Hamada S. Salem

Chlorfenapyr (CFP) is a widely used pesticide associated with nephrotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. This study investigated the protective effects of limonene (LM) and its nano-liposomal formulation (LM-LNPs) against CFP-induced renal injury in rats. Animals were divided into six groups—control, LM, LM-LNPs, CFP, CFP + LM, and CFP + LM-LNPs—and treated orally for 30 days. CFP exposure resulted in marked renal dysfunction, histopathological and ultrastructural damage, suppression of the NRF2/HO-1/NQO1 antioxidant pathway, depletion of endogenous antioxidants excessive generation of reactive oxygen and nitrogen species, lipid peroxidation products, and DNA damage. These changes were accompanied by activation of NF-κB/COX-2-mediated inflammation, mitochondrial respiratory impairment, disrupted energy metabolism, and induction of apoptosis. Co-treatment with LM significantly ameliorated these alterations, whereas LM-LNPs produced greater improvements in renal function, tissue architecture, redox homeostasis, mitochondrial function, and inflammatory and apoptotic signaling. Immunohistochemical analyses further confirmed enhanced NRF2 expression and reduced NF-κB immunoreactivity in LM-LNP-treated kidneys. Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.

Background/Objectives: Nickel exposure is a significant environmental and occupational risk factor associated with the onset and progression of chronic liver diseases due to its capacity to induce persistent oxidative stress, inflammation, and hepatocellular injury. This study aimed to evaluate the enhanced hepatoprotective and antioxidant/anti-inflammatory effects of naringin-loaded nanoliposomes (NRG-NLPs), a novel nanoformulation designed to improve the bioavailability of naringin, a citrus-derived flavonoid phytochemical, against nickel sulfate (NiSO₄)-induced hepatotoxicity in male Wistar rats. Methods: Ninety rats were allocated into six groups (n = 15 each): control, NRG, NRG-NLPs, NiSO₄, NiSO₄ + NRG, and NiSO₄ + NRG-NLPs. Treatments consisted of oral administration of NRG or NRG-NLPs (80 mg/kg/day) and intraperitoneal injections of NiSO₄ (20 mg/kg/day) for three weeks. Endpoints included assessment of growth performance, serum biochemistry, hepatic antioxidant status, inflammatory mediators, apoptotic gene expression, nickel tissue accumulation, and histopathological and ultrastructural liver changes. Results: NiSO₄ exposure induced marked hepatic injury, evidenced by reduced body weight, adverse serum biochemical profiles, increased hepatic enzymes and bilirubin, elevated oxidative damage markers (MDA, protein carbonyls), increased proinflammatory cytokines, and upregulation of HMGB1, PI3K, mTOR, JAK/STAT, and proapoptotic genes, accompanied by aberrant nickel accumulation and severe histopathological alterations. Co-treatment with NRG-NLPs significantly ameliorated biochemical and histological disturbances, restored antioxidant defense systems (SOD, CAT, GPx, GSH, Nrf2, HO-1), and modulated key pathways of inflammation (NF-κB, TNF-α, IL-6), fibrosis (TGF-β), cell survival, and apoptosis more effectively than crude naringin. NRG-NLPs also substantially reduced hepatic nickel deposition and preserved near-normal liver architecture. Conclusions: These findings demonstrate that nanoformulated naringin confers superior hepatoprotective benefits against nickel-induced liver injury through enhanced bioavailability and multi-pathway modulation, supporting its translational potential as a citrus-derived medicinal phytochemical and dietary bioactive for the prevention and therapeutic intervention of oxidative and inflammatory chronic liver disease.

Fish and their ectoparasites serve as model organisms for evaluating aquatic ecosystem health and can thus function as bioindicators of environmental pollution. This study, therefore, investigates the gene expression of biomarkers of effect in Clarias gariepinus inhabiting a polluted drain called the Kitchener Drain and the Nile River (a reference habitat). Ectoparasites and metacercariae of digenean endoparasites on the collected fish were examined to further clarify the impact of pollution. Compared with the Nile River, the Kitchener Drain contained significantly elevated concentrations of heavy metals, bicarbonates, sulfates, and minerals. Interestingly, the prevalence, mean intensity, and abundance of ectoparasitic monogeneans from C. gariepinus collected from the Nile River were higher compared with those from the Kitchener Drain, whereas the drain had higher levels of metacercaria of the digenean endoparasite Centrocestus formosanus. Fish from the Kitchener Drain had significantly elevated hepatic expressions of genes related to metal toxicity, oxidative stress, inflammation, heat shock response, and xenobiotic metabolism. The results indicate that C. gariepinus exposed to metals and other pollutants triggers an adaptive response involving multiple stress-response pathways. The findings also highlight the impact of pollution on parasitic infestation in this fish population. The study supports the utilization of molecular biomarkers and ectoparasitic infestation as early warning signals for water pollution.

