Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats

Nilesh M. Kalariya, Mohammad Shoeb, Naseem Ansari, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

PURPOSE. To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxininduced uveitis (EIU) in rats. METHODS. EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 μg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction. Three and 24 hours after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK, and NF-κB (p65) were determined immunohistochemically. Primary human nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin. RESULTS. Compared with controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media. CONCLUSIONS. Our results for the first time demonstrate a novel role of the antidiabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.

Original languageEnglish (US)
Pages (from-to)3431-3440
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number7
DOIs
StatePublished - Jun 2012

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Metformin
Uveitis
Hypoglycemic Agents
Endotoxins
AMP-Activated Protein Kinases
Aqueous Humor
Cytokines
Chemokines
Epithelial Cells
Phosphorylation
Ciliary Body
Interleukin-18
NF-kappa B
Therapeutic Uses
Subcutaneous Injections
Leptin
Interleukin-1
Dinoprostone
Culture Media
Lipopolysaccharides

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats. / Kalariya, Nilesh M.; Shoeb, Mohammad; Ansari, Naseem; Srivastava, Satish; Ramana, Kota.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 7, 06.2012, p. 3431-3440.

Research output: Contribution to journalArticle

Kalariya, Nilesh M. ; Shoeb, Mohammad ; Ansari, Naseem ; Srivastava, Satish ; Ramana, Kota. / Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 7. pp. 3431-3440.
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abstract = "PURPOSE. To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxininduced uveitis (EIU) in rats. METHODS. EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 μg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction. Three and 24 hours after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK, and NF-κB (p65) were determined immunohistochemically. Primary human nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin. RESULTS. Compared with controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media. CONCLUSIONS. Our results for the first time demonstrate a novel role of the antidiabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.",
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N2 - PURPOSE. To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxininduced uveitis (EIU) in rats. METHODS. EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 μg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction. Three and 24 hours after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK, and NF-κB (p65) were determined immunohistochemically. Primary human nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin. RESULTS. Compared with controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media. CONCLUSIONS. Our results for the first time demonstrate a novel role of the antidiabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.

AB - PURPOSE. To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxininduced uveitis (EIU) in rats. METHODS. EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 μg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction. Three and 24 hours after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK, and NF-κB (p65) were determined immunohistochemically. Primary human nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin. RESULTS. Compared with controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media. CONCLUSIONS. Our results for the first time demonstrate a novel role of the antidiabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.

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