Search Results (327)

The global surge in industrial waste generation has raised substantial concerns regarding occupational exposure to per- and polyfluoroalkyl substances (PFASs) and the associated adverse health effects. However, critical knowledge gaps remain regarding the relationships among size-resolved airborne particulate matter (PM)-bound PFASs, internal exposure, and early-stage health damage. We conducted a panel study at a waste recycling plant in southern China, collecting 15 size-resolved PM samples and 280 repeated first morning void urine samples from 20 workers over 45 consecutive days. Relationship between size-resolved PM-bound PFASs, internal exposure, and oxidative stress biomarkers (OSBs:8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA)) were analyzed using linear mixed-effects models. Our results indicate that short-chain PFASs predominated in both matrices. Intraclass correlation coefficients (ICCs) for urinary short-chain PFASs ranged from fair to excellent (ICC > 0.4). Notably, inhalation of PFASs in PM_2.1–10 correlate more strongly with internal exposure than those in PM_2.1. For the first time, we observed suggestive quantitative associations between OSBs and multiple short-chain PFASs in urine. More importantly, 8-OHdG levels were mainly correlated with PFASs in PM_4.7–5.8 and PM_9.0–10, with each unit increase in ln-transformed average daily intake (ADI) associated with a 10.2–12.6% increase in urinary 8-OHdG levels (p < 0.05). Similarly, MDA levels were primarily associated with PFASs bound to PM_5.8–9.0, with each unit increase in ln-transformed ADI corresponding to an 8.0–14.6% increase in MDA (p < 0.05). These findings are exploratory and warrant further confirmation in independent cohorts. Nevertheless, this study highlights the need for more exposure monitoring and health impact assessments regarding PM_2.1–10-bound short-chain PFASs among the occupational population. Full article

The protective effects of herbal feed additives Withania somnifera, Silybum marianum, Centella asiatica, and silymarin (administered at feed levels of 4000 ppm, 5000 ppm, 4600 ppm, and 25,000 ppm, respectively) against the toxic effects of ochratoxin A (OTA) (administered at 2 ppm) were investigated in 48 New Zealand White rabbits (37 days old) over an 80-day experimental period. A decrease in body weight was seen in rabbits exposed to OTA alone, but that decrease was less pronounced in rabbits receiving herbal supplements. The most severe lesions in OTA-treated rabbits were found in the liver, kidneys and spleen, while milder lesions were seen in the heart, intestine and lungs. The intensity of macroscopic, histopathological and biochemical changes was highest in rabbits exposed to OTA alone, followed by rabbits additionally supplemented with herbal additives, as evidenced by histopathological findings and serum levels of blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). The most pronounced protective effects of the herbal additives were observed in the kidneys and liver. Oxidative stress was significantly increased in rabbits exposed to OTA alone, as evidenced by elevated reactive oxygen species (ROS), nitric oxide (●NO), ascorbyl radicals (●Asc), protein oxidation (PO), procollagen type I alpha 1 (COL1A1), malondialdehyde (MDA), kidney injury molecule-1 (KIM-1), hydroxyproline (Hyp), advanced glycation end products (AEGs), heme oxygenase-1 (HO-1), catalase (CAT), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well decreased superoxide dismutase (SOD) and glutathione peroxidase-1 (GPx-1) activities, while protective effects were seen for all herbal additives, and better expressed for Centella asiatica and Silybum marianum. Full article