Kidney diseases are a significant global health issue, often progressing to life-threatening conditions. Diethylnitrosamine (DENA), a well-recognized environmental carcinogen, elicits renal toxicity primarily through mechanisms involving oxidative stress and inflammation. This research evaluated the prophylactic effects of graviola (Annona muricata L.) leaves extract in preventing renal toxicity and oxidative stress caused by DENA in male rats. The experimental design consisted of four distinct groups: Control, Graviola, DENA, and DENA plus Graviola. Renal function biomarkers, oxidative stress indicators, free radical parameters, and inflammatory and apoptotic markers were assessed. DENA administration significantly elevated serum concentrations of urea, creatinine, and uric acid, as well as malondialdehyde, whereas significantly reducing the total protein content and concentrations of antioxidant markers such as glutathione, superoxide dismutase, catalase, glutathione peroxidase, and total antioxidant capacity. It also significantly elevated inflammatory mediators (IL-6, TNF-α, IL-1β, and CRP) and apoptotic markers (annexin V, caspase 3, and P53) but lowered the anti-apoptotic protein BCL2. Co-administration of graviola extract significantly reversed these pathological changes by normalizing renal function markers, strengthening antioxidant defenses, and mitigating inflammation and apoptotic indicators. The findings suggest that graviola protects against DENA toxicity by reducing oxidative stress, boosting antioxidants, and suppressing inflammation and apoptosis. Graviola may emerge as a promising therapeutic candidate for preventing renal injury associated with environmental toxins like DENA.

The invasion of fish by heavy metals is a recognized environmental problem. Heavy metals, after leaking into the water, penetrate fish directly through the gill and later the skin. Fish develops protective defense mechanisms against the damaging effects of heavy metals. This study was aimed to investigate the concentrations of certain metals (cadmium, iron, manganese, cobalt, and lead) in the muscle tissues of the Nile tilapia (Oreochromis niloticus) and their possible impact on its histological, nanomechanical, and biochemical biomarkers. The results showed that fish muscle from the polluted site contained high levels of heavy metals compared to the reference site. Biochemical profile of the Nile tilapia showed that serum glucose, total proteins, uric acid, creatinine, bilirubin, superoxide dismutase, and malondialdehyde were elevated in exposed tilapia compared to their corresponding reference. Histological examination of the liver showed severe alterations in the liver tissue. Nanomechanical properties (roughness and stiffness) confirmed the damaging effect of metals on the liver tissue. These findings provide a rational application of histological, nanomechanical and biochemical parameters to be used as indicators of metal stress. Integrated biomarker response is a comprehensive index of all biomarkers and a good indicator of the health status of aquatic ecosystem.

Chemical pollution poses adverse effects on aquatic organisms, including altered gene expression. This study, therefore, investigated the hepatic expression of biomarkers of exposure and effect in Oreochromis niloticus inhabiting the drainage canal of a sugarbeet factory (an industrially polluted habitat) and the Nile River (a reference habitat). Compared to the Nile River, the drainage canal contained significantly elevated levels of heavy metals (Cd, Fe, Mn, Co, and Pb), nitrate, ammonia, nitrite, chemical oxygen demand, and biological oxygen demand. The liver of O. niloticus from the drainage canal accumulated significantly higher concentrations of the heavy metals. O. niloticus from the drainage canal had significantly higher hepatic expressions of genes related to oxidative stress (GSTa, GPx, and NRF2), metal toxicity (MT), endocrine disruption (Vtg), and hypoxia (HIF1a) and a significantly lower hepatic expression of the apoptosis-associated CAS gene. CYP1A (a detoxification biomarker) expression did not exhibit significant differences. These results provide insights into complex adaptive responses of O. niloticus to multiple chemicals and support the utilization of molecular biomarkers as warning signals for water pollution.