Lycopene alleviates zearalenone-induced endometrial ferroptosis in early pregnant sows by activating the Nrf2/GPX4 pathway.

Lycopene-mediated mitigation of cadmium-induced nephrotoxicity in broilers is associated with restoring mitochondrial homeostasis.

Carotenoids have direct antioxidant and anti-inflammatory health benefits. Owing to their low bioavailability, they also reach the colon, yet their microbiome interactions remain poorly characterized. We investigated how β-carotene (BC), lutein (LU), lycopene (LY) and zeaxanthin (ZE), at biological relevant doses (between 1 and 60mg/d), impact composition and metabolite production of irritable bowel syndrome (IBS) and overweight (OW) adult gut microbiota using the ex vivo SIFR® fermentation system (systemic intestinal fermentation research). Fresh fecal samples were collected from 12 donors (n = 6 per cohort) and incubated for 24h under anaerobic conditions, with carotenoids administered alone or in combination with prebiotic inulin (IN, tested at 2.5g/day). We observed phenotype-specific microbiota characteristics for each cohort at baseline. Carotenoids alone had only minor effects but in combination with prebiotic inulin significantly altered community composition (Bray-Curtis dissimilarity, P < 0.05) and enhanced short-chain fatty acid (SCFA) production. Most carotenoids increased butyrate production vs. inulin alone with ZE (at 2mg/d) in IBS (+ 7.6%) and LU (at 60mg/d) in OW (+ 8.0%) showing the strongest effects (padjusted<0.10). In contrast, LY (at 45mg/d) uniquely increased acetate (+ 3.5%) and propionate (+ 8.0%) at the expense of butyrate (-7.5%, padjusted<0.10) when compared vs. inulin only. Changes in SCFA correlated with carotenoid- and cohort-specific shifts in the abundance of Bifidobacterium, Alistipes, Akkermansia, Faecalibacterium and Coprococcus. ZE also enhanced the effect of inulin on the health-related metabolites 3-phenyllactic acid (PLA) and 2-hydroxyisocaproic acid (HICA), particularly IBS subjects (padjusted<0.20). Antioxidant carotenoids may support anaerobic gut microbes including dominant butyrate producers and counteract phenotype-specific dysbiosis, potentially offering novel dietary approaches for IBS and obesity-associated dysbiosis. As these effects were observed when carotenoids were combined with inulin, carotenoids may have greater impacts when consumed as part of a fiber-rich diet, reflecting their natural occurrence in plant-based foods.

Cisplatin (Cis) is a widely utilized chemotherapy drug for managing various cancers, but its efficacy is limited by nephrotoxicity, which frequently results in kidney fibrosis. Oxidative stress, inflammation, and the fibrotic transforming growth factor beta/small mothers against decapentaplegic (TGF-β/SMAD) pathway are among the underlying mechanisms. Long-term exposure to Cis causes apoptosis, extracellular matrix deposition, and fibrosis. Fluvoxamine (FLV), a selective serotonin reuptake inhibitor and sigma‑1 receptor agonist, lycopene (LYC), a carotenoid antioxidant, and their combination showed a novel protective influence on kidney fibrosis in male albino rats induced by administering Cis (7 mg/kg) by intraperitoneal (IP) injection once weekly for 4 weeks. FLV (5 mg/kg), LYC (10 mg/kg), and their combination were administered orally (PO) once daily for four weeks. Treatment reduced blood urea nitrogen (BUN), serum creatinine (S.cr), nuclear factor kappa B (NF-κB), microRNA-21 (miR-21) levels, and the pro-apoptotic response reflected by decreased Bcl-2-associated X protein (Bax) immunoreactivity while enhancing antioxidant activity. They also attenuated fibrosis markers, including TGF-β1, SMAD3, collagen I (Col-I), and alpha-smooth muscle actin (α-SMA). FLV and LYC effectively attenuated Cis-induced kidney fibrosis through antioxidant, antiapoptotic, and antifibrotic mechanisms. These findings may provide a new therapeutic approach to counter Cis-induced nephrotoxicity in clinical settings.

