Copper nanoparticles are widely utilized in a variety of applications, including metal catalysts, semiconductors, heat transfer fluids in machine tools, and even in antibacterial medications. Forty mature healthy Westar rats were utilized in the current investigation and grouped randomly into four groups (n = 10 rats/group). Group I (G1) was kept as a control group, but G2, G3, and G4 were intraperitoneally injected with CuO NPs with a dose (5 mg, 10 mg, 25 mg/kg body weight/day) respectively for 9 days. Rats were sacrificed; then, the livers and kidneys were dissected and subjected to histopathological and immunohistochemical examination. Our findings of G2 and G3 revealed mild to moderate degenerative changes within the hepatic parenchyma, moderate blood vessel congestions, glycogen depletion, hemosiderosis, and microvesicular steatosis (fatty changes within the hepatocytes). In addition, at the level of kidney, our examination clarified moderate degenerations of the renal corpuscles and renal tubules with moderate swelling and congestions of the glomerulus with moderate vacuolations in the renal tubules lining epithelium. On the other hand, increasing the dose of CuO NPs, the toxicity became more obvious, where the liver of G4 revealed severe necrosis of hepatocytes with completely disorganizations of the hepatic rays, loss of the hepatic architectures, severe steatosis, severe hemosiderosis, sinusoidal dilatations with congestions, as well as severe fibrous tissue proliferation with anti-inflammatory cell infiltrations specially around portal triad with hyperplasia of bile duct. Meanwhile in kidney, G4 clarified severe necrosis and atrophy of the renal corpuscles with severe damage of Bowman’s capsule leading to completely disorganization and loss of normal renal cortex architectures, severe congestion of the glomerulus, severe necrosis of the renal tubules with damage and sloughing for its lining epithelium, and severe hemorrhage between renal tubules. In addition, severe and diffuse caspase 3 immunoreactivity were observed within the hepatic and renal tissues of G4. The present investigation was concluded that the CuO NPs have a potential toxicological effect on the hepatic and renal tissues that may affect their functions.-->

The main purpose of our study was to examine the role of selenium nanoparticles (SeNPs) and/or bee venom (BV) in ameliorating diabetic cardiomyopathy (DCM) and nephropathy (DN) at the biochemical, histopathological and molecular levels. Fifty male albino rats were used in this experiment, divided into five groups: control, Streptozocin (STZ) diabetic, STZ-diabetic treated with SeNPs, STZ-diabetic treated with BV, and STZ-diabetic treated with SeNPs and BV. Biochemically, STZ injection resulted in a significant increase in serum glucose, BUN, creatinine, CRP, CK-MB, AST, LDH and cardiac troponins with a significant decrease in the serum insulin and albumin concentrations. Histopathologically, STZ injection resulted in diabetes, as revealed by glomerulonephritis, perivascular hemorrhage, inflammatory cell infiltrations and fibrosis, with widening of interstitial spaces of cardiomyocytes, loss of muscle cells continuity and some hyaline degeneration. At the molecular levels, the expression levels of miRNA 328, miRNA-21, TGFβ1, TGFβ1R, JAK1, STST-3, SMAD-1 and NFκβ genes were significantly up-regulated, whereas the expression levels of SMAD-7 were significantly down-regulated. It is concluded that SeNPs and/or BV administration ameliorates the deleterious effects resulting from STZ administration through improving the biochemical, histopathological and molecular effects, suggesting their protective role against the long-term diabetic complications of DCM and DN.

Background: Doxorubicin (DOX), an anthracycline antibiotic, is a powerful chemotherapeutic agent effective against multiple types of cancer, particularly lung, breast, bladder and hematologic neoplasia (lymphomas and leukemia). However, its therapeutic usage is restricted by its known cardiotoxicity, which is associated with the production of oxidative stress. Enhancing antioxidant capacity represents a promising approach to mitigate DOX-induced cardiotoxicity. Hesperidin (HES), a citrus bioflavonoid, possesses several pharmacological effects, such as anti-inflammatory and antioxidant characteristics. Aim: This study was designed to evaluate the cardiotoxicity of DOX and assess the possible cardioprotective role of HES. Methods: Groups of Wistar rats were either treated with doxorubicin (4 mg/kg. bw., once a week for 5 consecutive weeks, intraperitoneally) or received co-treatment with hesperidin (100 mg/kg. bw./day in distilled water, 5 days in a week for 5 consecutive weeks, administered orally). Heart and blood samples were obtained for histological, immunohistochemical, and biochemical assessments. Results: DOX administration resulted in severe cardiotoxicity, as evidenced by significant elevations in cardiac biomarkers, including Troponin I (CTnI), Creatine kinase (CK-Total), Creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and Aspartate aminotransferase (AST). DOX also elevated pro-inflammatory cytokines, such as Interferon γ (IFN-γ), Interleukin 1β (IL-1β), and Tumor necrosis factor α (TNF-α). Furthermore, DOX induced oxidative stress and substantially reduced the levels of antioxidant enzymes, including Glutathione peroxidase (GPX), Superoxide dismutase (SOD), and Catalase (CAT). Histopathologically, DOX caused severe Zenker's necrosis, cardiomyocyte disarray, sarcoplasmic vacuolizations, cardiomyocyte congestion, and inflammatory cell infiltration. Immunohistochemically, DOX exhibited extensive apoptosis, as indicated by strong positive immuno-localization against anti-caspase-3 antibody. In contrast, co-treatment with HES protected cardiac tissues against cardiotoxicity of DOX, as indicated by the amelioration of histological abnormalities and the normalization of biochemical values. Conclusion: We can conclude that DOX induces severe cardiotoxicity characterized by oxidative stress, inflammation, pathological alterations, and apoptosis. Co-treatment with HES demonstrates significant cardioprotective effects by virtue of its potent anti-inflammatory, antioxidant, cytoprotective, and antiapoptotic characteristics.

