Olive leaf extract attenuates acrylamide-induced reproductive toxicity through reduced oxidative DNA damage and apoptosis associated with 8-OHdG and Caspase-3 in rats

Palladium chloride-induced testicular damage in rats: Histopathology, oxidative stress, ER stress, and Nrf2/HO-1 signaling and the protective role of quercetin.

The present study aimed to evaluate the protective potential of quercetin (Que), a flavonoid recognized for its antioxidant and anti-inflammatory activities, against palladium chloride (PdCl₂)-induced testicular toxicity. Twenty-four male Wistar rats were assigned to Control, Que (30 mg/kg), PdCl2 (8 mg/kg), and Que + PdCl2 groups for 28 days. PdCl₂ exposure was associated with reduced serum testosterone, LH, and FSH levels, impaired sperm quality, histopathological injury, increased oxidative stress and oxidative DNA damage, and diminished antioxidant capacity. These changes were accompanied by reduced Nrf2 and HO-1 levels, increased IL-6 and IL-1β concentrations, enhanced TNF-α immunoreactivity, and increased immunoreactivity of apoptosis and ER stress-related markers. Que co-treatment partly counteracted these alterations, improving redox balance, hormone levels, sperm parameters, and tissue morphology. Overall, the findings indicate that Que mitigates PdCl₂-induced testicular injury, and that this protection may be associated with antioxidant, anti-inflammatory, anti-apoptotic, ER stress-related, and Nrf2/HO-1-associated responses rather than direct proof of pathway activation.

Antioxidant efficacy of N-acetylcysteine against acrylamide-induced toxicity in Leydig cells by modulating p53/Bax/Caspase-3 pathway.

Acrylamide (Acr) is a widely encountered environmental and dietary toxicant known to induce oxidative stress and disrupt male reproductive function. Leydig cells, due to their high metabolic activity and mitochondrial dependence, are particularly vulnerable to redox imbalance. N-acetylcysteine (Nac), a thiol-containing antioxidant and glutathione precursor, has been extensively studied for its cytoprotective properties. However, its modulatory effects on Acr-induced toxicity in Leydig cells and its pharmacodynamic interaction profile remain incompletely characterized. In this study, TM3 Leydig cells were exposed to Acr in the presence or absence of Nac. Cell viability was assessed by MTT assay, and chemical interaction profiles were evaluated using ZIP, Bliss, and Chou-Talalay combination index analyses. Oxidative stress parameters, including intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant enzyme activities (SOD, CAT, GPx), and glutathione levels, were measured. Apoptotic responses were analyzed through double fluorescence staining, RT-qPCR of apoptosis-related genes (Bax, Bcl2, Casp3, Trp53), and Western blot analysis of CASP3 protein expression. Acr exposure significantly reduced cell viability, increased ROS and lipid peroxidation levels, suppressed antioxidant defenses, and activated the mitochondrial apoptotic pathway. Nac treatment markedly improved cell viability, restored antioxidant capacity, reduced oxidative stress markers, and suppressed p53/Bax/Casp3-mediated apoptotic signaling. Combination analyses revealed an antagonistic interaction profile, indicating that Nac biologically limits Acr-induced cytotoxicity. Collectively, these findings demonstrate that Nac exerts protective effects in Leydig cells by modulating redox homeostasis and mitochondrial apoptosis, suggesting its potential as a protective regulator against Acr-induced reproductive toxicity.

