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Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2–associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.

Fenugreek seed (FS) contains abundant functional biomolecules that activate the antioxidative and immunity system of aquatic animals. In this study, the methanolic extract of FS was included in Nile tilapia diets at 0, 0.05, 0.1, 0.15, and 0.2% levels and fed to fish for 90 days. Nile tilapia (10.57 ± 0.14 g) were randomly divided into five triplicate groups to check the growth performance, haematobiochemical profile, immunity, antioxidative response, and tolerance to Aeromonas hydrophila infection. The results revealed that the methanolic extract of FS significantly improved the growth performance while reducing the feed conversion ratio (FCR). Methanolic extract of FS also modulated the haematobiochemical profile. Markedly, the lysozyme and phagocytic activities were activated by the dietary methanolic extract of FS. The superoxide dismutase (SOD) activity was improved, while the malondialdehyde (MDA) level was decreased by the dietary methanolic extract of FS. The SOD was markedly increased in the fish-fed dietary methanolic extract of FS at 0.1, 0.15, and 0.2%, while the MDA decreased in the fish fed 0.15 and 0.2%. The transcription of IL-1β, TNF-α, and TGF-β genes showed upregulated expression by ethanolic extract of FS. Accordingly, Nile tilapia showed high resistance against the A. hydrophila infection. The regression analysis revealed that the inclusion of 0.09% is recommended to improve the specific growth rate and FCR. In conclusion, the study revealed that an ethanolic extract of FS is recommended to enhance the growth performance, immunity, antioxidative response, and tolerance to A. hydrophila in Nile tilapia.

Nile tilapia Juveniles (19.50 ± 0.5 g) were fed on a basal diet (control group (CTR)) and a diet supplemented with 1 g Aspergillus oryzae (ASP) per kg diet for 12 weeks. Fish were then subjected to different salinity levels (0, 10, 15, and 20 practical salinity units (psu)) for another 15 days. Two-way ANOVA analysis revealed that the individual effects of ASP in Nile tilapia exposed to salinity levels presented a significant decrease (p < 0.05) in values of haemato-biochemical indices (such as glucose, cortisol, alanine transaminase, aspartate transaminase, and malondialdehyde) compared to those in the CTR group exposed to the same salinity levels. Moreover, significant increases (p < 0.05) of blood protein profile (albumin, globulin, and total protein), non-specific immune responses (lysozyme activity, phagocytic activity, and phagocytic index), and antioxidant enzymes activities (glutathione peroxidase, catalase, and superoxide dismutase) were observed in ASP-supplemented groups. Interestingly, there was significant (p < 0.05) downregulation of the mRNA expression values of heat shock protein 70 and interferon-gamma genes, alongside upregulation of the mRNA expression values of interleukin 1 beta and interleukin 8 genes, in the hepatic tissues of Nile tilapia in ASP-supplemented groups exposed to different salinities compared to those in the CTR group exposed to the same salinity levels. Taken together, these findings supported the potential efficacy of dietary supplementation with ASP in alleviating salinity stress-induced haemato-biochemical alterations, immune suppression, and oxidative stress in the exposed Nile tilapia.