Lycopene ameliorates swainsonine-induced autophagy in rat renal tubular epithelial cells via the endoplasmic reticulum stress UPR pathway.

Soybean protein complexes as diglyceride nanostructured lipid carriers for lycopene delivery: preparation via metal-phenol network formation.

Oxaliplatin (OXI), a platinum-based chemotherapeutic agent commonly used in colorectal Cancer treatment, has been linked to significant nephrotoxicity involving apoptosis, endoplasmic reticulum (ER) stress, inflammation, oxidative stress, and autophagy. This study investigated the potential mechanisms involved in kidney damage caused by OXI and explored the renoprotective effects of lycopene (LP) in renal tissues of rats. Biochemical analyses revealed that OXI administration led to elevated serum urea and creatinine levels, increased lipid peroxidation (MDA), and decreased antioxidant defense (SOD, CAT, GPx, GSH), accompanied by suppression of the Nrf-2/HO-1 pathway. Inflammatory markers such as NF-κB, IL-1β, COX-2, TNF-α, and iNOS were significantly upregulated, along with ER stress-related genes (GRP78, ATF6), apoptotic markers (p53, Bax, Bcl-2), and key mediators of autophagy (Beclin-1, JNK). Additionally, Western blot and immunohistochemistry results indicated increased expression of AKT, mTOR, and PI3K proteins in the OXI group, suggesting altered survival signaling. LP treatment ameliorated these pathological alterations by restoring antioxidant enzyme activities, downregulating proinflammatory and proapoptotic signals, mitigating ER stress and autophagy activation, and reducing PI3K/AKT/mTOR protein expression. These findings demonstrate that LP exerts a renoprotective effect against OXI-induced kidney injury through multi-targeted molecular mechanisms, including modulation of inflammation, oxidative stress, autophagy, apoptosis, and survival signaling pathways.

Natural pigment lycopene (LYC), a carotenoid, possesses antioxidant, anti-apoptotic, anticancer, and immunoenhancing properties. During in vitro culture, this substance protects oocytes and early embryos from damage caused by reactive oxygen species (ROS), thereby enhancing the in vitro maturation (IVM) rate of oocytes and the developmental competence of early embryos. This study aimed to investigate the effects of supplementing different concentrations of LYC (0, 5, 10, and 15 μM) during in vitro culture of sheep oocytes and early embryos on their developmental competence. In contrast to the control group, the 5 μM LYC treatment group displayed a marked increase in the first polar body extrusion rate and the extent of cumulus cell expansion, as well as a significantly higher proportion of normal spindle assembly in sheep oocytes, but 15 μM LYC appeared to negatively affect oocyte maturation. Relative to all other experimental groups, the 5 μM LYC treatment group displayed significantly elevated rates of cleavage and blastocyst rate during early in vitro embryonic development. The levels of ROS in mature oocytes and early embryos were significantly decreased, whereas the GSH level was significantly elevated. Furthermore, LYC treatment significantly enhanced mitochondrial activity and markedly elevated the mitochondrial membrane potential (MMP) in mature oocytes and early embryos. Moreover, the total cell number of blastocysts was significantly increased. Moreover, in early embryos, the transcript levels of genes associated with both oxidative stress and apoptosis were favorably regulated. In conclusion, LYC supplementation boosted the rates of oocyte maturation and blastocyst formation in sheep, while elevating the developmental capacity of early embryos.

