Regulating ferroptosis by roflumilast attenuates cisplatin-induced kidney injury.

Acute kidney injury (AKI) represents a concerning health challenge that alters renal structure and function. Ferroptosis has been identified as a cell death mechanism involved in AKI. Cisplatin is a widely used antineoplastic agent, but AKI is a serious limitation to its clinical use.

Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy.

Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective treatment of severe diabetic retinopathy (DR) and macular edema, but a significant subset of people showed inadequate response to anti-VEGF intervention. Since elevation or overexpressing retinol binding protein 3 (RBP3) decreased risks for retinal pathologies and progression to severe DR, we compared the therapeutic profile of RBP3 and anti-VEGF to normalize retinal dysfunctions induced by diabetes. Intravitreous injection of recombinant human RBP3 (rhRBP3) and anti-VEGF antibodies (bevacizumab) inhibited retinal vascular permeability in Lewis rats induced by VEGF-A or after 2 months of diabetes induced by streptozotocin, in parallel with reductions of retinal VEGF and VEGFR2 expressions and tyrosine phosphorylation of VEGFR.

Inhibition of p75/p53 axis by ambrisentan suppresses apoptosis and oxidative stress-mediated renal damage in a cisplatin AKI model.

Cisplatin (CP) is a potent antineoplastic agent that triggers nephrotoxicity as a major adverse effect which can cause treatment interruptions and limitations to its clinical use. Nephrotoxicity associated with CP involves inflammation, oxidative stress, and apoptosis in kidney tubules. The objective of this work was to assess the effect of the blockade of endothelin-1 (ET-1) receptor with ambrisentan on altered renal function induced by CP.

Aprepitant ameliorates vancomycin-induced kidney injury: Role of GPX4/system Xc and oxidative damage.

Vancomycin, a glycopeptide antibiotic, is used in cases of drug-resistant bacterial infections, but unfortunately is associated with acute kidney injury (AKI). We here explore the protective potential of aprepitant against vancomycin-induced AKI. Vancomycin (500 mg/kg/i.

Peficitinib halts acute kidney injury via JAK/STAT3 and growth factors immunomodulation.

Acute Kidney Injury (AKI) is characterized by a sudden loss of kidney function and its management continues to be a challenge. In this study the effect of peficitinib, a Janus kinase inhibitor (JAKi), was studied in an aim to stop the progression of AKI at an early point of injury. Adult male mice were injected with aristolochic acid (AA) a single dose (10 mg/kg, i.

Apocynin alleviates thioacetamide-induced acute liver injury: Role of NOX1/NOX4/NF-κB/NLRP3 pathways.

The liver has a distinctive capacity to regenerate, yet severe acute injury can be life-threatening if not treated appropriately. Inflammation and oxidative stress are central processes implicated in the pathophysiology of acute livery injury. NOX isoforms are important enzymes for ROS generation, NF-κB and NLRP3 activation, its inhibition could be vital in alleviating acute liver injury (ALI).

Roflumilast extenuates inflammation and oxidative stress in cadmium-induced hepatic and testicular injury in rats.

Roflumilast (ROF), a highly selective phosphodiesterase-4 inhibitor, has proven anti-inflammatory and immunomodulatory effects on the pulmonary system. However, the protective effects of ROF on cadmium (Cd)-induced hepatic and testicular injury has never been investigated. Adult male Sprague Dawley rats were acutely intoxicated with CdCl (3 mg/Kg, ip, qd, for 5 days).

Nifuroxazide mitigates doxorubicin-induced cardiovascular injury: Insight into oxidative/NLRP3/GSDMD-mediated pyroptotic signaling modulation.

Doxorubicin (DOX) is a widely used powerful anthracycline for treatment of many varieties of malignancies; however its cumulative and dose-dependent cardio-toxicity has been limited its clinical use. In the current study, in vivo and in vitro (neonatal rat's cardiomyocytes) experiments were conducted to identify the impact of nifuroxazide (NIFU) on DOX-induced cardiomyopathy, vascular injury, and hemato-toxcity and plot the underlying regulatory mechanisms. Cardiovascular injury was induced in vivo by I.