Oxidative stress contributes to heart failure (HF) progression by mechanisms that go beyond hemodynamic overload, including mitochondrial dysfunction, endothelial injury, inflammation, and fibrotic remodeling. This review evaluates the relationship between redox imbalance, Galectin-3 (Gal-3), fibrosis, and imaging findings in HF. Reactive oxygen species (ROS) generated by mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and xanthine oxidase may disturb calcium handling, impair mitochondrial function, activate fibroblasts, and promote ferroptosis. Biomarkers of oxidative injury and antioxidant reserve, including malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and circulating thiols, provide information complementary to natriuretic peptides. Experimental evidence supports a context-dependent role of Gal-3 in fibro-inflammatory remodeling, whereas circulating Gal-3 should be regarded as a complementary biomarker rather than as a direct measure of myocardial fibrosis. Echocardiography assesses functional remodeling through diastolic indices, myocardial deformation, and right ventricular–pulmonary arterial (RV–PA) coupling, while cardiac magnetic resonance characterizes focal scar and diffuse interstitial remodeling using late gadolinium enhancement, native T1 mapping, and extracellular volume fraction. Therapeutic strategies are increasingly shifting from nonspecific antioxidant supplementation toward targeting ROS sources and downstream pathways, with SGLT2 inhibitors emerging as clinically relevant agents with indirect redox-modulating effects. Integrated redox, fibro-inflammatory, hemodynamic, and imaging phenotyping may refine risk stratification, although prospective validation is required before routine implementation. Full article

Background: Neonatal open-heart surgery induces profound oxidative stress, yet its perioperative dynamics remain incompletely characterized. This study quantified urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane as markers of oxidative damage, and plasma α₁-microglobulin (A1M) as an endogenous antioxidant, while exploring the influence of pre- and intraoperative factors. Methods: In a prospective cohort of 40 term neonates with critical congenital heart defects undergoing open-heart surgery, serial urinary and plasma samples were collected perioperatively. Biomarker concentrations were analyzed using mixed-effects regression models to assess associations with postnatal age, sex, preoperative oxygenation, oxygen surge at bypass initiation, and cell-free hemoglobin in the prime solution. Results: Urinary 8-OHdG and 8-isoprostane increased following bypass separation; 8-OHdG remained elevated through postoperative days 0–2, while 8-isoprostane returned toward baseline by day 1. Plasma A1M declined at bypass initiation, recovered to preoperative levels at separation, and rose thereafter. Females exhibited higher A1M concentrations throughout. Longer time to surgery was associated with greater preoperative oxidative stress, and lower preoperative arterial pO₂ correlated with increased 8-isoprostane at bypass separation. No statistically significant associations were identified between intraoperative variables and biomarker levels, although the study was designed to be a hypothesis generating study and not powered to detect modest intraoperative effects. Conclusions: This exploratory study delineates distinct perioperative trajectories of oxidative stress and antioxidant response in neonates undergoing open-heart surgery, with surgical timing, preoperative hypoxemia, and sex emerging as relevant associations. No statistically significant associations were identified between intraoperative variables and biomarker levels; however, the study was hypothesis-generating in design and not powered to detect modest intraoperative effects. Full article

Background and Objectives: Oxidative stress is widely recognized as a key contributor to both the development and progression of chronic obstructive pulmonary disease (COPD), particularly during acute exacerbations (AECOPD). 8-Hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been insufficiently investigated as a systemic biomarker in this setting. This study evaluated the relationship between serum 8-OHdG levels, airflow limitation severity, and smoking status in patients hospitalized with AECOPD. Materials and Methods: We conducted a cross-sectional study including 176 patients admitted for AECOPD and stratified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. The study population comprised patients with comparable distributions of age, sex, smoking status, diabetes, cardiovascular comorbidities, and area of residence across GOLD categories. Serum 8-OHdG, leukocyte count, neutrophil percentage, C-reactive protein (CRP), fibrinogen, and procalcitonin were measured. Group comparisons, multivariable logistic regression analyses, and smoking-status subgroup analyses were performed. Results: Serum 8-OHdG levels increased significantly with advancing airflow limitation severity (p = 0.038), with higher concentrations observed in patients with GOLD 4 disease compared to GOLD 1–2 disease (p = 0.023). In multivariable analysis, 8-OHdG was the only biomarker independently associated with GOLD stage (OR = 2.44, 95% CI: 1.12–5.31, p = 0.025). Higher serum 8-OHdG levels were also independently associated with smoking status (OR = 1.20, 95% CI: 1.05–1.37, p = 0.022). Ever-smokers demonstrated significantly higher 8-OHdG concentrations than never-smokers in GOLD 1–2 and GOLD 3 disease, whereas procalcitonin levels were higher among never-smokers with advanced COPD. Conclusions: Serum 8-OHdG levels measured during AECOPD are associated with both airflow limitation severity and smoking status. These findings support the potential role of oxidative DNA damage as a clinically relevant component of COPD pathophysiology and suggest that serum 8-OHdG may represent a useful biomarker for disease characterization in patients experiencing acute exacerbations. Full article