Hexavalent chromium [Cr(VI)] is a well-established environmental nephrotoxicant that induces renal injury. Lycopene (LYC), one of the most potent naturally occurring antioxidants found in plants, has demonstrated protective effects against various forms of oxidative damage; however, its therapeutic role and underlying mechanisms in Cr(VI)-induced nephrotoxicity remain unclear. In this study, eighty female SPF-grade ICR mice were randomly assigned to four groups: control (Con), LYC, Cr(VI), and LYC + Cr(VI), and treated for 28 days. The results demonstrated that LYC significantly alleviated Cr(VI)-induced renal dysfunction and structural damage. Cr(VI) exposure markedly increased malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) levels while suppressing antioxidant enzyme activities, including catalase (CAT), glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD). In contrast, LYC supplementation effectively restored antioxidant capacity and activated the Nuclear factor-erythroid 2-related factor 2(Nrf2) signaling pathway. Moreover, LYC mitigated Cr(VI)-induced mitochondrial dysfunction by suppressing excessive activation of mitochondrial fission-related proteins (Fis1, Drp1, and MFF) and PINK1/Parkin-mediated mitophagy. Notably, LYC co-treatment enhanced the expression of key mitochondrial biogenesis regulators, including Sirt1 and PGC-1α, in renal tissue. Collectively, these findings indicate that LYC protects against Cr(VI)-induced kidney injury, at least in part, by regulating mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and the Nrf2 antioxidant signaling pathway.

Cuproptosis in atrazine-induced hepatotoxicity: ATOX1 as a therapeutic target for lycopene-mediated protection.

Lycopene regulates the JNK/p38MAPK signalling pathway and alleviates reproductive oxidative stress and apoptosis induced by heat stress in male rats

4-Nonylphenol (4-NP), an endocrine disruptor, is known to induce mutagenic, toxic, or carcinogenic effects, including testicular toxicity via inducing oxidative stress and apoptosis. The objective of this work was to determine the capacity of lycopene (LC) and gallic acid (GA) to protect testicular histological structure, biochemical responses, and semen parameters in rats exposed to 4-NP. In this 28-day dietary trial, six groups (n= 6 per group) received treatment via oral gavage: a control (corn oil, 2mL/kg/day), LC (10mg/kg body weight (BW)/day), GA (50mg/kg BW/day), 4-NP (125mg/kg BW/day), LC + 4-NP (LC followed by 4-NP), and GA + 4-NP (GA followed by 4-NP) groups. The results indicated that 4-NP administration adversely affects the final body weight, testicular histology, seminiferous epithelium heights (SEHs) (4-NP: 57.95 ± 0.49, p: 0.000), follicle-stimulating hormone (FSH) level, testis antioxidant capacity, testis malondialdehyde (MDA) level, and sperm viability and morphology. LC and GA supplementation significantly improved SEHs, activities of testis superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and sperm viability compared to the 4-NP group. Moreover, LC and GA exposures decreased histopathological lesions, including germinal epithelial degeneration, vacuolization, immature germ cells in the tubular lumen, and congestion in the interstitial area. Furthermore, they lowered TUNEL-positive cell counts and tubule percentages, testicular MDA levels, and abnormal sperm percentages. To our knowledge, this study provides one of the first systematic comparisons of lycopene and gallic acid in protecting against 4-NP-induced testicular toxicity under identical experimental conditions. The findings suggest that both compounds preserve testicular structure and function through their antioxidant and anti-apoptotic properties.

Enhancing antioxidant activity and bioaccessibility of lycopene and quercetin via synergistic co-delivery in gellan gum-stabilized oil-in-water emulsion.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a major and unavoidable environmental contaminant that poses serious risks to intestinal health. Lycopene (LYC), a natural carotenoid with potent antioxidant properties, has been reported to exert protective effects against oxidative stress. Phosphoglycerate mutase family member 5 (PGAM5) acts as a key signaling hub to control mitochondrial dynamics and mitophagy. This study aimed to elucidate the potential role of LYC in DON-induced intestinal damage and clarify the contribution of PGAM5. We established intestinal porcine epithelial cell models to explore the effects of DON and LYC on intestinal barrier integrity, mitochondrial function, mitophagy, and ferroptosis through assessments of cell viability, oxidative stress, iron accumulation, and autophagic activity. Mechanistic insights were validated using RNA sequencing, molecular docking, Western blotting, and immunofluorescence analyses. PGAM5 expression was modulated via plasmids and small interfering RNA. Our results demonstrated that DON disrupted barrier integrity, reduced cell motility, and induced cytoskeletal disorganization, accompanied by excessive mitophagy, lipid peroxidation, and ferrous iron accumulation, ultimately leading to ferroptosis. Notably, LYC alleviated DON-induced intestinal damage by inhibiting mitophagy and ferroptosis. Importantly, PGAM5 overexpression abolished the protective effects of LYC, indicating that PGAM5-mediated mitophagy-dependent ferroptosis plays a critical role in DON-induced intestinal damage. These findings suggest that LYC may serve as a potential therapeutic strategy for treating mycotoxin-induced intestinal disorders.

