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Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti‐inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer‐407 (P‐407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P‐407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P‐407‐adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3‐hydroxy‐3‐methylglutaryl CoA (HMG‐CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low‐density lipoprotein receptor (LDL‐R) and ATP‐binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL‐R, and ABCA1, and suppressed HMG‐CoA reductase in P‐407‐administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro‐inflammatory mediators (interleukin [IL]‐6, IL‐1β, tumor necrosis factor [TNF]‐α, interferon‐γ, IL‐4 and IL‐18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto‐nucleoside triphosphate diphosphohydrolase (E‐NTPDase) and ecto‐adenosine deaminase (E‐ADA) as well as NO and TNF‐α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward LPL, HMG‐CoA reductase, LDL‐R, PSK9, ABCA1, and E‐NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E‐NTPDase and E‐ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a highly toxic commonly used pesticide and can seriously harm human health. This study assessed the potential of galangin (GAL), an antioxidant flavonoid, to attenuate oxidative stress, inflammation and kidney injury caused by CPF, emphasizing the role of farnesoid-x-receptor (FXR) and Nrf2. Rats were supplemented with CPF and GAL for 28 days. CPF increased serum creatinine, urea and Kim-1, provoked several tissue alterations, and increased kidney ROS, malondialdehyde (MDA), NF-κB p65, TNF-α, iNOS, and caspase-3. GAL effectively ameliorated serum kidney injury markers, ROS, MDA, and TNF-α, suppressed NF-κB p65, iNOS, and caspase-3, and enhanced antioxidants. GAL suppressed Keap1 and upregulated FXR, Nrf2, HO-1 and NQO-1 in CPF-administered rats. GAL exhibited binding affinity with Keap1, FXR, caspase-3, iNOS, HO-1, and NF-κB. In conclusion, GAL is effective in preventing CPF nephrotoxicity by attenuating oxidative stress and inflammation. This protection is linked to upregulation of antioxidants, Nrf2/HO-1 signaling and FXR. • Chlorpyrifos induces oxidative stress, NF-kB activation, and inflammation. • Galangin ameliorates chlorpyrifos nephrotoxicity and suppress inflammation. • Galangin activates Nrf2/HO-1 and fernesoid X receptor in rat kidney. • Galangin prevents chlorpyrifos-induced oxidative stress and apoptosis in rat kidneys. [ABSTRACT FROM AUTHOR]

Hyperuricemia represents a risk factor for the progression of chronic kidney disease. Oxidative stress and inflammation are implicated in the mechanisms underlying hyperuricemia-mediated kidney injury. Monolluma quadrangula possesses several beneficial effects; however, its effect on hyperuricemia has not been investigated. This study evaluated the renoprotective and xanthine oxidase (XO) inhibitory activity of M. quadrangula in hyperuricemic rats. Phytochemical investigation revealed the presence of six known flavonoid isolated for the first time from this species. The rats received M. quadrangula extract (MQE) and potassium oxonate (PO) for 7 days. In vitro assays showed the radical scavenging and XO inhibitory activities of MQE, and in silico molecular docking revealed the inhibitory activity of the isolated flavonoids towards XO. Hyperuricemic rats showed elevated serum uric acid, creatinine, urea, and XO activity, and renal pro-inflammatory cytokines, MDA and NO, and decreased GSH, SOD, and catalase. MQE ameliorated serum uric acid, urea, creatinine, and XO activity, and renal pro-inflammatory cytokines. In addition, MQE attenuated renal oxidative stress, enhanced antioxidants, downregulated URAT-1, and GLUT-9 and upregulated OAT-1 in PO-induced rats. In conclusion, M. quadrangula attenuated hyperuricemia and kidney impairment by suppressing XO activity, oxidative stress and inflammation, and modulating urate transporters. [ABSTRACT FROM AUTHOR]