Empagliflozin enhances neuroplasticity in rotenone-induced parkinsonism: Role of BDNF, CREB and Npas4.

Aims: Parkinsonism is characterized by degeneration of dopaminergic neurons and impairment in neuroplasticity. Empagliflozin (EMPA) is an anti-diabetic drug that has been shown to improve cognitive dysfunctions and exerted antioxidant and anti-inflammatory effects in different models. This study aimed to determine the neuroprotective effects of EMPA against rotenone (ROT)-induced parkinsonism.

Hepatoprotective effect of nicorandil against acetaminophen-induced oxidative stress and hepatotoxicity in mice via modulating NO synthesis.

Acetaminophen (APAP) overdose can produce hepatotoxicity and consequently liver damage. This study investigated the hepatoprotective impacts of nicorandil on hepatic damage induced by APAP. Nicorandil was administered orally (100 mg/kg) for seven days before APAP challenge (500 mg/kg, ip).

Canagliflozin interrupts mTOR-mediated inflammatory signaling and attenuates DMBA-induced mammary cell carcinoma in rats.

Background: Breast cancer prevalence has been globally increasing, therefore, introducing novel interventions in cancer treatment is of a significant importance. The present study was designed to investigate the anti-cancer effect of Canagliflozin (CNG) in an experimental model of DMBA-induced mammary carcinoma in female rats.

Methods: 18 female rats were divided into three experimental groups: Normal control, DMBA control, DMBA+ CNG treated group.

The modulatory effect of sodium molybdate against cisplatin-induced CKD: Role of TGF-β/Smad signaling pathway.

Aims: Chronic kidney disease (CKD) is a global non-communicable health problem. Fibrosis is considered the base and the fate of CKD; thus, the goal of this study was to evaluate the effects of sodium molybdate on cisplatin-induced CKD model and demonstrate the possible involved mechanisms.

Materials And Methods: In cisplatin model, Wistar rats were challenged with cisplatin (1 mg/kg, i.

Anti-fibrotic activity of sitagliptin against concanavalin A-induced hepatic fibrosis. Role of Nrf2 activation/NF-κB inhibition.

Sitagliptin is known for its anti-diabetic activity though it has other pleiotropic pharmacological actions. Its effect against concanavalin A (Con A)-induced hepatic fibrosis has not been investigated yet. Our target was to test whether sitagliptin can suppress the development of Con A-induced hepatic fibrosis and if so, what are the mechanisms involved? Con A (6 mg/kg) was injected once weekly to male Swiss albino mice for four weeks.

Protective effects of paclitaxel on thioacetamide-induced liver fibrosis in a rat model.

Liver fibrosis is a public health burden that is highly associated with morbidity and mortality. Therefore, this study aims to explore the anti-fibrotic effects of low dose of paclitaxel (PTX) against thioacetamide (TAA)-induced liver fibrosis in rats and the possible mechanisms involved. TAA was administered at a dose of 200 mg/kg twice weekly for 6 weeks in rats to induce liver fibrosis similar to that in humans.

Chrysin mitigates bleomycin-induced pulmonary fibrosis in rats through regulating inflammation, oxidative stress, and hypoxia.

Pulmonary fibrosis is a chronic condition characterized by fibroblast proliferation, and the infiltration of inflammatory cells that can initiate local tissue hypoxia. In this study the effect of chrysin (50 mg/kg/orally) in a model of bleomycin (BLM)-induced pulmonary fibrosis was studied. Chrysin managed to decrease mortality rate associated with BLM instillation and it managed to improve lung architecture and lung fibrosis by decreasing hydroxyproline content and transforming growth factor-β1 (TGF-β1) protein expression.

Pirfenidone attenuates gentamicin-induced acute kidney injury by inhibiting inflammasome-dependent NLRP3 pathway in rats.

Acute kidney injury (AKI) is an abrupt and usually reversible decline in renal function. AKI is considered one of the main drawbacks of the use of gentamicin that critically limits its clinical use. In this study, pirfenidone, an oral antifibrotic drug, was given to rats (200 mg/kg, p.