Background: Although, gold nanoparticles (GNPs) are attracting more and more attention due to their ease of synthesis, modification and great potential value in biomedical application, exhibited harmful effects on human health and other living species. Quercetin (Qur) clarify diverse pharmacological effects specially anti-inflammatory, antiapoptotic, and antioxidant ones. Aim: This study aimed to evaluate the probable nephrotoxicity induced by different diameters of sphere GNPs, as well as the nephroprotective role of Qur. Methods: A total of fifty-four healthy mature male albino rats were grouped and treated with or without sphere GNPs; 10, 20 & 50 nm and quercetin (200 mg/kg b.wt.). The effects of GNPs and Qur were estimated through the collections of blood and kidney samples from euthanized rats and performed to biochemical, histopathological, and immunohistochemical investigations. Results: In comparison between different diameters of GNPs, the 10 nm GNPs revealed more significant elevations in all renal function parameters; Creatinine, Urea, BUN and Uric acid followed by 20 nm then 50 nm. Pre-cotreatment with Qur decreased all renal functional values. Histopathologically, 10 nm revealed the most potent renal pathological changes that represented in renal cortex with cloudy swelling of renal tubules, hypercellularity of some glomeruli, severe congestion of renal blood vessels, focal inter tubular edema, and vascular endotheliosis (degeneration of endothelium). In addition, the renal medulla revealed perivascular inflammatory cellular infiltration, perivascular fibrosis, intra tubular glycogen deposition and casts deposition of mainly cellular casts. On the other hand, Qur treatment ameliorated most of these pathological changes. Conclusion: The size of GNPs is pivotal in their pathological effect on renal tissues where the small-sized GNPs; 10 nm has more potent cytotoxic, inflammatory, and apoptotic effects rather than the larger ones. Otherwise, Qur clarified a significant mitigating role against the nephrotoxicity of the GNPs.

OBJECTIVE: To evaluate the potential contribution of glycyrrhizin (GLZ) to mitigate the testicular toxicity linked to cisplatin (CIS) intoxication. METHODS: 40 mature male Wistar albino rats (Rattus norvegicus albinus) were randomly divided into 4 equal groups (n = 10) for 60 days: the control group, CIS-treated group (single dose of 7 mg/kg, IP), GLZ-treated group (25 mg/kg, PO), and GLZ plus CIS–treated group. Blood and testis samples were examined using biochemical, histological, and immunohistochemical techniques. Semen samples were also obtained, and any abnormalities were reported. RESULTS: Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were all markedly reduced by CIS. Oxidative stress and a significant reduction in levels of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase were linked to CIS. Immunohistochemically, CIS showed diffuse, significantly positive immunolocalizations against the anti-caspase 3 antibody, indicating widespread apoptosis within the testicular parenchyma. Histopathologically, CIS showed diffuse coagulative necrosis of spermatogenic cells, necrotic Sertoli cells, intertubular edema, and Leydig cell hyperplasia. Moreover, CIS revealed a noteworthy increase in sperm abnormalities. Pre-coadministration and posttreatment with GLZ mitigated the majority of these detrimental consequences, and serum levels of antioxidant enzymes, luteinizing hormone, follicle-stimulating hormone, and testosterone were significantly elevated. CONCLUSIONS: Glycyrrhizin has been proven to be a strong antioxidant as well as antiapoptotic and cytoprotective against CIS testicular damage. CLINICAL RELEVANCE: The described model is a tool to evaluate the testicular protective impact of GLZ.

Purpose: Gold nanoparticles (GNPs) as pharmaceutical and drug delivery tools exhibited harmful effects on human health and other living species. Quercetin reveals various pharmacological effects specially antioxidant, anti-inflammatory and antiapoptotic. This study is directed to investigate hepatotoxicity of GNPs, in addition, to assess the impact of quercetin in mitigating the toxicological effects of GNPs. Methods: Groups of rats were treated with or without sphere GNPs (10, 20 and 50 nm) and quercetin (200 mg/kg b.wt.). Blood and liver samples from euthanized rats were subjected to biochemical, hematological, histopathological, and immunohistochemical investigations. Results: In comparison with 20 and 50 nm treated groups, the 10 nm GNPs significantly increased serum hepatic enzymes; AST, ALT, ALP and bilirubin. These 10 nm GNPs were associated with oxidative stress and markedly decreased antioxidant enzymes: GPX, CAT and SOD. Immunohistochemically, 10 nm GNPs expressed intense positive signals in nuclei of hepatocytes when stained with anti-caspase-3 antibody confirming extensive apoptosis. Pre-cotreatment with quercetin decreased all tested hepatic enzymes and increased serum level of antioxidant enzymes compared to 10 nm GNPs. Quercetin treatment strongly exhibited anti-Ki67 antibody (proliferative marker) indicating high proliferation of hepatic parenchyma. Histopathologically, 10 nm GNPs revealed diffuse hydropic degenerations, severe sinusoidal congestion, coagulative necrosis, sever steatosis and diffuse hemosiderosis within the hepatic parenchyma. Quercetin treatment ameliorated most of these pathological effects. Conclusion: The smaller diameters of GNPs induce potential oxidative stress, cytotoxic, and apoptotic effects in hepatic tissues rather than larger ones. In addition, quercetin demonstrated a significant prophylactic role against hepatotoxicity of GNPs.