Psychological stress can affect female reproductive function through behavioral, endocrine, ovarian, and oxidative mechanisms. Antioxidant supplements have therefore attracted attention for their potential to mitigate stress-related reproductive alterations. Coenzyme Q10 (CoQ10) is a lipid-soluble quinone involved in mitochondrial energy metabolism and is widely used as a dietary supplement. However, whether CoQ10 modulates female reproductive responses to repeated psychological stress remains unclear. Although water avoidance stress (WAS) is a well-established psychogenic stress model, its effects on female reproductive outcomes are still not fully defined. In this study, we examined how repeated WAS affects female reproductive outcomes and whether CoQ10 modifies these effects. Twenty-eight regularly cycling female rats were assigned to sham control, WAS, CoQ10, or WAS + CoQ10 groups. WAS was applied for 1 h/day for 10 days, and CoQ10 was administered orally at 100 mg/kg/day. Repeated WAS did not significantly alter sexual incentive motivation parameters, reproductive hormones, corticosterone, total antioxidant capacity (T-AOC), 8-hydroxy-deoxyguanosine (8-OHdG), or mast cell count under the present experimental conditions (all p > 0.05). However, WAS reduced male-directed active investigation time (p = 0.008) and male investigation preference ratio (p = 0.024), increased absolute ovarian and adrenal gland weights (p = 0.035 and p = 0.016, respectively), reduced primordial follicle number (p = 0.030), decreased germinative epithelium thickness (p = 0.017), lowered VEGF histoscore (p = 0.033) regardless of CoQ10 treatment, and reduced corpus luteum angiogenesis in animals not receiving CoQ10 (p = 0.030). CoQ10 reduced total investigation time toward the male (p = 0.032), male investigation preference ratio (p = 0.037), 17-β estradiol (E2) (p = 0.003), testosterone (p = 0.021), and germinative epithelium thickness (p < 0.001) regardless of WAS exposure. CoQ10 also decreased kisspeptin-1 levels under non-stressed conditions (p = 0.010), while increasing corpus luteum angiogenesis under stress conditions (p = 0.003). Overall, repeated WAS produced selective behavioral and ovarian alterations rather than broad reproductive dysfunction. CoQ10 was not associated with a broadly protective or uniformly beneficial profile in this model, and its endocrine, behavioral, and ovarian effects should be interpreted with caution. Full article

Plant-derived compounds have recently attracted considerable scientific attention due to their potential therapeutic applications, which are largely attributed to their antioxidant properties. Tert-butyl hydroperoxide (t-BHP) is a potent inducer of intracellular oxidative stress, generating reactive free radicals, which significantly contribute to hepatic and renal damage. Micromeria frivaldszkyana (M. frivaldszkyana), a Bulgarian endemic species, contains high levels of phenolic compounds, including linarin, rosmarinic acid (RA), chlorogenic acid, rutin, quercetin, naringenin, and apigenin. In this study, male Wistar rats received oral treatment for 5 days comprising saline, 250, 400, or 500 mg/kg of M. frivaldszkyana methanolic extract, 100 mg/kg RA, or 125 mg/kg silymarin. On the final day, 0.5 mmol/kg of t-BHP was injected intraperitoneally, and blood and liver tissue samples were collected 18 h later for biochemical and histological analysis. Liver and kidney function was evaluated using biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine (Cr), uric acid (UA)), indicators of oxidative stress (malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT)), and histopathology. Exposure to t-BHP resulted in significant hepatic and renal damage, including elevated serum markers, increased lipid peroxidation, and deoxyribonucleic acid (DNA) damage. Administration of 500 mg/kg M. frivaldszkyana markedly lowered elevated serum ALT and AST levels. The extract also significantly mitigated t-BHP-induced increases in serum Cr and UA. However, no significant increase in the levels of the antioxidant enzymes SOD and CAT or in GSH was observed at all tested doses. Malondialdehyde and 8-OHdG levels increased markedly following t-BHP exposure, whereas pretreatment with M. frivaldszkyana at all tested doses significantly ameliorated these oxidative alterations. These findings suggest that the methanolic extract of M. frivaldszkyana confers protective effects against t-BHP-induced toxicity, potentially through stabilisation of cell membranes, inhibition of lipid peroxidation, and reduction in DNA damage. The extract may therefore serve as a potential natural therapeutic agent against injuries caused by oxidative stress. Full article