Loss of normal function is an inevitable effect of aging. Several factors contribute to the aging process, including cellular senescence and oxidative stress.BackgroundLoss of normal function is an inevitable effect of aging. Several factors contribute to the aging process, including cellular senescence and oxidative stress.We investigate how Arthrospira platensis Nanoparticles (NSP) protect against aging injury induced by d-galactose (D-gal) in the rat. So, we subcutaneously (S/C) injected D-gal at 200 mg/kg BW to see if Arthrospira platensis Nanoparticles (NSP) might protect against the oxidative changes generated by D-gal. NSP (0.5 mg/kg body weight once daily by gastric gavage) was given to all groups apart from the control and D-gal groups. The d-gal + NSP group was supplemented with 200 mg of D-gal per kg BW once a day and NSP 0.5 mg/kg BW given orally for 45 days. Biochemical, mRNA expression, and histological investigations of brain tissues were used to evaluate the oxidative alterations caused by d-gal and the protective role of NSP.MethodsWe investigate how Arthrospira platensis Nanoparticles (NSP) protect against aging injury induced by d-galactose (D-gal) in the rat. So, we subcutaneously (S/C) injected D-gal at 200 mg/kg BW to see if Arthrospira platensis Nanoparticles (NSP) might protect against the oxidative changes generated by D-gal. NSP (0.5 mg/kg body weight once daily by gastric gavage) was given to all groups apart from the control and D-gal groups. The d-gal + NSP group was supplemented with 200 mg of D-gal per kg BW once a day and NSP 0.5 mg/kg BW given orally for 45 days. Biochemical, mRNA expression, and histological investigations of brain tissues were used to evaluate the oxidative alterations caused by d-gal and the protective role of NSP.Our data demonstrated that d-gal was causing significant reductions in relative brain and body weight with increased malondialdehyde (MDA) and redox oxygen species (ROS) levels and increases in serum creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme BB (CPK-BB) with marked decreases in the level of antioxidant enzyme activity in the brain and acetylcholinesterase activity augmented with a phosphorylated H2A histone family member X (γ-H2AX) level increased. The D-gal group had considerably higher phosphorylated p38 mitogen-activated protein kinases (P38MAPK) and C-Jun N-terminal (JNK) kinases. The d-gal administration stimulates the apoptotic gene expression by downregulating the brain superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid 2-related factor 2 (Nrf2). The NSP administration saved these parameters in the direction of the control. The brain histopathologic and immunohistochemistry analysis findings support our findings on NSP's protective role.ResultsOur data demonstrated that d-gal was causing significant reductions in relative brain and body weight with increased malondialdehyde (MDA) and redox oxygen species (ROS) levels and increases in serum creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme BB (CPK-BB) with marked decreases in the level of antioxidant enzyme activity in the brain and acetylcholinesterase activity augmented with a phosphorylated H2A histone family member X (γ-H2AX) level increased. The D-gal group had considerably higher phosphorylated p38 mitogen-activated protein kinases (P38MAPK) and C-Jun N-terminal (JNK) kinases. The d-gal administration stimulates the apoptotic gene expression by downregulating the brain superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid 2-related factor 2 (Nrf2). The NSP administration saved these parameters in the direction of the control. The brain histopathologic and immunohistochemistry analysis findings support our findings on NSP's protective role.The NSP may be a promising natural protective compound that can prevent aging and preserve health.ConclusionThe NSP may be a promising natural protective compound that can prevent aging and preserve health.

Decreased stemness and increased cellular senescence impair the ability of mesenchymal stem cells (MSCs) to renew themselves, change into different cell types, and contribute to regenerative medicine. There is an urgent need to discover new compounds that can boost MSCs’ stemness and delay senescence. Therefore, this study aimed to investigate the impact of walnut kernel oil (WKO) and defatted (WKD) extracts on bone marrow (BM)-MSC stemness and senescence. Premature senescence and inflammation were induced in BM-MSCs using H2O2 and LPS, respectively. Phytochemical constituents of WKO and WKD extracts were detected by HPLC. The stemness (proliferation and migration), senescence-related markers (p53, p21, SIRT1, and AMPK), oxidative stress/antioxidant markers, inflammatory cytokines, and cell cycle of BM-MSCs were measured by MTT assay, qPCR, ELISA, and flow cytometry. WKO and WKD extracts improved rat BM-MSC stemness, as evidenced by (1) increased cell viability, (2) decreased apoptosis (low levels of Bax and caspase3 and high levels of Bcl2), (3) upregulated MMP9 and downregulated TIMP1 expression, and (4) cell cycle arrest in the G0/G1 phase and declined cell number in the S and G2/M phases. Additionally, WKO and WKD extracts reduced rat BM-MSC senescence, as indicated by (1) decreased p53 and p21 expression, (2) upregulated expression and levels of SIRT1 and AMPK, (3) reduced levels of ROS and improved antioxidant activity (higher activity of CAT, SOD, and GPx and upregulated expression of NrF2 and HO-1), and (4) declined levels of TNFα, IL1β, and NF-κB. When compared to the WKO extract, the WKD extract had a greater impact on the induction of stemness and reduction of senescence of BM-MSCs due to its stronger antioxidant activity, which could be attributed to its higher levels of flavonoids and phenolic compounds, as detected by HPLC analysis. WKO and WKD extracts enhance rat BM-MSC stemness and protect them from senescence, suggesting their potential use as enhancers to increase MSCs’ therapeutic efficacy.

