ABSTRACT
CONTEXT: This study aimed to evaluate the renoprotective action of linalool (LIN) on streptozotocin (STZ)-induced diabetic rats. OBJECTIVE: The pathological changes in diabetic nephropathy (DN) include oxidative stress, renal injury, matrix accumulation and podocyte abnormalities. We investigated the renoprotective actions of LIN, a monoterpene alcohol, present in herbal essential oils in STZ-induced diabetic rats with renal injury. MATERIALS AND METHODS: STZ-diabetic rats were administered LIN (25 mg/kg) for 45 days, after which the activities of key enzymes of glucose metabolism, collagen content, oxidative damage and expression of glucose transporter-1 (GLUT-1), transforming growth factor-ß1 (TGF-ß1), nuclear factor-κBp65 (NF-κB p65) and nephrin were analyzed. RESULTS: Diabetic rats displayed altered glucose metabolism, collagen accumulation and increased TGF-ß1 and NF-κB expression in kidney. LIN treatment restored glucose-metabolizing enzymes, collagen content and GLUT-1 expression and also prevented nephrin loss. LIN also rescued kidney from oxidative stress and inflammation by decreasing the expression of TGF-ß1 and NF-κB. Ultrastructural changes such as basement membrane thickening, reduction in podocyte number and loss of filtration barrier integrity in diabetic rats were mitigated by LIN. DISCUSSION AND CONCLUSION: The results of this study suggest that LIN can attenuate nephropathic changes induced in kidney of diabetic rats. These findings highlight the utility of LIN as a potential drug to treat renal damage in diabetic subjects.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/prevention & control , Extracellular Matrix/drug effects , Kidney/drug effects , Monoterpenes/therapeutic use , Podocytes/drug effects , Acyclic Monoterpenes , Animals , Anti-Inflammatory Agents/administration & dosage , Biomarkers/metabolism , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/immunology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Extracellular Matrix/immunology , Extracellular Matrix/metabolism , Kidney/immunology , Kidney/metabolism , Kidney/ultrastructure , Male , Microscopy, Electron, Transmission , Monoterpenes/administration & dosage , Podocytes/pathology , Rats , Rats, Wistar , Streptozocin/pharmacologyABSTRACT
SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.