Liver injury is among the adverse effects of the chemotherapeutic agent cyclophosphamide (CP). This study investigated the protective role of the flavone apigenin (API) against CP-induced liver damage, pointing to the involvement of Nrf2/HO-1 signaling. Rats were treated with API (20 and 40 mg/kg) for 15 days and received CP (150 mg/kg) on day 16. CP caused liver damage manifested by an elevation of transaminases, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and histological alterations, including granular vacuolation, mononuclear cell infiltration, and hydropic changes. Hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) were increased and glutathione (GSH) and antioxidant enzymes were decreased in CP-administered rats. CP upregulated the inflammatory markers NF-κB p65, TNF-α, IL-6, and iNOS, along with the pro-apoptotic Bax and caspase-3. Pre-treatment with API ameliorated circulating transaminases, ALP, and LDH, and prevented histopathological changes in CP-intoxicated rats. API suppressed ROS, MDA, NO, NF-κB p65, iNOS, inflammatory cytokines, oxidative DNA damage, Bax, and caspase-3 in CP-intoxicated rats. In addition, API enhanced hepatic antioxidants and Bcl-2 and boosted the Nrf2 and HO-1 mRNA abundance and protein. In conclusion, API is effective in preventing CP hepatotoxicity by attenuating oxidative stress, the inflammatory response, and apoptosis. The hepatoprotective efficacy of API was associated with the upregulation of Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia increases the risk of liver damage. Oxidative stress and aberrant inflammatory response are entangled in diabetes-associated liver injury. This study evaluated the protective effect of the flavonoid galangin (Gal) on glucose intolerance, liver injury, oxidative stress, inflammatory response, and Nrf2/HO-1 signaling in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats received Gal for six weeks. STZ-induced rats showed glucose intolerance, hypoinsulinemia, elevated glycated hemoglobin (HbA1c), and decreased liver glycogen. Gal ameliorated glucose intolerance, reduced HbA1c%, increased serum insulin and liver glycogen and hexokinase activity, and suppressed glycogen phosphorylase, glucose-6-phosphatase and fructose-1,6-biphosphatase in diabetic rats. Circulating transaminases, ALP and LDH, and liver ROS, MDA, TNF-α, IL-1β, and IL-6 were increased and GSH, SOD, and CAT were diminished in diabetic rats. In addition, diabetic rats exhibited multiple histopathological alterations and marked collagen deposition. Treatment with Gal mitigated liver injury, prevented histopathological alterations, decreased ROS, MDA, pro-inflammatory cytokines, Bax and caspase-3, and enhanced cellular antioxidants and Bcl-2. Gal downregulated hepatic Keap1 in diabetic rats and upregulated Nrf2 and HO-1 mRNA as well as HO-1 activity. Molecular modeling studies revealed the ability of Gal to bind to and inhibit NF-κB and Keap1, and also showed its binding pattern with HO-1. In conclusion, Gal ameliorates hyperglycemia, glucose intolerance, oxidative stress, inflammation, and apoptosis in diabetic rats. Gal improved carbohydrate metabolizing enzymes and upregulated Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

The therapeutic properties of tin nanoparticles have been proved in recent years. One of their probable effects is anti‐anemia. In this study, tin nanoparticles were synthesized and characterized in aqueous medium using Ziziphora clinopodioides Lam leaf aqueous extract as the reducing and stabilizing agent. We also assessed the antihemolytic anemia potential of tin nanoparticles (SnNPs) in an animal model of hemolytic anemia. Tin nanoparticles were characterized using many techniques including Fourier transform‐infrared and UV‐visible spectroscopy, X‐ray diffraction (XRD), energy dispersive X‐ray spectrometry, and field emission‐scanning electron microscopy (FE‐SEM). FE‐SEM images showed a uniform spherical morphology in size of 18.12 nm for the green synthesized nanoparticles. According to XRD analysis, SnNPs crystal size was17.94 nm. SnNPs had low cell viability dose‐dependently against human umbilical vein endothelial cell line. in vivo design, induction of hemolytic anemia was done by phenylhydrazine in 40 mice. Tin nanoparticles significantly (p ≤ 0.01) reduced the weight and volume of liver and spleen and the concentration of pro‐inflammatory cytokines, and increased the body weight, anti‐inflammatory cytokines concentration, total platelet, WBC, neutrophil, lymphocyte, eosinophil, monocyte, and