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A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo.

Ge X, Feng Z, Xu T, Wu B, Chen H, Xu F, Fu L, Shan X, Dai Y, Zhang Y, Liang G - Drug Des Devel Ther (2016)

Bottom Line: In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity.We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability.Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences; Department of Pulmonary Medicine, The 2nd Affiliated Hospital.

ABSTRACT
Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

No MeSH data available.


Related in: MedlinePlus

X22 attenuated LPS-induced septic shock in vivo.Notes: (A) Male ICR mice were injected intravenously with vehicle or X22 (25 and 50 mg/kg) and the body weight was recorded for 7 days. (B) Male C57BL/6 mice were pretreated with X22 (tail vein injection, 20 mg/kg) or vehicle, followed by injection of LPS (tail vein injection, 20 mg/kg). Survival rates were recorded for 7 days at an interval of 24 hours after the LPS injection. n=10 animals in each group. **P<0.01 versus LPS group.Abbreviations: CON, control; ICR mice, Institute of Cancer Research mice; LPS, lipopolysaccharide.
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f4-dddt-10-1947: X22 attenuated LPS-induced septic shock in vivo.Notes: (A) Male ICR mice were injected intravenously with vehicle or X22 (25 and 50 mg/kg) and the body weight was recorded for 7 days. (B) Male C57BL/6 mice were pretreated with X22 (tail vein injection, 20 mg/kg) or vehicle, followed by injection of LPS (tail vein injection, 20 mg/kg). Survival rates were recorded for 7 days at an interval of 24 hours after the LPS injection. n=10 animals in each group. **P<0.01 versus LPS group.Abbreviations: CON, control; ICR mice, Institute of Cancer Research mice; LPS, lipopolysaccharide.

Mentions: The body weight of the X22-treated groups (25 and 50 mg/kg, tail vein injection) was not different from that of the control group (Figure 4A), which indicates that X22, even at the high dose of 50 mg/kg, is not toxic in mice. Male C57BL/6 mice injected with LPS (20 mg/kg) in the presence of X22 pretreatment (tail vein injection) were monitored for 7 days to assess their survival rates. The data presented in Figure 4B revealed that LPS alone caused 80% of mice death within 48 hours, whereas pretreatment with X22 at 20 mg/kg prior to LPS injection significantly improved the survival rate compared with the LPS-treated group alone.


A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo.

Ge X, Feng Z, Xu T, Wu B, Chen H, Xu F, Fu L, Shan X, Dai Y, Zhang Y, Liang G - Drug Des Devel Ther (2016)

X22 attenuated LPS-induced septic shock in vivo.Notes: (A) Male ICR mice were injected intravenously with vehicle or X22 (25 and 50 mg/kg) and the body weight was recorded for 7 days. (B) Male C57BL/6 mice were pretreated with X22 (tail vein injection, 20 mg/kg) or vehicle, followed by injection of LPS (tail vein injection, 20 mg/kg). Survival rates were recorded for 7 days at an interval of 24 hours after the LPS injection. n=10 animals in each group. **P<0.01 versus LPS group.Abbreviations: CON, control; ICR mice, Institute of Cancer Research mice; LPS, lipopolysaccharide.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930233&req=5

f4-dddt-10-1947: X22 attenuated LPS-induced septic shock in vivo.Notes: (A) Male ICR mice were injected intravenously with vehicle or X22 (25 and 50 mg/kg) and the body weight was recorded for 7 days. (B) Male C57BL/6 mice were pretreated with X22 (tail vein injection, 20 mg/kg) or vehicle, followed by injection of LPS (tail vein injection, 20 mg/kg). Survival rates were recorded for 7 days at an interval of 24 hours after the LPS injection. n=10 animals in each group. **P<0.01 versus LPS group.Abbreviations: CON, control; ICR mice, Institute of Cancer Research mice; LPS, lipopolysaccharide.
Mentions: The body weight of the X22-treated groups (25 and 50 mg/kg, tail vein injection) was not different from that of the control group (Figure 4A), which indicates that X22, even at the high dose of 50 mg/kg, is not toxic in mice. Male C57BL/6 mice injected with LPS (20 mg/kg) in the presence of X22 pretreatment (tail vein injection) were monitored for 7 days to assess their survival rates. The data presented in Figure 4B revealed that LPS alone caused 80% of mice death within 48 hours, whereas pretreatment with X22 at 20 mg/kg prior to LPS injection significantly improved the survival rate compared with the LPS-treated group alone.

Bottom Line: In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity.We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability.Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences; Department of Pulmonary Medicine, The 2nd Affiliated Hospital.

ABSTRACT
Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

No MeSH data available.


Related in: MedlinePlus