Soil salinization is one of the major challenges to agriculture, reducing productivity and directly affecting plant growth, germination, and physiology, especially in economically important crops such as Medicago sativa. Conventional soil management methods are not always sufficient to mitigate the adverse effects of salinity, highlighting the need for alternative and sustainable strategies. This study evaluated the phytoprotective potential of lycopene (LCP) against NaCl-induced stress in M. sativa. Seeds were treated with 256 µg/mL and 512 µg/mL of LCP combined with 50 mM NaCl and compared to a control group containing NaCl only. The combination of 256 µg/mL LCP with NaCl significantly increased germination, root and leaf growth, and reduced oxidative stress markers such as TBARS and iron content level, demonstrating a protective antioxidant effect. In contrast, the combination with 512 µg/mL LCP showed a lower protective effect, indicating that higher concentrations may induce additional oxidative stress. In silico molecular analysis revealed LCP affinity with the target protein (–5.062 kcal/mol), involving hydrogen bonds and hydrophobic interactions, suggesting stability and functional effects on the protein. The results demonstrate that LCP exerts a dose-dependent phytoprotective effect, especially when associated with NaCl, promoting resistance to salt stress and improving morphological and biochemical parameters in M. sativa. These findings indicate the potential of LCP as a promising natural compound to mitigate the adverse effects of salinity in agriculture.

Development and characterization of high internal phase emulsions for lycopene encapsulation with safflower seed meal globulin modified via ultrasound, heating and pH-shifting

Adding lycopene to the freezing media enhances the quality, antioxidant capacity, and fertilization ability of frozen-thawed Oure-type Tibetan sheep (Ovis aries) sperm.

Heat stress (HS) severely impairs boar reproductive function by inducing oxidative stress and inflammatory responses, while lycopene (LYC), as a potent antioxidant, exerts a potential protective effect on the male reproductive system. This study aimed to clarify the mechanism underlying LYC-mediated alleviation of HS-induced decline in semen quality in Rongchang boars, identify the most affected tissues, and explore its regulatory role in the Nrf2 (Nuclear factor E2-related factor 2) pathway. A total of 18 Rongchang boars with an initial body weight of 15.81 ± 1.07 kg were randomly assigned to three groups (6 boars per group): the control group (CON, 26 ± 1 °C), the heat stress group (HS, exposed to 35 ± 1 °C for 8 h daily), and the heat stress + 100 mg/kg lycopene group (HS + LYC). After 28 days of adaptive feeding and 14 days of HS treatment, samples were collected for semen quality analysis, testicular histological analysis, antioxidant index detection, transcriptome analysis, Nrf2 pathway detection, and inflammatory index detection. The results showed that HS significantly increased the sperm abnormality rate (p < 0.05), damaged the testicular structure, and induced oxidative stress in serum, lung, liver, left ventricle, testis, and epididymis (caput epididymis, corpus epididymis, cauda epididymis), with varying degrees of oxidative stress observed in these samples. Among these tissues, the testis and cauda epididymis exhibited the most significant responses to HS and LYC, with the comprehensive impact magnitudes of 317% and 514%, respectively. Enrichment analysis of differentially expressed genes (DEGs) in these two tissues revealed that the pathways mediating oxidative stress response displayed distinct tissue specificity, and all of them were closely associated with the Nrf2 antioxidant signaling pathway. HS significantly downregulated the mRNA expressions of Nrf2, Quinone Oxidoreductase (NQO1), Heme Oxygenase 1 (HMOX1) and Glutamate-Cysteine Ligase Catalytic Subunit (GCLC) genes as well as the protein level of Nrf2 in the testis and cauda epididymis, increased the protein level of Keap1, and significantly elevated the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in these two tissues (p < 0.05). Compared with the HS group, dietary supplementation of LYC significantly improved sperm motility and the proportion of rapidly progressive sperm, reduced the proportion of immotile sperm and sperm abnormality rate (p < 0.05), alleviated testicular damage and oxidative stress in various tissues, upregulated the mRNA expressions of Nrf2 and HMOX1 genes in the testis as well as the mRNA expressions of Nrf2, NQO1, HMOX1 and GCLC genes in cauda epididymis (p < 0.05), significantly increased the Nrf2 protein level and decreased the Keap1 protein level in these two tissues, and simultaneously decreased the levels of the aforementioned inflammatory factors (p < 0.05). In conclusion, dietary supplementation with 100 mg/kg LYC can alleviate HS-induced decline in semen quality and testicular damage by regulating the oxidative status and inflammatory level of relevant tissues (e.g., testis and cauda epididymis) in boars, and this protective effect may be associated with the regulation of the Nrf2 signaling pathway.