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, whereas major depressive disorder is a common psychiatric condition with a substantial impact on quality of life; increasing attention has been given to oxidative and nitrosative stress as a potential biological link between these disorders. Methods: This narrative review synthesizes current evidence on molecular biomarkers of oxidative and nitrosative stress in AD and MDD and examines shared mechanisms within the skin–brain axis. Results: Across both conditions, studies consistently report increased markers of lipid peroxidation (e.g., malondialdehyde, 4-hydroxynonenal), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), and nitrosative stress, alongside impaired antioxidant defenses, particularly involving glutathione; these alterations are closely associated with chronic inflammation, cytokine signaling, mitochondrial dysfunction, and dysregulation of neuroimmune and hypothalamic–pituitary–adrenal axis pathways. Conclusions: Although the available evidence is heterogeneous and largely based on cross-sectional studies, limiting causal inference, the findings support a biologically plausible link between AD and depression mediated by shared redox pathways and highlight the need for further longitudinal and mechanistic research. Full article

Allergic diseases are complex conditions in which oxidative stress contributes to pathogenesis, yet the metabolic mechanisms linking oxidative stress to immunoglobulin E (IgE)-mediated responses remain unclear. This study analyzed 124 children at an 8-year follow-up, identifying those with eczema, rhinitis, and asthma. Oxidative stress markers and ¹H-nuclear magnetic resonance (NMR) blood metabolomic profiles were assessed to determine associations between metabolic pathways and atopic indices. Results showed that glutathione peroxidase (GPx) activity was significantly lower in seafood-sensitized children, while FeNO and mite-specific IgE were elevated in children with rhinitis (p < 0.01). Fractional exhaled nitric oxide (FeNO) correlated positively with allergen-specific IgE and negatively with 8-hydroxy-2′-deoxyguanosine (8-OHdG) (p < 0.01) and rhinitis-related methionine. Furthermore, seafood-specific IgE showed negative correlations with glucose and threonine (p < 0.01). Among 22 metabolites linked to atopy, threonine correlated positively with GPx (p < 0.01), while serine and mannose were associated with total antioxidant capacity (TAC). Pathway analysis revealed that branched-chain amino acid (BCAA) and glycine-serine-threonine metabolism intersected significantly with oxidative stress and atopic indices. In conclusion, a metabolomics-based approach highlights that oxidative stress-related BCAA and threonine pathways are central to the metabolic signature of childhood allergies, providing potential targets for future therapeutic interventions. Full article

Background and Objectives: Migraine is a chronic, throbbing type of headache that affects large populations worldwide. This condition is associated with neuroinflammation. Materials and Methods: In this study, polymorphism analyses were performed by KASP PCR. Serum interleukin-6 (IL-6) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured using kits based on the enzyme-linked immunosorbent assay (ELISA) principle. Results: In the APE1 Asp148Glu (rs1130409) gene polymorphism analysis, the frequency of the mutant G (Glu) allele was 93.1% and 48.0% in the control and migraine populations, respectively, while the frequency of the wild-type T (Asp) allele was 6.9% and 52.0% (p < 0.001). The frequency of the T/T (Asp/Asp) genotype was high in the migraine group (p < 0.001), while the frequency of the G/G (Glu/Glu) genotype was higher in the control group at 86.2%, compared to the migraine group (p < 0.001). The total frequency of the T/G+ G/G (Asp/Glu+Glu/Glu) composite genotype was determined to be 65.9% in the control group and 34.1% in the migraine group (p < 0.001). There was no statistical difference in allele and genotype frequency between the control and migraine groups for the XRCC1 Arg399Gln (rs25487) gene polymorphism. Serum 8-OHdG and IL-6 levels were comparable between the groups, with no statistically significant differences observed. Conclusions: Future studies with larger and more homogeneous populations are needed to further elucidate the potential interactions between inflammatory processes and DNA damage in migraine. Consideration of attack duration and environmental exposures may improve interpretation of biomarker variability. Expanding the analysis to additional DNA repair gene polymorphisms may also contribute to a better understanding of the molecular background of migraine and the evaluation of potential biomarkers. Full article

