (NRF2), apoptosis (BAX, BCL-2), steroidogenesis (STAR, CYP11A1), and spermatogenesis (PRM1, GATA4). Thymol co-administration with SiO₂-NPs significantly mitigated these adverse effects by restoring antioxidant levels, reducing inflammation, and improving gene expression and the histological architecture of the testes. The findings suggest that thymol has a promising protective role against SiO₂-NPs-induced male reproductive toxicity through its antioxidant and anti-inflammatory actions.

Objective: To compare the effect of complete and partial renal capsulotomy on the renal function tests and oxidative stress markers in rats undergoing ischemia-reperfusion injury. Design: Randomized controlled experimental study. Animals: A 60 Spraque-dawely rats weighing 180 ± 50 g. Procedures: Rats were divided into 3 groups in triplicate (6 each). In addition, 6 rats were subjected to blood and renal tissues sampling for estimation of normal parameters. Group 1 (Positive control): ischemia reperfusion (IR) injury; Group 2: Complete capsulotomy + I R; Group 3: Partial capsulotomy + IR. Six rats from each group were sacrified at 2, 7 and 14 days post- surgery. Results: The complete capsulotomy induced a significant decrease in the serum creatinine at 2 and 7 days post- capsulotomy in comparison with partial capsulotomy (P &lt; 0.05), whereas at 14 days, the partial capsulotomy induced the significant decrease (P &lt; 0.05). Complete capsulotomy showed a significant improvement in creatinine clearance in comparasion with partial capsulotomy at 2, 7 and 14 days post- surgery (p&lt;0.05). At 2 and 7 days, BUN of IR+ Capsulotomy group showed a significant decrease (P &lt; 0.05) compared to the other groups, while at 14 days partial capsulotomy, the serum BUN reached to the normal value. Serum sodium level showed a significant decrease (P &lt; 0.05) at 2 days after partial capsulotomy, and at 14 days after complete capsulotomy (P &lt; 0.05). Nitric oxide level in IR + partial capsulotomy group showed a significant decrease at 7 and 14 days (P &lt; 0.05). Results of MDA of IR+ partial capsulotomy groups showed a significant decrease (P &lt; 0.05) compared to the IR+ compete capsulotomy groups at 2,7 and 14 days. Conclusion and clinical relevance: The partial capsulotomy ameliorates could improve serum creatinine, BUN and could lower the oxidative stress at 14 days. Partial capsulotomy could also improve the renal tissues at both short and long-term. So this study indicates the importance of the presence of intact renal capsule for ischemic acute kidney injury.