Guava is a superfruit with a high amount of nutrients and phytochemical compounds. The colored guava is known for its nutritional value, as it is rich in antioxidants and reduces the risk of certain chronic diseases. Thus, the current study was conducted at the ICAR‐Indian Indian Institute of Horticultural Research, Bengaluru, to assess the variability in quality, phytochemicals, and color traits in intervarietal progenies (“Purple local × Arka Poorna”) of guava. A wide range of variability for all the quality and phytochemical traits likes fruit weight (FW), outer pulp thickness (OPT), pulp per cent (PP), seed hardiness (SH), total soluble solids (TSS), titratable acidity (TA), vitamin C (VIT‐C), total carotenoids (TC), lycopene (LY), total anthocyanins (TAC), total flavonoids (TF), total antioxidants (TAA), and total phenols (TP) along with peel and pulp color was observed in intervarietal progenies. The coefficient of variation values for quality traits ranged from 0.67% to 89.79%. The cluster analysis grouped all the colored pulp with higher FW, OPT, PP, and high phytochemical traits progenies in cluster IV and II, respectively. The principal component analysis (PCA) explained 75.8% of total variance for all the traits studied in the intervarietal progenies. The colored (pulp/peel) progenies were found to be superior for all the quality traits evaluated and meeting the consumer demand for high nutritional value. Hence, the identified superior colored (pulp/peel) progenies namely PLAP8‐28, PLAP9‐13, PLAP11‐1, PLAP11‐19, PLAP11‐24, PLAP13‐20, PLAP8‐20, and PLAP8‐24 could be exploited in the crop improvement program.

Sulfamethoxazole (SMZ), a sulfonamide antibiotic widely used in aquaculture, and its metabolites are released into the environment, becoming a potential threat to the health of hydrobionts. Lycopene (LYC), a potent antioxidant, was studied and found to possess anti-inflammatory and anti-oxidative stress pharmacological activities. This study aims to explore the potential protective effect of LYC on SMZ-induced gill injury in grass carp and its mechanism. The grass carp were exposed to 0.3μg/L SMZ and 10mg/kg body weight of LYC for 30days. Fish gills were collected for examination of microstructure, oxidative stress indicators, and expression of related proteins. Our study found that SMZ exposure caused oxidative stress in fish gill tissues, with microstructural alterations. Meanwhile, relevant indicators of inflammation, such as IL-1β and NF-κB, were significantly up-regulated compared with the Con group, creating an inflammatory environment in vivo. In addition, SMZ also activated ER stress-related proteins and autophagy marker proteins. The above toxic effects were significantly alleviated after LYC intervention, and the mechanism involved LYC activating the Nrf2 pathway by binding to Keap1, upregulating HO-1 and NQO1 to enhance antioxidant capacity, and inhibiting NF-κB-induced inflammatory response. In conclusion, our study demonstrated that LYC as a dietary supplement could alleviate SMZ-induced damage in fish gills, and this natural antioxidant is expected to be developed into an effective drug to reduce the harm caused by SMZ in aquaculture.