Synthesis, in vivo anti-inflammatory, COX-1/COX-2 and 5-LOX inhibitory activities of new 2,3,4-trisubstituted thiophene derivatives.

New series of thiophene derivatives were synthesized and evaluated for their in vivo anti-inflammatory activity using carrageenan-induced paw edema model. The most active in vivo anti-inflammatory compounds 5b, 11b, 14c, 18c, 19c and 20d were further evaluated for their in vitro COX-1/COX-2 and 5-LOX inhibitory activities. The in vitro assay results revealed that the N-(4-(4-chlorophenyl)-3-cyanothiophen-2-yl)-2-morpholinoacetamide (5b) possesses the highest selectivity toward COX-2 (IC = 5.

Nicorandil ameliorates bleomycin-induced pulmonary fibrosis in rats through modulating eNOS, iNOS, TXNIP and HIF-1α levels.

Bleomycin (BLM) is one of the most common anti-cancer drugs used to treat numerous types of tumors. However, pulmonary toxicity is considered the most dramatic effect of BLM. Therefore, BLM has been frequently used for induction of pulmonary fibrosis.

Vitamin D3 abates BDL-induced cholestasis and fibrosis in rats via regulating Hedgehog pathway.

Liver cholestasis is a complex disease of broad etiologies. Hedgehog (Hh) signaling has been shown to play a pivotal role in modulating liver repair post cholestatic liver injury. We here investigated the role of vitamin D in experimental liver cholestasis induced by bile-duct ligation (BDL) in rats.

The dual PPAR-α/γ agonist saroglitazar ameliorates thioacetamide-induced liver fibrosis in rats through regulating leptin.

Liver fibrosis is a challenging global health problem resulting from chronic liver injury with no treatment currently available. It has been shown that activators for different peroxisome proliferator-activated receptor (PPAR) isoforms (α, γ, and δ) can affect different pathways in liver fibrosis. To evaluate the effects of the dual PPAR-α/γ agonist saroglitazar (SGZ) against thioacetamide (TAA)-induced fibrosis in rats, SGZ was administered for 6 weeks together with TAA injection.

Paclitaxel alleviates liver fibrosis induced by bile duct ligation in rats: Role of TGF-β1, IL-10 and c-Myc.

Liver fibrosis is a global health issue that causes morbidity and mortality with no currently available treatment. It has been shown that low dose paclitaxel (PTX) can stabilize microtubules and inhibit the profibrotic transforming growth factor-beta 1 (TGF-β1) signaling pathway. In this study the effect of treatment with low dose PTX was examined using a model of cholestatic liver fibrosis.

Agmatine attenuates rhabdomyolysis-induced acute kidney injury in rats in a dose dependent manner.

Acute kidney injury (AKI) is a serious disorder that accompanies rhabdomyolysis (RM). The underlying mechanisms as well as protective approaches need to be investigated. This study was targeted to explore the prophylactic effect of agmatine (AGM), an endogenous metabolite of l-arginine against RM-induced AKI.

Venlafaxine mitigates cisplatin-induced nephrotoxicity via down-regulating apoptotic pathway in rats.

The antidepressant venlafaxine, a norepinephrine and serotonin reuptake inhibitor, is recently identified for its anti-inflammatory role against many experimental models. In this study, the effect of venlafaxine against cisplatin-induced nephrotoxicity and bladder rings hypersensitivity towards acetylcholine were explored. Single injection of cisplatin (7 mg/kg, ip) in Sprague-Dawley rats instigated nephrotoxicity evidenced by hindering renal function (changes in kidney/body weight ratio, serum creatinine, BUN, albumin and urinary total protein levels which were supported by histopathology).

The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model.

Unlabelled: Vascular dysfunction leading to hypotension is a major complication in patients with septic shock. Inducible nitric oxide synthase (iNOS) together with oxidative stress play an important role in development of vascular dysfunction in sepsis. Searching for an endogenous, safe and yet effective remedy was the chief goal for this study.