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Anti-cytokine and anti-hyperalgesic effects of aliskiren in experimental models of inflammation


Rakesh B. Patel , Kanaiyalal D. Prajapati , Bhavin M. Sonara , Manoranjan M. Sharma , Vishwanath D. Pawar , Mukul R. Jain

Abstract

The renin‐angiotensin system is involved in pathogenesis and progression of inflammatory responses. In present study, we investigated the anti-cytokine and anti-hyperalgesic potential of aliskiren in LPS (lipopolysaccharide) and CFA (complete Freund’s adjuvant) induced inflammation in rodents. After aliskiren treatment, plasma cytokines (TNF-, IL-6) and plasma renin activity (PRA) were estimated in LPS treated mice. In CFA induced inflammatory pain model, rats were treated with aliskiren and thermal hyperalgesia was evaluated and TNF- and IL-6 were estimated in paw. In LPS treated ICR mice, elevated TNF- and IL-6 levels and PRA were attenuated by aliskiren. In LPS treated double transgenic mice (dTG), harboring human renin and human angiotensinogen and C57BL/6J mice, elevated TNF- level was inhibited by aliskiren. Moreover after LPS treatment, TNF- level was high (2.16 fold) in dTG mice than C57BL/6J. These data indicates that renin overexpression system in dTG mice is responsible for higher TNF- level suggests role of renin in inflammation. Moreover, Aliskiren showed anti-hyperalgesic activity in CFA induced inflammatory hyperalgesia in rats, which might be due to inhibition TNF- and IL- 6 levels, suggests the role of local renin in inflammation. Our results indicate the role of renin in experimental inflammation which is inhibited by aliskiren.



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