Effects of heme oxygenase 1 in the molecular changes and neuropathy associated with type 2 diabetes in mice
Por:
Pouso-Vázquez E., Bai X., Batallé G., Roch G., Pol O.
Publicada:
1 may 2022
Ahead of Print:
1 mar 2022
Resumen:
Painful diabetic neuropathy is one of the most common complications of diabetes in humans. The current treatments are not completely effective, and the main mechanisms implicated in the development of diabetic neuropathy are not completely elucidated. Thus, in male db/db mice, a murine model of type 2 diabetes, we investigated the effects of treatment with a heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), on the 1) hyperglycemia and mechanical allodynia associated with type 2 diabetes and 2) molecular changes induced by diabetic neuropathy in the central nervous system (CNS). Thus, we evaluated the effects of CoPP on the protein levels of 4-HNE (oxidative stress), Nrf2, superoxide dismutase 1 (SOD1), NAD(P)H quinone oxidoreductase 1 (NQO1), HO-1, glutathione S-transferase Mu 1 (GSTM1) (antioxidant enzymes), phosphatidylinositol 3-kinase/protein kinase B (nociceptive pathway), CD11b/c (microglial activation), and BAX (apoptosis) in the amygdala and spinal cord of db/db mice. Our results showed the antihyperglycemic and antiallodynic effects of CoPP treatment as well as the potent antioxidant, antinociceptive, anti-inflammatory, and antiapoptotic properties of this HO-1 inducer in the CNS of type 2 diabetic mice. Treatment with CoPP also prevented the downregulation of several antioxidant proteins (Nrf2, SOD-1, and NQO1) and/or enhanced the protein levels of HO-1 and GSTM1 in the spinal cord and/or amygdala of db/db mice. These effects might be implicated in the antiallodynic actions of CoPP. Our findings revealed the modulatory effects of CoPP in the CNS of db/db mice and provide new prospects for novel type 2 diabetes-associated neuropathy therapies.
Filiaciones:
Pouso-Vázquez E.:
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 08041, Spain
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, 08193, Spain
Bai X.:
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 08041, Spain
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, 08193, Spain
Batallé G.:
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 08041, Spain
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, 08193, Spain
Roch G.:
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 08041, Spain
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, 08193, Spain
Pol O.:
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, 08041, Spain
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, 08193, Spain
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