主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Objectives. Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule. It is involved in homeostatic functions, such as blood pressure control, apoptosis, and regulates pathological mechanisms, including oxidative stress and inflammation. Acetaminophen (APAP) is most widely used as an analgesic and antipyretic drug. It is safe at therapeutic dosages but overdose of APAP can acute liver and kidney failure. In this study, protective effects of H2S against APAP-induced nephrotoxicity and the mechanisms of nephroprotective effects were investigated in rats.
Methods. Rats were divided into six group (n=7): Control (saline ip), APAP, APAP + NAC (N-acetyl sistein 140 mg/kg ip), APAP + NaHS (Sodium hydrosulfide, an H2S donor) (25, 50 and 100 micromol/kg ip). Nephrotoxicity was induced by the administration of a single dose of 2 g/kg APAP orally. After APAP administration rats were received NAC and NaHS for 7 consecutive days. KIM-1 (Kidney Injury Molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), TNF-alfa (Tumor necrosis factor-alfa), TGF-beta (Transforming growth factor-beta) were measured by ELISA in rat kidney homogenates. Tissue total oxidant status (TOS), and total antioxidant status (TAS) were evaluated spectrofotometrically. Apoptosis was assessed by TUNEL method. Glomerular and tubular structures were also examined histopathologically.
Results. Treatment with NaHS prevented APAP-induced nephrotoxicity as evidenced by significantly reduced KIM-1, NGAL, TNF-alfa, TGF-beta, TOS levels and increased TAS levels in rat kidney. NaHS was normalized the altered renal morphology and apoptosis. The benefical effects of NaHS on APAP-induced nephrotoxicity were similar to NAC. It was observed that the NaHS 25 and 50 micromol/kg doses revealed a more potent effect than the NaHS 100 micromol/kg dose.
Conclusions. These results suggest that H2S could reduce APAP-induced nephrotoxicity via anti-inflammatory, anti-oxidant, and anti-apoptotic effects.