basophil counts, and red blood cell parameters compared to the untreated mice. For the biochemical parameters, SnNPs significantly (p ≤ 0.01) increased the concentrations of GPx, CAT, and SOD in serum, liver, and spleen and decreased the concentration of GR in serum, liver, and spleen, and also erythropoietin, ferritin, and ferrous in serum as compared to the anemic mice. The 2,2‐diphenyl‐1‐picrylhydrazyl test showed similar antioxidant activities for SnNPs and butylated hydroxytoluene. The results demonstrate the excellent antihemolytic anemia, hematoprotective, cytotoxicity, and antioxidant potentials of SnNPs compared to other experimental groups. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a serious complication of diabetes and can lead to renal failure. Telmisartan (TEL) is an approved angiotensin II type 1 receptor blocker for the treatment of hypertension and possesses nephroprotective efficacy. The study investigated the beneficial effect of TEL on renal oxidative stress, inflammatory response, and apoptosis in type 1 diabetic rats, pointing to the possible role of Nrf2/HO-1 signaling. Diabetes was induced by streptozotocin (STZ), and TEL (5 and 10 mg/kg) was supplement for 8 weeks. TEL ameliorated hyperglycemia, prevented body weight loss and kidney hypertrophy, decreased serum creatinine and urea, and prevented histopathological alterations in diabetic rats. Malondialdehyde (MDA), nitric oxide (NO), NF-κB p65 and TNF-α were increased, whereas GSH, SOD and Bcl-2 were decreased in the kidney of diabetic rats. Treatment with TEL ameliorated oxidative stress, suppressed NF-κB p65 and TNF-α, and boosted cellular antioxidant defenses and Bcl-2. TEL upregulated Nrf2 and HO-1 in the kidney of both normal and diabetic rats. In addition, TEL downregulated VEGF and MMP-9 in the kidney of diabetic rats. In silico molecular docking simulations revealed the potent binding affinity of TEL to NF-κB, MMP-9, Keap1 and HO-1. In conclusion, TEL attenuates DN by ameliorating hyperglycemia, oxidative stress, inflammation, apoptosis and angiogenesis and upregulation of Nrf2/HO-1 signaling. • Telmisartan ameliorates hyperglycemia and kidney injury in diabetic rats. • Telmisartan attenuates renal oxidative stress and inflammation in diabetic rats. • Telmisartan upregulates renal Nrf2/HO-1 in diabetic rats. • Telmisartan downregulates renal VEGF and MMP-9 in diabetic rats. [ABSTRACT FROM AUTHOR]

Nephrotoxicity is a major complication that limits the therapeutic application of cisplatin (CIS). Oxidative stress and inflammation are implicated in CIS-induced acute kidney injury (AKI) and apoptotic cell death. Punicalagin (PUN), a polyphenol in pomegranate, possesses promising anti-inflammatory and antioxidant activities, and its beneficial effect against CIS-induced AKI has not been fully elucidated. This investigation evaluated the protective effect of PUN against CIS-induced renal oxidative stress, inflammation and cell death. Rats received PUN (25 and 50 mg/kg) for 10 days and a single injection of CIS at day 7. The results showed increased serum urea and creatinine and several histopathological alterations in the kidney of CIS-intoxicated rats. Renal malondialdehyde (MDA) and nitric oxide (NO) were increased, and reduced glutathione, superoxide dismutase and catalase were declined in rats treated with CIS. PUN effectively ameliorated kidney function and attenuated tissue injury induced by CIS, decreased MDA and NO, and enhanced antioxidant defenses. Additionally, PUN downregulated NF-κB p65, iNOS, TNF-α, IL-6 and IL-1β in the kidney of rats that received CIS. Bax and caspase-3 were increased, and Bcl-2 was decreased in the kidney of CIS-intoxicated rats, an effect that was reversed by PUN. PUN upregulated Nrf2 expression in the kidney of CIS-intoxicated rats. In conclusion, PUN prevents CIS-induced AKI in rats by attenuating oxidative stress, inflammatory response and apoptosis, and upregulating Nrf2 and antioxidants. [Display omitted] • Punicalagin prevented cisplatin nephrotoxicity in rats. • Punicalagin attenuated cisplatin-induced oxidative stress. • Punicalagin suppressed inflammation in kidney of cisplatin-treated rats. • Punicalagin mitigated apoptosis in kidney of cisplatin-treated rats. [ABSTRACT FROM AUTHOR]