Background/Objectives: We aimed to evaluate the efficacy and safety of a short-term dietary intervention using trigonelline-rich Sakurajima radish on vascular endothelial function in patients with metabolic syndrome (MetS). Methods: In this multicenter, open-label, randomized, three-period crossover phase IIb trial, 21 patients with MetS were assigned to three 14-day sequences (Sakurajima radish powder, Aokubi radish powder, and a usual diet), separated by 14-day washouts. The primary outcome was flow-mediated dilation (FMD). Key Secondary outcomes included blood pressure (BP), urinary nitric oxide metabolites (NOx), and the oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG). Results: Sakurajima radish did not improve FMD versus the usual diet (p = 0.58) or Aokubi radish (p = 0.59), although a significant negative carryover effect following the Aokubi period likely confounded this estimation. Despite successfully stimulating NO production (elevated urinary NOx, p = 0.03), the intervention paradoxically increased oxidative stress (elevated 8-OHdG/creatinine, p = 0.02) and significantly elevated systolic BP compared with the usual diet (+9.67 mmHg, p = 0.03) and Aokubi radish (+8.86 mmHg, p = 0.04). Conclusions: Sakurajima radish does not appear to improve endothelial function in patients with MetS within the constraints of this short-term crossover design. Importantly, the unexpected negative carryover effect inherently limits the interpretability of this primary FMD outcome, as it may have masked potential physiological benefits. Despite boosting NO production, the intervention paradoxically exacerbated systemic oxidative stress and elevated systolic BP. These findings suggest that in the pro-oxidant environment of MetS, NO-boosting functional foods may induce unintended adverse hemodynamic responses, underscoring the need for careful risk–benefit evaluation and parallel-group trial designs in this specific population. Full article

Doxorubicin (Dox) is a cornerstone in the treatment of pediatric acute lymphoblastic leukemia (ALL), but its use is limited by dose-dependent cardiotoxicity. Oxidative stress, arising from mitochondrial dysfunction, enzymatic generation of reactive oxygen species, and cardiotoxic metabolites, has been implicated as a central mechanism, with interindividual variability partly influenced by genetic factors. This study evaluated oxidative DNA damage 8-hydroxy-2′-deoxyguanosine (8-OHdG) as an integrative marker of redox-related pathways in Dox-induced cardiotoxicity. In a prospective case–control study, 93 pediatric patients with ALL treated with Dox and 63 controls were included. Cardiotoxicity was assessed by serial echocardiography, and 8-OHdG levels were measured by ELISA. Genotyping of ABCC1 rs3743527, NCF4 rs1883112, and CBR3 rs1056892 was performed, and multivariable analyses were conducted. Dox-treated patients showed higher 8-OHdG levels than controls, and patients with cardiotoxicity (n = 11) had higher levels than those without. A higher frequency and severity of cardiotoxicity was observed in female patients, although this finding should be interpreted cautiously. Although allele frequencies did not reach statistical significance, distinct distribution patterns were observed between groups. These findings suggest that 8-OHdG may function as an integrative marker of redox dysfunction associated with Dox-induced cardiotoxicity. Full article

