3-nitrotyrosine and genipin

Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1. In addition, GP attenuated the CP-induced oxidative/nitrative stress by suppressing the activation of NADPH oxidase, augmenting the endogenous antioxidant defense system, and diminishing the accumulation of 4-hydroxynonenal and 3-nitrotyrosine in renal tissues. Furthermore, reduced levels of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta indicated that CP-induced renal inflammation was mitigated upon the treatment with GP. GP also attenuated the CP-induced activation of mitogen-activated protein kinases, excessive activities of caspase-3/7 and poly(ADP-ribose) polymerase, DNA fragmentation, and apoptosis. When administered 12h after the onset of kidney injury, GP showed a therapeutic effect by ameliorating CP-induced nephrotoxicity. Moreover, GP synergistically enhanced the CP-induced cell death of T24 human bladder cancer cells. Collectively, our data indicate that GP attenuated the CP-induced renal tissue injury by abrogating oxidative/nitrative stress and inflammation and by blocking cell death pathways, thereby improving the renal function. Thus, our results suggest that the use of GP may be a promising new protective strategy against cisplatin-induced nephrotoxicity.

Topics: Aldehydes; Animals; Antioxidants; Apoptosis; Blood Urea Nitrogen; Caspase 3; Caspase 7; Cell Line, Tumor; Cisplatin; Creatinine; Cystatin C; Cytokines; Hepatitis A Virus Cellular Receptor 1; Humans; Inflammation; Iridoids; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Oxidative Stress; Poly(ADP-ribose) Polymerases; Tyrosine

To investigate the beneficial effects of inchinkoto (ICKT) in the liver after 70% hepatectomy following ischemia reperfusion.. Wistar rats were divided into 3 groups: simple laparotomy and 70% hepatectomy (Hx), 70% hepatectomy following ischemia reperfusion (IR) with vehicle (IRHxV), 70% hepatectomy following IR with ICKT (1 or 2 g/kg of body weight; IRHxK). Vehicle or ICKT was administered for 3 days preoperatively. The hepatoduodenal ligament was clamped for 15 minutes before hepatectomy in the IRHx groups. Rats were killed 1 hours after hepatectomy. In other experiments, the hepatoduodenal ligament was clamped for 30 minutes, with or without ICKT treatment, to evaluate the effect of ICKT on IR injury-induced mortality. Serum transaminase levels and the gene expression of inflammatory cytokines and inducible nitric oxide synthase in the remnant liver were determined. Furthermore, the expression of antioxidant genes was evaluated by PCR array.. The elevation of serum transaminase levels, the upregulation of genes for inflammatory cytokines and inducible nitric oxide synthase, and the increased formation of nitrotyrosine observed in the remnant livers of the IRHxV group were all significantly attenuated by preoperative administration of ICKT in the IRHxK group. The expression of antioxidant genes was also higher in the IRHxK group compared with that of the IRHxV group. Moreover, administration of ICKT significantly reduced the mortality induced by IRHx after 30-minute ischemia.. Preoperative administration of ICKT provides beneficial effects through attenuating inflammatory responses and oxidative stress in the liver following IR and subsequent hepatectomy.

Topics: Animals; Antioxidants; Cytokines; Drugs, Chinese Herbal; Glutathione; Hepatectomy; Inflammation Mediators; Iridoid Glycosides; Iridoids; Liver; Male; Nitric Oxide Synthase; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Polymerase Chain Reaction; Rats; Rats, Wistar; Reactive Nitrogen Species; Reactive Oxygen Species; Reperfusion Injury; Survival Rate; Transaminases; Tyrosine

Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However, whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.. The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.. Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.. UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

Topics: Animals; Cells, Cultured; Glucagon; Glucagon-Secreting Cells; Insulin; Insulin Receptor Substrate Proteins; Ion Channels; Iridoid Glycosides; Iridoids; Mice; Mitochondrial Proteins; Oxidative Stress; Palmitic Acid; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphorylation; RNA, Messenger; Signal Transduction; Trans-Activators; Transcription Factors; Tyrosine; Uncoupling Protein 2