Doxycycline attenuates cisplatin-induced acute kidney injury through pleiotropic effects.

Doxycycline attenuates cisplatin-induced acute kidney injury through pleiotropic effects. Am J Physiol Renal Physiol. 2018 Jul 25;: Authors: Nakagawa T, Kakizoe Y, Iwata Y, Miyasato Y, Mizumoto T, Adachi M, Izumi Y, Kuwabara T, Suenaga N, Narita Y, Jono H, Saito H, Kitamura K, Mukoyama M Abstract Cisplatin (CDDP) is a widely-used chemotherapeutic drug for solid tumors, but its nephrotoxicity is a major dose-limiting factor. Doxycycline (Dox) is a tetracycline antibiotic that has been commonly used in a variety of infections. Dox has been shown to possess several other properties, including anti-tumor, anti-inflammatory, anti-oxidative, and matrix metalloproteinase (MMP)-inhibiting actions. We therefore investigated whether Dox exerts renoprotective effects in CDDP-induced acute kidney injury (AKI). Twelve-week-old male C57BL/6J mice were divided into the following groups: 1) Control, 2) Dox (2 mg/ml in drinking water), 3) CDDP (25 mg/kg body weight, intraperitoneally), and 4) CDDP+Dox. After 7 days of pretreatment with Dox, CDDP was administered and the animals were sacrificed at day 1 or 3. We evaluated renal function along with renal histological damage, inflammation, oxidative stress, and apoptosis. MMP and serine protease activities in the kidney tissues were assessed using zymography. Administration of CDDP exhibited renal dysfunction and caused histological damage predominantly in the proximal tubules. Dox did not affect either...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research