Synergistic effects of telmisartan and pyridoxamine on early renal damage             in spontaneously hypertensive rats.
The aim of this study was to investigate the protective effects of telmisartan and/or pyridoxamine on spontaneously hypertensive rats (SHRs). Rats were treated with telmisartan (T group) or pyridoxamine (P group), or telmisartan and pyridoxamine (TP group). The serum levels of advanced glycation end products (AGEs), superoxide dismutase (SOD), malonaldehyde and the level of 24-h urinary albumin were measured. Morphological changes in renal tissues were observed under light (H&E or Masson's trichrome) and transmission electron microscopy. Expression of NF-κBp65 and p-ERK1/2 in renal tissue was detected by immunohistochemistry. Expression of receptors for advanced glycation end products (RAGE) and TGF-β in the renal cortex was investigated by western blotting. We found that early renal structural and functional damage was alleviated in the three intervention groups. SOD activity was significantly elevated in the P and TP groups (P<0.05) compared to that in the T group. Of note, both the positive expression of NF-κBp65 (P<0.01 vs. the T and P groups) and p-ERK1/2 (P<0.05 vs. the P group) was lowest in the TP group. Our results suggest that the combined use of telmisartan and pyridoxamine is superior to the single use of either drug on renoprotection, which may result from the alleviation of oxidative stress and the reduction of NF-κBp65 and p-ERK1/2 activation.
Department of Geriatrics, Fujian Provincial Hospital, Fujian Institute of Clinical Geriatrics, Fujian Medical University, Fuzhou, Fujian 350001, PR China. zhu_pengli@yahoo.cn
Pengli
P
Zhu
Hong
H
Lin
Chengai
C
Sun
Fan
F
Lin
Huizhen
H
Yu
Xiuping
X
Zhuo
Chanjuan
C
Zhou
Zhisheng
Z
Deng
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D004357:Drug Synergism; D017127:Glycation End Products, Advanced / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000097:blood; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011733:Pyridoxamine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D000077333:Telmisartan; D051996:Transcription Factor RelA / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001562:Benzimidazoles; D001565:Benzoates; D017127:Glycation End Products, Advanced; D020011:Protective Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D008315:Malondialdehyde; D011733:Pyridoxamine; D013482:Superoxide Dismutase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077333:Telmisartan