Background/Objectives: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory disease of the breast that may present with recurrent and treatment-resistant courses and can clinically and radiologically mimic breast cancer. Despite its benign nature, IGM may significantly impair quality of life, and its underlying pathophysiology remains unclear. This study aimed to evaluate oxidative stress and DNA damage in patients with IGM. Methods: In this prospective case–control study, 28 patients with clinically and histopathologically confirmed idiopathic granulomatous mastitis who had not received corticosteroid or immunosuppressive therapy within the previous six months were enrolled. An age-matched control group of 27 healthy women was included. Venous blood and urine samples were collected for the assessment of total oxidant status (TOS), total antioxidant status (TAS), and calculation of the oxidative stress index (OSI). Mononuclear leukocyte DNA damage was evaluated using the alkaline Comet assay, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured by ELISA. Sociodemographic data, laboratory and imaging results of the patients were also evaluated. Results: The mean ages of the patient and control groups were 37.3 ± 5.3 and 35.4 ± 8.6 years, respectively, with no significant difference (p = 0.081). Patients exhibited significantly higher inflammatory markers and oxidative stress parameters, including TOS, OSI, and urinary 8-OHdG (p < 0.05), whereas TAS did not differ between groups (p = 0.534). Comet assay analysis demonstrated significantly increased tail intensity (%) and tail moment in the patient group (p = 0.029 and p = 0.016). Conclusions: IGM is associated with increased oxidative stress and mononuclear leukocyte DNA damage. These findings suggest that oxidative stress-induced DNA damage may play a role in the pathophysiology of IGM and highlight the potential value of antioxidant-based therapeutic strategies as adjunctive treatment options. Full article

Pressure ulcers are chronic wounds characterized by repeated ischemia–reperfusion injury, persistent inflammation, and redox imbalance, in which excessive production of reactive oxygen species (ROS) contributes to delayed healing. Thus, debridement is an essential therapeutic procedure for removing necrotic tissue and biofilm, thereby reconstructing the wound microenvironment. Recent experimental studies suggest that molecular hydrogen may improve wound healing through attenuation of oxidative stress and modulation of inflammatory responses, while debridement represents a dynamic intervention phase in which redox imbalance may transiently develop. Here, we propose the hypothesis that the use of hydrogen-enriched saline as an irrigation solution during hydrosurgical debridement may attenuate excessive redox imbalance and stabilize the wound microenvironment during this dynamic intervention phase. Such intra-procedural modulation may facilitate the transition from inflammation to the proliferative phase of wound healing, thereby promoting tissue repair. This approach is expected to attenuate the transient oxidative burst following debridement, as reflected by reductions in redox-related biomarkers in the wound environment, including ROS levels and oxidative damage markers such as 8-hydroxy-2′-deoxyguanosine and lipid peroxidation products, with relative decreases in these biomarkers compared with conventional debridement, potentially consistent with reductions observed in preclinical oxidative stress models. These findings are consistent with findings from previous experimental studies demonstrating attenuation of oxidative stress markers following hydrogen administration. This hypothesis introduces a novel therapeutic concept, redox modulation during the debridement process, offering a practical strategy for integrating hydrogen-based therapy into existing wound management without altering current surgical techniques. Full article

Pesticide exposure is a plausible but incompletely characterized contributor to kidney injury. This review integrates current clinical, epidemiologic, experimental, and mechanistic evidence on pesticide-related nephrotoxicity, focusing on glyphosate-based herbicides, paraquat, organophosphate insecticides, and atrazine. A structured search of PubMed and Web of Science identified English-language studies published between January 2015 and February 2026. Of 635 records screened, 61 human studies were retained for full-text evaluation, and relevant animal, in vitro, and regulatory sources were additionally reviewed for mechanistic interpretation. Across pesticide classes, the proximal tubule emerged as the most consistent renal target, although downstream pathways differed, including oxidative stress, mitochondrial dysfunction, transporter disruption, endoplasmic reticulum stress, inflammation, apoptosis, ferroptotic signaling, and fibrotic remodeling. Human evidence was strongest for acute kidney injury following severe poisoning, whereas associations between chronic occupational or environmental exposure and chronic kidney disease or end-stage renal disease were more limited and heterogeneous. Biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), β₂-microglobulin, cystatin C, interleukin-18 (IL-18), cytochrome c, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) often detected early tubular stress before abnormalities appeared in conventional renal indices. Overall, pesticide nephrotoxicity is best conceptualized as a spectrum of mechanism-specific tubular injury signatures, supporting a shift toward biomarker-informed early detection, improved hazard identification, and more mechanistically grounded risk assessment. Full article