This research investigates the effects of dietary supplementation with Ecobiol plus ® (Bacillus amyloliquefaciens CECT5940) on the growth performance, physiological responses, oxidative stress, and immune status of Nile tilapia (Oreochromis niloticus) fingerlings revealed to Aeromonas hydrophila . A total of 525 Nile tilapia fingerlings, averaging 30.00 ± 5.00 g in initial weight, were randomly divided into four groups (control and three experimental groups), each with three replicates of 25 fish. Ecobiol plus ® was integrated in the diet at concentrations of 0.0 (control), 0.1, 0.2, and 0.4 g/kg feed. Fish were fed at 3% of their biomass daily, with biweekly adjustments based on growth. The feeding trial lasted 8 weeks, followed by a 15-day challenge with Aeromonas hydrophila to evaluate immune responses and survival outcomes. The group receiving 0.4 g/kg of Ecobiol plus ® exhibited the most significant improvements in growth performance, including higher weight gain, specific growth rate, and feed conversion efficiency ( p  < 0.05). Blood and biochemical assessments indicated increased hemoglobin, total protein, and globulin levels, reflecting improved physiological and immunological conditions. Additionally, lysozyme activity and phagocytic response were markedly enhanced, demonstrating the probiotic’s immune-boosting potential. Histopathological evaluations revealed reduced gut, gills, and hepatopancreas lesions, especially in groups with higher supplementation levels. Fish in Group T4, fed with 0.4 g/kg Ecobiol plus ® , achieved the best growth performance, with a final weight of 77.96 ± 5.53 g, a weight gain of 42.46 ± 3.18 g, and a specific growth rate (SGR) of 1.51%/day, compared to the control group (T1) with a final weight of 75.26 ± 3.87 g, weight gain of 35.76 ± 2.08 g, and SGR of 1.24%/day. Survival rates considerably increased in the treated groups, with T4 exhibiting the highest rate of 96.00%, followed by T2 (94.68%), T3 (92.00%), and T1 (81.32%). Additionally, the LD50 of A. hydrophila was determined to be 3 × 10⁷ CFU/mL, underscoring the protective effect of Ecobiol plus ® in enhancing fish immunity and resilience against bacterial challenges. These results suggest that Ecobiol plus ® can be a natural, antibiotic-free additive to strengthen growth and disease resistance in Nile tilapia. The optimal inclusion level of Ecobiol plus ® is 0.4 g/kg for maximum benefit.

The impacts of oregano essential oil and sodium butyrate on the growth performance, hematological, biochemical, immunological, antioxidative, and gene expression profiles of Nile tilapia ( Oreochromis niloticus ) fingerlings were examined in this study. One hundred eighty healthy fingerlings (16.00 ± 2.00 g) were acclimated and accidentally divided into three groups, each further split into three replicates. The groups were fed a basal diet (control) or diets supplemented with 0.5% and 1% oregano essential oil and sodium butyrate for eight weeks (The feed additives were administered continuously throughout an 8-week trial period, simulating a practical feeding strategy that would be feasible during high-risk periods (e.g., post-handling stress, seasonal disease outbreaks). Fish fed the supplemented diets demonstrated significantly greater growth performance, with the oregano 1% + sodium butyrate 1% group achieving the highest final body weight (36.91 ± 0.66 g) and lowest feed conversion ratio (1.32 ± 0.04). Hematological indices, including RBC count, Hb, and PCV, were substantially improved. Biochemical analysis revealed reduced ALT, AST, urea, and creatinine levels alongside elevated total protein and globulin concentrations in treated groups. Immunological and antioxidative parameters, such as WBC count, phagocytic activity, SOD, and GPX, showed significant enhancements, particularly in the oregano 1% + sodium butyrate 1% group. Gene expression analysis exposed upregulation of immune-related (TNF-α, IL-1β) and antioxidative (SOD, GPX) genes in supplemented groups, highlighting their role in enhancing health and stress responses. Post Aeromonas hydrophila infection, the supplemented groups exhibited improved immunity, antioxidative status, and survival. These findings suggest that dietary supplementation with oregano essential oil and sodium butyrate, particularly at 1% inclusion, effectively enhances growth, health status, immunity, and gene expression in Nile tilapia.

Abstract Zinc is an essential element for metabolism of Nile tilapia (Oreochromis niloticus). Nanomaterials have important benefits in aquaculture. The present study evaluated the effects of green-synthesized zinc oxide nanoparticles (ZnO-NPs) using Ulva fasciata extract as an anti-fungal agent against Candida albicans (C. albicans) in vitro and in vivo in O. niloticus. A total of 252 apparent healthy O. niloticus (20 ± 0.457 g/fish) were randomly allocated into six groups: The 1st group fed on basal diet contaminated with C. albicans 15 × l06 CFU/g diet, the 2nd group fed basal diet only, the 3rd and 5th groups fed the basal diet supplemented with 40 or 60 mg/kg ZnO-NPs, respectively, and the 4th and 6th groups fed the basal diet contaminated with C. albicans 15 × l06 CFU/g and concomitantly supplemented with 40 or 60 mg/kg ZnO-NPs, respectively. The experiment lasted for 8 weeks. The phyco-synthesized ZnO-NPs were characterized by XRD, UV-V, FTIR, TEM, and zeta potential. The anti-fungal activities of ZnO-NPs and the morphological changes to C. albicans cell due to ZnO-NPs were detected. The results revealed that dietary supplementation with the green-synthesized ZnO-NPs significantly improved the growth performance, survival, serum lysozyme activity, phagocytic activity, phagocytic index, respiratory burst activity, expression of immune-related genes (IL-1β, TGF, TNF-α), digestive enzyme activity, and histopathological finding in C. albicans-infected group, with a relative superiority to 40 mg/kg feed ZnO-NPs. It could be concluded that supplementing diets with 40 mg/kg of phyco-synthesized ZnO-NPs could be considered a better choice for controlling candidiasis in Nile tilapia.