Effects of Ethanolic Extract of Monodora Myristica (Fresh and Roasted) on Lead Acetate Induced Infertility on Oxidative Stress Markers (SOD, MDA, And CAT) of Male Wistar Rats

Lead toxicity is a major environmental and public health concern associated with oxidative stress and male reproductive dysfunction. Accumulation of lead in testicular tissues has been reported to impair spermatogenesis through excessive generation of reactive oxygen species and depletion of endogenous antioxidant defenses. Monodora myristica, a medicinal plant widely used as a spice in Africa, possesses several pharmacological properties including potent antioxidant, free radical scavenging, metal chelating, and lipid peroxidation inhibitory activities attributed to its rich phytochemical composition. This study evaluated the effects of ethanolic extracts of fresh and roasted Monodora myristica seeds on oxidative stress markers in the testes of adult male Wistar rats exposed to lead-induced toxicity. A total of thirty adult male Wistar rats weighing between 120 g and 188 g were used for the study. The animals were divided into experimental groups comprising a normal control group, a lead acetate-treated group, groups administered lead acetate alongside fresh or roasted ethanolic seed extracts, groups pretreated with fresh or roasted extracts prior to lead exposure, and groups administered fresh or roasted extracts only. Lead acetate and the plant extracts were administered orally according to the experimental design. Biochemical analysis revealed significant alterations in oxidative stress markers following treatment. Administration of fresh and roasted Monodora myristica extracts produced significant effects on catalase (CAT) and malondialdehyde (MDA) levels, indicating modulation of antioxidant defense mechanisms and lipid peroxidation. However, no significant effect was observed on superoxide dismutase (SOD) activity. The observed antioxidant effects may be associated with the bioactive phytochemical constituents present in the extracts. The findings of this study suggest that ethanolic extracts of fresh and roasted Monodora myristica seeds possess antioxidant properties capable of ameliorating oxidative stress associated with lead-induced testicular toxicity in male Wistar rats. Therefore, Monodora myristica may have potential therapeutic value in the management of oxidative stress-related male reproductive disorders.

Protective Effects of Virgin Olive Oil Against Titanium Dioxide Nanoparticle-Induced Hepato-Renal Toxicity: Evidence from Oxidative Stress Biomarkers and Restoration of Antioxidant Enzyme Activities.

Targeting oxidative stress-NLRP3-apoptotic-steroidogenic axis in doxorubicin-induced testicular toxicity: protective efficacy of ferulic acid niosomes

Doxorubicin (DOX) is a commonly prescribed chemotherapeutic agent whose clinical application is limited by its toxicity to rapidly dividing organs, particularly the testes.This study explored the protective potential of ferulic acid-loaded niosomes (FA-NIO) against DOX-induced testicular dysfunction in rats and elucidated the underlying molecular mechanisms. Forty male rats were allocated into four groups: Group 1 was given saline, Group 2 was given DOX, Group 3 was given DOX + free FA, and Group 4 was given DOX + FA-NIO. Serum reproductive hormone levels, testicular oxidative stress indices, and the expression of genes and proteins relevant to NLRP3 inflammasome signaling, apoptosis (Bax and Bcl-2), and steroidogenesis (StAR, CYP11A1, and 3β-HSD) were assessed, along with histopathological changes in the testicular tissue. DOX administration significantly increased MDA (malondialdehyde) while suppressing antioxidant defences, accompanied by hormonal imbalance, severe histopathological damage, upregulation of Bax, NLRP3, and IL-1β, downregulation of Bcl-2, and inhibition of steroidogenic gene expression. On the other hand, these changes were partially mitigated in the DOX + free FA group. Notably, FA-NIO treatment reduced histopathological damage, normalised reproductive hormone levels, markedly increased steroidogenesis-related gene expression, suppressed apoptotic and inflammasome-related gene expression, and greatly restored antioxidant capacity. Compared with DOX + free FA, FA-NIO consistently demonstrated greater protective efficacy. In summary, FA-NIO targets oxidative stress-mediated apoptosis, attenuates NLRP3 inflammasome-related signaling, and restores steroidogenic function, thereby successfully attenuating DOX-induced testicular toxicity. These results suggest that FA-NIO may represent a promising nanotherapeutic strategy for attenuating chemotherapy-induced reproductive toxicity in a rat model.

Niosomal Hesperidin-Rich Citrus Peel Extract Attenuates Testicular Ischemia–Reperfusion Injury in Rats by Modulating p53- and Caspase-3-Associated Apoptotic Responses