Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27069635
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Pharmacol+Res+Perspect
2016 ; 4
(2
): e00224
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological
profile of NOSH-naproxen (AVT-219) a dual NO- and H2S-releasing hybrid
#MMPMID27069635
Chattopadhyay M
; Kodela R
; Duvalsaint PL
; Kashfi K
Pharmacol Res Perspect
2016[Apr]; 4
(2
): e00224
PMID27069635
show ga
Naproxen (NAP) is a potent nonsteroidal anti-inflammatory drug (NSAID) with a
favorable cardiovascular profile. However, its long-term use may lead to serious
gastrointestinal and renal side effects. NOSH- (nitric oxide and hydrogen
sulfide) releasing naproxen (NOSH-NAP, AVT-219) belongs to a new class of
anti-inflammatory agents designed to overcome these limitations. We compared the
gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, and
antiplatelet properties of AVT-219 to that of NAP in preclinical animal models.
We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of
six different tissue origins and in a chemotherapeutic xenograft mouse model of
colon cancer. AVT-219: (1) was orders of magnitude more potent than NAP in
inhibiting the growth of cultured HCC; (2) was safe to the stomach, whereas NAP
caused significant ulceration; (3) showed strong anti-inflammatory, analgesic,
antipyretic, and antiplatelet properties comparable to NAP; and (4) NAP caused a
significant rise in plasma tumor necrosis factor-alpha (TNF?), whereas in the
AVT-219-treated rats this rise was significantly less. Mechanistically, AVT-219
was a strong antioxidant, inhibited cyclooxygenase (COX)-1 and -2, thus reducing
prostaglandin (PG) E2. In xenografts, AVT-219 significantly reduced tumor growth
and tumor mass with no sign of GI toxicity, whereas NAP-treated mice died due to
GI bleeding. AVT-219 displayed considerable safety and potency in inhibiting HCC
growth; was an effective analgesic, antipyretic, antiplatelet, and
anti-inflammatory; and was significantly more efficacious than NAP in reducing
the growth of established tumors in a xenograft mouse model.