Background/Objectives: The present study aimed to evaluate the nephroprotective role of Khellin (Khe) against cisplatin (CDDP)-mediated nephrotoxicity in rats. Methods: We assessed oxidative stress markers (MDA, CAT, SOD, GPx, and iNOs), inflammatory markers (TNFα, IL6, IL10, and MCP1), apoptotic markers (Bax and Bcl2), and the renal damage marker (Kim1). Network pharmacology and molecular docking studies were performed. In vitro, Khe effects were tested on normal kidney cells (Vero) and liver cancer cells (HepG2) treated with CDDP. Results: Network pharmacology and docking suggested Khe’s activity primarily affects oxidative stress and inflammatory pathways, notably through MAPK14 and PI3K downregulation. In vitro, Khe reduced CDDP’s cytotoxicity in Vero cells while maintaining anti-proliferative effects on HepG2 cells. In vivo, CDDP significantly increased serum creatinine, urea, Kim1, oxidative stress markers (MDA and iNOS), and inflammatory markers (TNFα, IL6, and MCP1) while decreasing antioxidant markers (SOD, GPx, CAT, and SOD3) and anti-inflammatory cytokine (IL10) levels. Khe treatment dose-dependently attenuated these changes, with the 100 mg/kg dose showing the most significant renoprotection. Histopathological analysis confirmed improved renal tissue integrity in Khe-treated groups. Conclusions: This study demonstrates that Khe exerts significant nephroprotective effects against CDDP-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis while improving renal function and structure. These findings suggest Khe as a promising therapeutic candidate for preventing CDDP-related kidney injury.

Aeromonas hydrophila infection is one of the major diseases that cause inflammation and immunodepression in aquatic animals. Likewise, waterborne toxins are known for their negative impact on the immunity and antioxidant responses of aquatic organisms. In this study, Lactobacillus plantarum (LP20) was incorporated in Nile tilapia, Oreochromis niloticus , diets (50 mg/kg) to investigate its role in the antioxidant capacity, immunity, and anti-inflammation induced by deltamethrin (DLM) toxicity (96-h LC 50 was 14.9 μg/L) and A. hydrophila (LD 50 , 2 × 10 8 CFU/ml). One hundred and twenty healthy fish with an initial weight of 28.21 ± 1.34 g were allotted in 12 glass aquaria (60 L) and divided randomly into four groups (triplicates, 10 fish per aquarium). The control fish neither received LP20 nor were exposed to DLM. The second group of fish was fed the control diet and subjected to DLM (DLM group). The third group of fish was provided with LP20 without DLM toxicity (LP20 group), and the fourth group of fish was fed LP20 and subjected to DLM (DLM + LP20 group). After 30 days, fish were intraperitoneally injected with A. hydrophila . Ten days post infection, the survival rate was lower in fish exposed to DLM than those exposed to LP20. Further, fish fed on LP20 had elevated serum total protein (sTP), albumin (ALB), globulin (GLB), phagocytic index (PI), phagocytic (PA), and lysozyme activities (LZM), but they had lower urea, uric acid bilirubin, creatinine, glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) activities after 24 h, 48 h, and 1 week post A. hydrophila challenge. However, fish exposed to DLM had lower sTP, ALB, GLB and higher urea, uric acid, bilirubin, creatinine, glucose, ALT, AST, and ALP after 24 h, 48 h, and 1 week post A. hydrophila challenge. Markedly, after the A. hydrophila challenge, fish exposed to DLM + LP20 displayed upregulated levels of superoxide dismutase ( SOD ), catalase ( CAT ), and glutathione peroxidase ( GPx ) genes. The transcription of interferon gamma ( IFN- γ), interleukin 12 ( IL-12 ), and tumor necrosis factor alpha ( TNF- α) was upregulated in DLM and DLM + LP20 groups. Fish exposed to DLM downregulated interleukin 8 ( IL-8 ) gene expression after A. hydrophila challenge. Further, fish displayed upregulation of heat shock protein 70 ( HSP70 ) gene expression after DLM toxicity. Besides, fish exposed to DLM toxicity and A. hydrophila infection had severe inflammatory features in the liver, spleen, gills, and intestine, while dietary LP20 relieved the inflammatory features. In summary, dietary LP20 relieves Nile tilapia from oxidative stress, immunosuppression, and inflammation induced by DLM and A. hydrophila infection.